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A number sign (#) is used with this entry because of evidence that distal hereditary motor neuronopathy type IX (HMN9) is caused by heterozygous mutation in the WARS gene (WARS1; 191050) on chromosome 14q32. Description HMN9 is an autosomal dominant neurologic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy affecting both the lower and upper limbs (summary by Tsai et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN, see HMN type I (HMN1; 182960). Clinical Features Tsai et al. (2017) reported 9 individuals from 2 unrelated Taiwanese families and a patient from a Belgian family with HMN9. Clinical evaluation was available for 7 patients. The patients presented with slowly progressive, distal predominant, pure motor neuropathy between 9 and 13 years of age (juvenile onset). Features included muscle weakness and atrophy in the feet and legs, followed by hand muscle involvement. All were able to ambulate without assistance, except 1 patient, who became wheelchair-bound in his fifties. Affected individuals had high-arched feet, thin lower legs, hypo- or areflexia, and variable degrees of hand muscle weakness and atrophy. Two older individuals had profound atrophy and paralysis of the intrinsic hand muscles. None of the patients had subjective sensory complaints, and nerve conduction studies showed a pure motor axonal neuropathy. Sural nerve biopsy of the Belgian woman showed a normal pattern, and muscle biopsy was compatible with neurogenic atrophy. The Belgian woman's father and younger brother were reported to have had a similar disorder, but they were both deceased at the time of evaluation. The Belgian woman died at age 66 due to an unrelated illness. Inheritance The transmission pattern of distal hereditary motor neuronopathy in the families reported by Tsai et al. (2017) was consistent with autosomal dominant inheritance. Molecular Genetics In 7 affected individuals from 2 unrelated Taiwanese families and in a Belgian woman with HMN9, Tsai et al. (2017) identified a heterozygous missense mutation in the WARS gene (H257R; 191050.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing in the first family, segregated with the disorder in all the families. The mutation in the second Taiwanese family was found by screening of the WARS gene in 79 additional Taiwanese individuals with a similar disorder; haplotype analysis indicated that the mutation arose independently in these 2 families. The mutation in the Belgian family was found after screening the WARS gene in 163 unrelated index cases with a similar disorder from various populations. In vitro functional expression studies in HEK293 cells showed that the mutation resulted in decreased WARS aminoacylation activity and compromised protein synthesis in a dominant-negative manner. The mutant protein was able to form dimers with wildtype WARS, which may explain the dominant-negative effect. Knockdown of WARS using siRNA resulted in decreased cell viability that could not be rescued by expression of mutant WARS. Neuronal cells transfected with the mutation showed decreased neurite outgrowth and neurite degeneration compared to controls, and rat motor neurons expressing the mutation showed evidence of impaired axonal transport. The mutant protein also showed enhanced interaction with VE-cadherin (see, e.g., CDH5, 601120), resulting in augmented angiostatic activity in human vascular endothelial cells. The findings indicated that the mutation alters the canonical and noncanonical functions of TrpRS. INHERITANCE \- Autosomal dominant SKELETAL Feet \- Pes cavus NEUROLOGIC Peripheral Nervous System \- Muscle weakness, distal, upper and lower limbs, due to neuropathy \- Muscle atrophy, distal, upper and lower limbs, due to neuropathy \- Atrophy of the intrinsic hand muscles \- Hyporeflexia \- Motor axonal neuropathy \- Difficulty walking MISCELLANEOUS \- Juvenile onset (range 9 to 13 years) \- Slowly progressive \- Lower limb involvement usually precedes upper limb involvement MOLECULAR BASIS \- Caused by mutation in the tryptophanyl-tRNA synthetase 1 gene (WARS1, 191050.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IX

c4540265

omim

https://www.omim.org/entry/617721

{"omim": ["617721"], "synonyms": ["Alternative titles", "NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE IX"]}

## Clinical Features Van Steensel et al. (2002) reported a mother and daughter with a syndrome of hypotrichosis, striate palmoplantar keratoderma, onychogryphosis, periodontitis, acroosteolysis, and psoriasis-like skin lesions. The syndrome resembled Papillon-Lefevre syndrome (245000), characterized by palmoplantar keratoderma, periodontitis, and psoriasis-like skin lesions, and particularly Haim-Munk syndrome (245010), an allelic variant of Papillon-Lefevre with acroosteolysis. Both are caused by mutations in the cathepsin C gene (602365). The patients reported by Van Steensel et al. (2002) differed in the nature of the palmar keratoderma and hypotrichosis. Additionally, they lacked the pes planus seen in Haim-Munk syndrome. The proband had dystrophic nails and absent eyebrows and lashes since birth, with thickened palmoplantar skin since the age of 2 years. At age 7 years, her scalp hair, which had always been thinly implanted, started to fall out; hair loss was not accompanied by other symptoms such as pustules, itching, or scaling. Cutting her strongly curved nails was nearly impossible, as it was very painful and accompanied by bleeding. Around the same time, her teeth began to be affected by caries, and periodontitis became apparent. At about 15 years of age, erythematous scaly lesions appeared on the lower arms and legs. Electron microscopic examination of the hair showed pili torti et annulati. At age 27, both hands showed significant onychogryphosis with several fingers apparently lacking distal phalanges. All digits were thin and tapered towards the tips. At age 52, peculiar, reticulate pitted hyperkeratosis of the palms, spiky hyperkeratosis of the soles, hypotrichosis universalis, and lingua plicata were noted. The hypotrichosis of the scalp seemed secondary to scarring alopecia, as hair follicle openings were missing over most of the scalp. The hyperkeratosis of the palms was highly unusual, following a reticular pattern and showing many small 'pinprick' pits. She developed ventricular tachycardia in the fifth decade of life. The proband had an affected daughter who developed nail abnormalities at age 3 months. Hyperkeratoses of the feet appeared at age 2 years. At the age of 13 years, she developed joint pains. Periarticular bone density was decreased, suggesting that the daughter, too, might be suffering from osteolysis. Physical examination showed onychogryphosis, hypotrichosis, periodontitis, and lingua plicata. She also had palmoplantar keratoderma, but in her case the palmar keratoderma was nummular rather than linear. The plantar keratoderma was similar to that seen in her mother. She had erythematous, scaling lesions on the lower arms and legs. The hypotrichosis and periodontitis were less severe than in the mother. Histology of a skin biopsy from a hyperkeratotic area from the mother showed pronounced orthohyperkeratosis but no other abnormalities. The biopsy from a psoriasis-like region on the leg showed hyperplasia and hyperparakeratosis. The granular layer was absent. The dermal papillae were elongated but did not show the tongue shape typical for psoriasis. In the upper dermis, there was a perivascular lymphocytic infiltrate. A biopsy slide of the daughter showed identical abnormalities. Examination of a scalp biopsy showed a reduced number of hair follicles and only slight scarring. The mode of inheritance could not be determined unambiguously as there were only 2 affected individuals, but an autosomal dominant mode was considered most likely. Molecular Genetics Van Steensel et al. (2002) sequenced the CTSC gene in the proband and found no mutations in either coding or noncoding parts of the gene. They proposed that their patients suffered from a theretofore undescribed syndrome possibly caused by mutations in a gene that has a functional or structural relation with CTSC. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

HYPOTRICHOSIS-OSTEOLYSIS-PERIODONTITIS-PALMOPLANTAR KERATODERMA SYNDROME

c1843285

omim

https://www.omim.org/entry/607658

{"mesh": ["C564357"], "omim": ["607658"], "orphanet": ["307936"], "synonyms": ["Alternative titles", "HOPP SYNDROME"]}

An aggressive soft tissue cancer that typically arises in serous lined surfaces of the abdominal or pelvic peritoneum, and spreads to the omentum, lymph nodes and hematogenously disseminates especially to the liver. Extraserous primary location has been reported in exceptional cases. ## Epidemiology DSRCT is extremely rare. Only a few hundred cases have been reported worldwide since the first description in 1989. It usually affects males, during adolescence or young adulthood, with a male-to-female ratio of 4:1. ## Clinical description Clinical signs and symptoms of DSRCT are non-specific. DSRCT presents with abdominal pain, enlarged abdomen, dyspepsia, and/or vomiting and weight loss depending on the stage of the disease. Other signs can be observed such as a palpable abdominal mass, gastrointestinal occlusion, ascites, and hepatomegaly. Sometimes, DSRCT can arise from other primary sites such as the brain, thorax, lung, paratesticular region, ovaries and nasal cavity, without characteristic clinical signs. ## Etiology DSRCT seems to originate from the mesothelium. In almost all cases, a specific translocation t(11;22)(p13;q12) is found that juxtaposes the EWSR1 gene to the WT1 tumor suppressor gene. However, the underlying molecular mechanism remains unknown. Several other associated chromosomal translocations have been described (t(5;19), t(X;16) and t(4;10)). ## Diagnostic methods The diagnosis is difficult due to the rarity of the tumor and its similarities with other small round cell tumors. Diagnosis is based on clinical signs, endoscopic examination (laparoscopy) and/or imaging techniques (radiography, chest-abdominal-pelvic computed tomography (CAP-CT)). Biopsy of the mass shows nests of poorly differentiated small round cells with little cytoplasm and hyperchromatic nuclei that are surrounded by desmoplastic stroma. Cells can present an epithelial, mesenchymal, or neuronal differentiation. The diagnosis is confirmed by the presence of a polyphenotypic immunoprofile (tumor cells express several cytokeratins (KL1, AE1/AE3), desmin, and neuron-specific enolase), and by molecular identification (FISH, RT-PCR) of the EWSR1/WT1 translocation. ## Differential diagnosis Differential diagnoses include all the small round cells tumors: Ewing sarcoma and other peripheral neuroectodermal tumors (PNET), Wilms tumor, rhabdomyosarcoma and undifferentiated carcinoma (see these terms). ## Management and treatment Management is multidisciplinary and must be discussed by a panel of physicians in a specialized center. Up to 30% of DSRCT cases are misdiagnosed leading to incorrect management. There are currently no validated recommendations on clinical management and no cytotoxic agents have been granted a European Marketing Authorization (MA) in this indication. Some teams have proposed treatment based on aggressive multiagent chemotherapy (off-label use), followed by optimal cytoreductive surgery and abdominal radiotherapy. Prospective studies are underway to evaluate the effect of hyperthermic intraperitoneal chemotherapy (HIPEC), maintenance chemotherapy and targeted therapy. ## Prognosis Prognosis is poor. Median overall survival is 17 months and less than 20% of patients live more than 5 years after diagnosis. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Desmoplastic small round cell tumor

c0281508

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83469

{"gard": ["6265"], "mesh": ["D058405"], "umls": ["C0281508"], "icd-10": ["C48.2"], "synonyms": ["DSRCT"]}

Gastric volvulus Other namesVolvulus of stomach SpecialtyGeneral surgery Gastric volvulus or volvulus of stomach is a twisting of all or part of the stomach by more than 180 degrees with obstruction of the flow of material through the stomach, variable loss of blood supply and possible tissue death. The twisting can occur around the long axis of the stomach: this is called organoaxial or around the axis perpendicular to this, called mesenteroaxial. Obstruction is more likely in organoaxial twisting than with mesenteroaxial while the latter is more associated with ischemia. About one third of the cases are associated with a hiatus hernia. Treatment is surgical. The classic triad (Borchardt's Triad) of gastric volvulus, described by Borchardt in 1904, consists of severe epigastric pain, retching (due to sour taste in mouth) without vomiting, inability to pass a nasogastric tube and reportedly occurs in 70% of cases. Sometimes severe pain at the top of left shoulder, this may be due to internal bleeding irritating the diaphragm upon respiration. ## Contents * 1 Classification * 1.1 Organoaxial type * 1.2 Mesenteroaxial type * 1.3 Combined type * 2 Cause * 2.1 Type 1 * 2.2 Type 2 * 3 Diagnosis * 3.1 Upper GI studies * 3.2 Endoscopy * 4 References * 5 External links ## Classification[edit] ### Organoaxial type[edit] In an organoaxial gastric volvulus, the stomach rotates around an axis that connects the gastroesophageal junction and the pylorus. The antrum rotates in opposite direction to the fundus of the stomach. This is the most common type of gastric volvulus, occurring in approximately 59% of cases, and it is usually associated with diaphragmatic defects. Strangulation and necrosis commonly occur with organoaxial gastric volvulus and have been reported in 5–28% of cases. The key imaging feature of organoaxial volvulus is that the greater curvature is located above the lesser curvature of the stomach.[1] ### Mesenteroaxial type[edit] The mesenteroaxial axis bisects the lesser and greater curvatures. The antrum rotates anteriorly and superiorly so that the posterior surface of the stomach lies anteriorly. The rotation is usually incomplete and occurs intermittently. Vascular compromise is uncommon. This cause comprises approximately 29% of cases of gastric volvulus. The key imaging feature of mesenteroaxial volvulus is that the antrum is above the gastroesophageal junction.[1] ### Combined type[edit] The combined type of gastric volvulus is a rare form in which the stomach twists mesentericoaxially and organoaxially. This type of gastric volvulus makes up the remainder of cases and is usually observed in patients with chronic volvulus. ## Cause[edit] ### Type 1[edit] Gastric volvulus of unknown cause comprises two thirds of cases and is presumably due to abnormal laxity of the gastrosplenic, gastroduodenal, gastrophrenic, and gastrohepatic ligaments. Type 1 gastric volvulus is more common in adults but has been reported in children. ### Type 2[edit] Type 2 gastric volvulus is found in one third of patients and is usually associated with congenital or acquired abnormalities that result in abnormal mobility of the stomach. ## Diagnosis[edit] On chest radiography, a retrocardiac, gas-filled viscus may be seen in cases of intrathoracic stomach, which confirms the diagnosis. Plain abdominal radiography reveals a massively distended viscus in the upper abdomen. In organoaxial volvulus, plain films may show a horizontally oriented stomach with a single air-fluid level and a paucity of distal gas. In mesenteroaxial volvulus, plain abdominal radiographic findings include a spherical stomach on supine images and 2 air-fluid levels on erect images, with the antrum positioned superior to the fundus. ### Upper GI studies[edit] The diagnosis of gastric volvulus is usually based on barium studies; however, some authors recommend computed tomography (CT) scanning as the imaging modality of choice. Upper gastrointestinal (GI) contrast radiographic studies (using barium or Gastrografin) are sensitive and specific if performed with the stomach in the "twisted" state and may show an upside-down stomach. Contrast studies have been reported to have a diagnostic yield in 81–84% of patients. Often performed for an evaluation of acute abdominal pain, a computed tomography (CT) scan can offer immediate diagnosis by showing two bubbles with a transition line. Proponents of CT scanning in the diagnosis of gastric volvulus report several benefits, including: 1. the ability to rapidly diagnose the condition based on a few coronal reconstructed images, 2. the ability to detect the presence or absence of gastric pneumatosis and free air, 3. the detection of predisposing factors (i.e., diaphragmatic or hiatal hernias), and 4. the exclusion of other abdominal pathology. ### Endoscopy[edit] Upper gastrointestinal (GI) endoscopy may be helpful in the diagnosis of gastric volvulus. When this procedure reveals distortion of the gastric anatomy with difficulty intubating the stomach or pylorus, it can be highly suggestive of gastric volvulus. In the late stage of gastric volvulus, strangulation of the blood supply can result in progressive ischemic ulceration or mucosal fissuring. The nonoperative mortality rate for gastric volvulus is reportedly as high as 80%. Historically, mortality rates of 30–50% have been reported for acute gastric volvulus, with the major cause of death being strangulation, which can lead to necrosis and perforation. With advances in diagnosis and management, the mortality rate from acute gastric volvulus is 15–20% and that for chronic gastric volvulus is 0–13%. ## References[edit] 1. ^ a b Carter, R; Brewer LA, 3rd; Hinshaw, DB (July 1980). "Acute gastric volvulus. A study of 25 cases". American Journal of Surgery. 140 (1): 99–106. doi:10.1016/0002-9610(80)90424-9. PMID 7396092. ## External links[edit] Classification D * ICD-10: K31.8 * ICD-9-CM: 537.89 * MeSH: D013277 * DiseasesDB: 32054 External resources * eMedicine: med/2714 radio/296 * Schaefer D, Nikoomenesh P, Moore C (1997). "Gastric volvulus: an old disease process with some new twists". Gastroenterologist. 5 (1): 41–5. PMID 9074918. * v * t * e Diseases of the digestive system Upper GI tract Esophagus * Esophagitis * Candidal * Eosinophilic * Herpetiform * Rupture * Boerhaave syndrome * Mallory–Weiss syndrome * UES * Zenker's diverticulum * LES * Barrett's esophagus * Esophageal motility disorder * Nutcracker esophagus * Achalasia * Diffuse esophageal spasm * Gastroesophageal reflux disease (GERD) * Laryngopharyngeal reflux (LPR) * Esophageal stricture * Megaesophagus * Esophageal intramural pseudodiverticulosis Stomach * Gastritis * Atrophic * Ménétrier's disease * Gastroenteritis * Peptic (gastric) ulcer * Cushing ulcer * Dieulafoy's lesion * Dyspepsia * Pyloric stenosis * Achlorhydria * Gastroparesis * Gastroptosis * Portal hypertensive gastropathy * Gastric antral vascular ectasia * Gastric dumping syndrome * Gastric volvulus * Buried bumper syndrome * Gastrinoma * Zollinger–Ellison syndrome Lower GI tract Enteropathy Small intestine (Duodenum/Jejunum/Ileum) * Enteritis * Duodenitis * Jejunitis * Ileitis * Peptic (duodenal) ulcer * Curling's ulcer * Malabsorption: Coeliac * Tropical sprue * Blind loop syndrome * Small bowel bacterial overgrowth syndrome * Whipple's * Short bowel syndrome * Steatorrhea * Milroy disease * Bile acid malabsorption Large intestine (Appendix/Colon) * Appendicitis * Colitis * Pseudomembranous * Ulcerative * Ischemic * Microscopic * Collagenous * Lymphocytic * Functional colonic disease * IBS * Intestinal pseudoobstruction / Ogilvie syndrome * Megacolon / Toxic megacolon * Diverticulitis/Diverticulosis/SCAD Large and/or small * Enterocolitis * Necrotizing * Gastroenterocolitis * IBD * Crohn's disease * Vascular: Abdominal angina * Mesenteric ischemia * Angiodysplasia * Bowel obstruction: Ileus * Intussusception * Volvulus * Fecal impaction * Constipation * Diarrhea * Infectious * Intestinal adhesions Rectum * Proctitis * Radiation proctitis * Proctalgia fugax * Rectal prolapse * Anismus Anal canal * Anal fissure/Anal fistula * Anal abscess * Hemorrhoid * Anal dysplasia * Pruritus ani GI bleeding * Blood in stool * Upper * Hematemesis * Melena * Lower * Hematochezia Accessory Liver * Hepatitis * Viral hepatitis * Autoimmune hepatitis * Alcoholic hepatitis * Cirrhosis * PBC * Fatty liver * NASH * Vascular * Budd–Chiari syndrome * Hepatic veno-occlusive disease * Portal hypertension * Nutmeg liver * Alcoholic liver disease * Liver failure * Hepatic encephalopathy * Acute liver failure * Liver abscess * Pyogenic * Amoebic * Hepatorenal syndrome * Peliosis hepatis * Metabolic disorders * Wilson's disease * Hemochromatosis Gallbladder * Cholecystitis * Gallstone / Cholelithiasis * Cholesterolosis * Adenomyomatosis * Postcholecystectomy syndrome * Porcelain gallbladder Bile duct/ Other biliary tree * Cholangitis * Primary sclerosing cholangitis * Secondary sclerosing cholangitis * Ascending * Cholestasis/Mirizzi's syndrome * Biliary fistula * Haemobilia * Common bile duct * Choledocholithiasis * Biliary dyskinesia * Sphincter of Oddi dysfunction Pancreatic * Pancreatitis * Acute * Chronic * Hereditary * Pancreatic abscess * Pancreatic pseudocyst * Exocrine pancreatic insufficiency * Pancreatic fistula Other Hernia * Diaphragmatic * Congenital * Hiatus * Inguinal * Indirect * Direct * Umbilical * Femoral * Obturator * Spigelian * Lumbar * Petit's * Grynfeltt-Lesshaft * Undefined location * Incisional * Internal hernia * Richter's Peritoneal * Peritonitis * Spontaneous bacterial peritonitis * Hemoperitoneum * Pneumoperitoneum *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Gastric volvulus

c0038359

wikipedia

https://en.wikipedia.org/wiki/Gastric_volvulus

{"mesh": ["D013277"], "icd-9": ["537.89"], "icd-10": ["K31.8"], "wikidata": ["Q5526795"]}

Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome is a rare, genetic, mitochondrial disease characterized by early-onset progressive renal failure, manifesting with hyperuricemia, hyponatremia, hypomagnesemia, hypochloremic metabolic alkalosis, elevated BUN and polyuria, associated with systemic manifestations which include pulmonary hypertension, failure to thrive, global developmental delay, hypotonia and ventricular hypertrophy. Additional features include prematurity, elevated serum lactate, diabetes mellitus and, in some, pancytopenia. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome

c3151209

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363694

{"omim": ["613845"], "icd-10": ["N15.8"], "synonyms": ["HUPRA syndrome"]}

Rare X-linked dominant genetic disorder Not to be confused with Incontinentia pigmenti achromians. Incontinentia pigmenti Other namesBloch–Siemens syndrome, Bloch–Sulzberger disease, Bloch–Sulzberger syndrome, nelanoblastosis cutis, nevus pigmentosus systematicus[1] This condition is inherited in an X-linked dominant manner. SpecialtyMedical genetics Incontinentia pigmenti (IP) is a rare X-linked dominant genetic disorder that affects the skin, hair, teeth, nails and central nervous system. It is named from its appearance under a microscope.[1] The disease is characterized by skin abnormalities that begin in childhood, usually a blistering rash which heals, followed by the development of harder skin growths. The skin may develop grey or brown patches which fade with time. Other symptoms can include hair loss, dental abnormalities, eye abnormalities that can lead to vision loss and lined or pitted fingernails and toenails. Associated problems can include delayed development, intellectual disability, seizures and other neurological problems. Most males with the disease do not survive to childbirth. Incontinentia pigmenti is caused by a mutation in the IKBKG gene, which encodes the NEMO protein, which serves to protect cells against TNF-alpha-induced apoptosis. A lack of IKBKG therefore makes cells more prone to apoptosis. There is no specific treatment; individual conditions must be managed by specialists.[2] ## Contents * 1 Presentation * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 History * 6 See also * 7 References * 8 External links ## Presentation[edit] Incontinentia pigmenti forming along Blaschko's lines in a 3-year-old girl The skin lesions evolve through characteristic stages: 1. blistering (from birth to about four months of age), 2. a wart-like rash (for several months), 3. swirling macular hyperpigmentation (from about six months of age into adulthood), followed by 4. linear hypopigmentation. Alopecia, dental anomalies, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays or intellectual disability are occasionally seen.[citation needed] The discolored skin is caused by excessive deposits of melanin (normal skin pigment). Most newborns with IP will develop discolored skin within the first two weeks. The pigmentation involves the trunk and extremities, is slate-grey, blue or brown, and is distributed in irregular marbled or wavy lines. The discoloration sometimes fades with age.[citation needed] Neurological problems can include cerebral atrophy, the formation of small cavities in the central white matter of the brain, and the loss of neurons in the cerebellar cortex. About 20% of children with IP will have slow motor development, muscle weakness in one or both sides of the body, intellectual disability, and seizures. They are also likely to have visual problems, which can include: crossed eyes, cataracts, retinal detachment, and severe visual loss. Dental problems are also common, and can include hypodontia, abnormally shaped teeth, and delayed tooth eruption.[3] Breast anomalies can occur in 1% of patients and can include hypoplasia or supernumerary nipples. Skeletal and structural anomalies can occur in approximately 14% of patients, including:[citation needed] * Somatic asymmetry * Hemivertebrae * Scoliosis * Spina bifida * Syndactyly * Acheiria (congenital absence of the hands - note: other limbs may be affected) * Ear anomalies * Extra ribs * Skull deformities ## Genetics[edit] IP is inherited in an X-linked dominant manner.[4][5] IP is lethal in most, but not all, males. A female with IP may have inherited the IKBKG mutation from either parent or have a new gene mutation. Parents may either be clinically affected or have germline mosaicism. Affected women have a 50% risk of transmitting the mutant IKBKG allele at conception; however, most affected male conceptuses miscarry. Thus, the effective ratio for liveborn children from a mother carrying the mutation is 33% unaffected females, 33% affected females, and 33% unaffected males. Genetic counseling, prenatal testing, and preimplantation genetic diagnosis is available.[citation needed] In females, the cells expressing the mutated IKBKG gene due to lyonization selectively die around the time of birth, so the X-inactivation is extremely skewed.[6] IP is caused by mutations in a gene called NEMO (NF-κB essential modulator). ## Diagnosis[edit] The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the NEMO IKBKG gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically. In addition, females with IP have skewed X-chromosome inactivation; testing for this can be used to support the diagnosis. Many people in the past were misdiagnosed with a second type of IP, formerly known as IP1. This has now been given its own name - 'Hypomelanosis of Ito' (incontinentia pigmenti achromians). This has a slightly different presentation: swirls or streaks of hypopigmentation and depigmentation. It is not inherited and does not involve skin stages 1 or 2. Some 33–50% of patients have multisystem involvement — eye, skeletal, and neurological abnormalities. Its chromosomal locus is at Xp11, rather than Xq28. ## Treatment[edit] There does not yet exist a specific treatment for IP. Treatment can only address the individual symptoms.[7] ## History[edit] This disorder was first reported by Swiss dermatologist Bruno Bloch in 1926 and American dermatologist Marion Sulzberger in 1928.[8][9][2] ## See also[edit] * List of cutaneous conditions * List of radiographic findings associated with cutaneous conditions * List of dental abnormalities associated with cutaneous conditions ## References[edit] 1. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.[page needed] 2. ^ a b Sulzberger, Marion B (1928). "Über eine bisher nicht beschriebene congenitale Pigmentanomalie" [About a previously udescribed congenital pigment anomaly]. Archiv für Dermatologie und Syphilis (in German). 154: 19–32. doi:10.1007/bf01828398. S2CID 40446256. 3. ^ Minić, S; Trpinac, D; Gabriel, H; Gencik, M; Obradović, M (January 2013). "Dental and oral anomalies in incontinentia pigmenti: a systematic review". Clin Oral Investig. 17 (1): 1–8. doi:10.1007/s00784-012-0721-5. PMID 22453515. S2CID 73197872. 4. ^ Pettigrew, Rachel; Kuo, Hung-Chih; Scriven, Paul; Rowell, Paula; Pal, Kalyani; Handyside, Alan; Braude, Peter; Ogilvie, Caroline Mackie (2000). "A pregnancy following PGD for X-linked autosomal dominant Incontinentia Pigmenti (Bloch-Sulzberger syndrome): Case Report". Human Reproduction. 15 (12): 2650–2. doi:10.1093/humrep/15.12.2650. PMID 11098039. 5. ^ "Incontinentia pigmenti. DermNet NZ". 6. ^ The International Incontinentia Pigmenti (IP) Consortium; Smahi, Asmae; Courtois, G; Vabres, P; Yamaoka, S; Heuertz, S; Munnich, A; Israël, A; Heiss, Nina S; Klauck, S. M; Kioschis, P; Wiemann, S; Poustka, A; Esposito, Teresa; Bardaro, T; Gianfrancesco, F; Ciccodicola, A; d'Urso, M; Woffendin, Hayley; Jakins, T; Donnai, D; Stewart, H; Kenwrick, S. J; Aradhya, Swaroop; Yamagata, T; Levy, M; Lewis, R. A; Nelson, D. L (2000). "Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti". Nature. 405 (6785): 466–72. Bibcode:2000Natur.405..466T. doi:10.1038/35013114. PMID 10839543. S2CID 186243924. 7. ^ "Incontinentia pigmenti". Medline Plus. Retrieved 26 December 2017. 8. ^ Bloch-Sulzberger pigment dermatosis (Bruno Bloch) at Who Named It? 9. ^ Bloch, B. (1926). "Eigentümliche, bisher nicht beschriebene Pigmentaffektion (incontinentia pigmenti)" [Peculiar, as yet unexplained pigment affection (incontinentia pigmenti)]. Schweizerische medizinische Wochenschrift (in German). Basel. 56: 404–5. ## External links[edit] * GeneReview/NIH/UW entry on Incontinentia Pigmenti Classification D * ICD-10: Q82.3 * ICD-9-CM: 757.33 * OMIM: 308300 * MeSH: D007184 * DiseasesDB: 29600 External resources * MedlinePlus: 001583 * eMedicine: article/1114205 article/1176285 * GeneReviews: Incontinentia pigmenti * Orphanet: 464 * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark * v * t * e Phakomatosis Angiomatosis * Sturge–Weber syndrome * Von Hippel–Lindau disease Hamartoma * Tuberous sclerosis * Hypothalamic hamartoma (Pallister–Hall syndrome) * Multiple hamartoma syndrome * Proteus syndrome * Cowden syndrome * Bannayan–Riley–Ruvalcaba syndrome * Lhermitte–Duclos disease Neurofibromatosis * Type I * Type II Other * Abdallat–Davis–Farrage syndrome * Ataxia telangiectasia * Incontinentia pigmenti * Peutz–Jeghers syndrome * Encephalocraniocutaneous lipomatosis * v * t * e X-linked disorders X-linked recessive Immune * Chronic granulomatous disease (CYBB) * Wiskott–Aldrich syndrome * X-linked severe combined immunodeficiency * X-linked agammaglobulinemia * Hyper-IgM syndrome type 1 * IPEX * X-linked lymphoproliferative disease * Properdin deficiency Hematologic * Haemophilia A * Haemophilia B * X-linked sideroblastic anemia Endocrine * Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy * KAL1 Kallmann syndrome * X-linked adrenal hypoplasia congenita Metabolic * Amino acid: Ornithine transcarbamylase deficiency * Oculocerebrorenal syndrome * Dyslipidemia: Adrenoleukodystrophy * Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency * Pyruvate dehydrogenase deficiency * Danon disease/glycogen storage disease Type IIb * Lipid storage disorder: Fabry's disease * Mucopolysaccharidosis: Hunter syndrome * Purine–pyrimidine metabolism: Lesch–Nyhan syndrome * Mineral: Menkes disease/Occipital horn syndrome Nervous system * X-linked intellectual disability: Coffin–Lowry syndrome * MASA syndrome * Alpha-thalassemia mental retardation syndrome * Siderius X-linked mental retardation syndrome * Eye disorders: Color blindness (red and green, but not blue) * Ocular albinism (1) * Norrie disease * Choroideremia * Other: Charcot–Marie–Tooth disease (CMTX2-3) * Pelizaeus–Merzbacher disease * SMAX2 Skin and related tissue * Dyskeratosis congenita * Hypohidrotic ectodermal dysplasia (EDA) * X-linked ichthyosis * X-linked endothelial corneal dystrophy Neuromuscular * Becker's muscular dystrophy/Duchenne * Centronuclear myopathy (MTM1) * Conradi–Hünermann syndrome * Emery–Dreifuss muscular dystrophy 1 Urologic * Alport syndrome * Dent's disease * X-linked nephrogenic diabetes insipidus Bone/tooth * AMELX Amelogenesis imperfecta No primary system * Barth syndrome * McLeod syndrome * Smith–Fineman–Myers syndrome * Simpson–Golabi–Behmel syndrome * Mohr–Tranebjærg syndrome * Nasodigitoacoustic syndrome X-linked dominant * X-linked hypophosphatemia * Focal dermal hypoplasia * Fragile X syndrome * Aicardi syndrome * Incontinentia pigmenti * Rett syndrome * CHILD syndrome * Lujan–Fryns syndrome * Orofaciodigital syndrome 1 * Craniofrontonasal dysplasia * v * t * e Deficiencies of intracellular signaling peptides and proteins GTP-binding protein regulators GTPase-activating protein * Neurofibromatosis type I * Watson syndrome * Tuberous sclerosis Guanine nucleotide exchange factor * Marinesco–Sjögren syndrome * Aarskog–Scott syndrome * Juvenile primary lateral sclerosis * X-Linked mental retardation 1 G protein Heterotrimeic * cAMP/GNAS1: Pseudopseudohypoparathyroidism * Progressive osseous heteroplasia * Pseudohypoparathyroidism * Albright's hereditary osteodystrophy * McCune–Albright syndrome * CGL 2 Monomeric * RAS: HRAS * Costello syndrome * KRAS * Noonan syndrome 3 * KRAS Cardiofaciocutaneous syndrome * RAB: RAB7 * Charcot–Marie–Tooth disease * RAB23 * Carpenter syndrome * RAB27 * Griscelli syndrome type 2 * RHO: RAC2 * Neutrophil immunodeficiency syndrome * ARF: SAR1B * Chylomicron retention disease * ARL13B * Joubert syndrome 8 * ARL6 * Bardet–Biedl syndrome 3 MAP kinase * Cardiofaciocutaneous syndrome Other kinase/phosphatase Tyrosine kinase * BTK * X-linked agammaglobulinemia * ZAP70 * ZAP70 deficiency Serine/threonine kinase * RPS6KA3 * Coffin-Lowry syndrome * CHEK2 * Li-Fraumeni syndrome 2 * IKBKG * Incontinentia pigmenti * STK11 * Peutz–Jeghers syndrome * DMPK * Myotonic dystrophy 1 * ATR * Seckel syndrome 1 * GRK1 * Oguchi disease 2 * WNK4/WNK1 * Pseudohypoaldosteronism 2 Tyrosine phosphatase * PTEN * Bannayan–Riley–Ruvalcaba syndrome * Lhermitte–Duclos disease * Cowden syndrome * Proteus-like syndrome * MTM1 * X-linked myotubular myopathy * PTPN11 * Noonan syndrome 1 * LEOPARD syndrome * Metachondromatosis Signal transducing adaptor proteins * EDARADD * EDARADD Hypohidrotic ectodermal dysplasia * SH3BP2 * Cherubism * LDB3 * Zaspopathy Other * NF2 * Neurofibromatosis type II * NOTCH3 * CADASIL * PRKAR1A * Carney complex * PRKAG2 * Wolff–Parkinson–White syndrome * PRKCSH * PRKCSH Polycystic liver disease * XIAP * XIAP2 See also intracellular signaling peptides and proteins * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Incontinentia pigmenti

c0021171

wikipedia

https://en.wikipedia.org/wiki/Incontinentia_pigmenti

{"gard": ["6778"], "mesh": ["D007184"], "umls": ["C0021171"], "icd-9": ["757.33"], "orphanet": ["464"], "wikidata": ["Q884590"]}

Hyperprolinemia is an excess of a particular protein building block (amino acid), called proline, in the blood. This condition generally occurs when proline is not broken down properly by the body. There are two inherited forms of hyperprolinemia, called type I and type II. People with hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems. Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This form of the disorder has signs and symptoms that vary in severity, and is more likely than type I to involve seizures or intellectual disability. Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood (lactic acidemia) may have hyperprolinemia as well, because lactic acid inhibits the breakdown of proline. ## Frequency It is difficult to determine the prevalence of hyperprolinemia type I because most people with the condition do not have any symptoms. Hyperprolinemia type II is a rare condition; its prevalence is also unknown. ## Causes Mutations in the ALDH4A1 and PRODH genes cause hyperprolinemia. Inherited hyperprolinemia is caused by deficiencies in the enzymes that break down (degrade) proline. Hyperprolinemia type I is caused by a mutation in the PRODH gene, which provides instructions for producing the enzyme proline oxidase. This enzyme begins the process of degrading proline by starting the reaction that converts it to pyrroline-5-carboxylate. Hyperprolinemia type II is caused by a mutation in the ALDH4A1 gene, which provides instructions for producing the enzyme pyrroline-5-carboxylate dehydrogenase. This enzyme helps to break down the pyrroline-5-carboxylate produced in the previous reaction, converting it to the amino acid glutamate. The conversion between proline and glutamate, and the reverse reaction controlled by different enzymes, are important in maintaining a supply of the amino acids needed for protein production, and for energy transfer within the cell. A deficiency of either proline oxidase or pyrroline-5-carboxylate dehydrogenase results in a buildup of proline in the body. A deficiency of the latter enzyme leads to higher levels of proline and a buildup of the intermediate breakdown product pyrroline-5-carboxylate, causing the signs and symptoms of hyperprolinemia type II. ### Learn more about the genes associated with Hyperprolinemia * ALDH4A1 * PRODH ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. In about one-third of cases, individuals carrying one copy of an altered PRODH gene have moderately elevated levels of proline in their blood, but these levels do not cause any health problems. Individuals with one altered ALDH4A1 gene have normal levels of proline in their blood. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Hyperprolinemia

c0268529

medlineplus

https://medlineplus.gov/genetics/condition/hyperprolinemia/

{"gard": ["6710"], "omim": ["239500", "239510"], "synonyms": []}

Stimmler syndrome is characterised by the association of microcephaly, low birth weight and severe intellectual deficit with dwarfism, small teeth and diabetes mellitus. Two cases have been described. Biochemical tests reveal the presence of high levels of alanine in the urine and elevated alanine, pyruvate and lactate levels in the blood. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Stimmler syndrome

c1859965

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3199

{"gard": ["5026"], "mesh": ["C565968"], "omim": ["202900"]}

Biotin-thiamine-responsive basal ganglia disease is a rare condition that affects the brain and other parts of the nervous system. The severity of the condition and the associated signs and symptoms vary from person to person, even within the same family. Without early diagnosis and treatment, most affected people develop features of the condition between ages 3 and 10 years. Signs and symptoms may include recurrent episodes of confusion, seizures, ataxia (problems coordinating movements), dystonia, facial palsy (weakness of the facial muscles), external ophthalmoplegia (paralysis of the muscles surrounding the eye), and dysphagia. Eventually, these episodes can lead to coma or even death. Biotin-thiamine-responsive basal ganglia disease is caused by changes (mutations) in the SLC19A3 gene and is inherited in an autosomal recessive manner. As its name suggests, early and lifelong treatment with the vitamins biotin and thiamine may improve the symptoms. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Biotin-thiamine-responsive basal ganglia disease

c1843807

gard

https://rarediseases.info.nih.gov/diseases/10237/biotin-thiamine-responsive-basal-ganglia-disease

{"mesh": ["C537658"], "omim": ["607483"], "umls": ["C1843807"], "orphanet": ["65284"], "synonyms": ["Biotin-responsive basal ganglia disease", "BBGD"]}

For the band, see Downy Mildew (band). Downy mildew Example of downy mildew (left) along with powdery mildew on a grape leaf Causal agentsoomycetes Hostsplants Downy mildew refers to any of several types of oomycete microbes that are obligate parasites of plants. Downy mildews exclusively belong to Peronosporaceae. In commercial agriculture, they are a particular problem for growers of crucifers, grapes and vegetables that grow on vines. The prime example is Peronospora farinosa featured in NCBI-Taxonomy[1] and HYP3.[2] This pathogen does not produce survival structures in the northern states of the United States, and overwinters as live mildew colonies in Gulf Coast states. It progresses northward with cucurbit production each spring. Yield loss associated with downy mildew is most likely related to soft rots that occur after plant canopies collapse and sunburn occurs on fruit. Cucurbit downy mildew only affects leaves of cucurbit plants. ## Contents * 1 Symptoms * 2 Treatment and management * 2.1 Cultural options * 2.2 Chemical control * 2.3 Organic control * 3 Plant-specific mildews * 3.1 Basil * 3.2 Cucurbitaceae * 3.3 Grapes * 3.4 Hops * 3.5 Ornamentals * 3.6 Soybeans * 3.7 Spinach * 3.8 Sunflowers * 4 See also * 5 References * 6 External links ## Symptoms[edit] Initial symptoms include large, angular or blocky, yellow areas visible on the upper surface.[3] As lesions mature, they expand rapidly and turn brown. The under surface of infected leaves appears watersoaked. Upon closer inspection, a purple-brown mold (see arrow) becomes apparent. Small spores shaped like footballs can be observed among the mold with a 10x hand lens. In disease-favorable conditions (cool nights with long dew periods), downy mildew will spread rapidly, destroying leaf tissue without affecting stems or petioles.[4] ## Treatment and management[edit] ### Cultural options[edit] Because the downy mildew pathogen does not overwinter in midwestern fields, crop rotations and tillage practices do not affect disease development. The pathogen tends to become established in late summer. Therefore, planting early season varieties may further reduce the already minor threat posed by downy mildew.[4] ### Chemical control[edit] Fungicides applied specifically for downy mildew control may be unnecessary. Broad spectrum protectant fungicides such as chlorothalonil, mancozeb, and fixed copper are at least somewhat effective in protecting against downy mildew infection. Systemic fungicides are labeled for use against cucurbit downy mildew, but are recommended only after diagnosis of this disease has been confirmed.[4] In the United States, the Environmental Protection Agency has approved oxathiapiprolin for use against downy mildew.[5] In Canada, a mixture of zoxamide and mancozeb was registered for control of the mildew under the trademark Gavel (fungicide) as early as 2008.[6] ### Organic control[edit] One way to control downy mildew is to eliminate moisture and humidity around the impacted plants. Watering from below, such as with a drip system, and improve air circulation through selective pruning. In enclosed environments, like in the house or in a greenhouse, reducing the humidity will help as well. ## Plant-specific mildews[edit] ### Basil[edit] Downy mildew of basil caused by Peronospora belbahrii has been a huge problem for both commercial producers and home growers. The disease was first reported in Italy in 2004,[7] was reported in the U.S. in 2007 and 2008[8][9] and has been steadily increasing in prevalence, distribution, and economic importance since then. ### Cucurbitaceae[edit] Cucurbitaceae downy mildew (caused by Pseudoperonospora cubensis) is specific to cucurbits (e.g., cantaloupe (Cucumis melo), cucumber (Cucumis sativus), pumpkin, squash, watermelon (Citrullus lanatus) and other members of the gourd family). The disease is one of the most significant diseases of cucurbits worldwide. ### Grapes[edit] Plasmopara viticola is the causal agent of grapevine downy mildew. ### Hops[edit] Hop Downy Mildew (caused by Pseudoperonospora humuli) is specific to hops (Humulus lupulus). The disease is the single most devastating disease in Western United States hopyards, since the microbe thrives in moist climates. Infected young hop bines become stunted with thickened clusters of pale curled leaves. These spikes have a silvery upper surface, while the undersides of leaves become blackened with spores. These dwarfed spikes are called "basal spikes". 'Lateral' or 'terminal' spikes occur further up the vine. An entire hop crop could be devastated in only a few days. ### Ornamentals[edit] A new and particularly aggressive form of impatiens downy mildew has recently emerged as a major threat to the cultivation of ornamental impatiens in the United States, where they are one of the most popular ornamental plants. ### Soybeans[edit] Peronospora manshurica infects soybeans, reducing photosynthetic activity, yield, and quality.[10] The fungus spreads by oospores on diseased leaves and/or on infected seed. The disease spreads in environments with high humidity and favors temperatures between 20-22 °C. Tufts of grayish to pale-colored sporangiophores on the underside of leaves easily distinguish the infection from other foliar diseases.[11] The disease is often controlled using the fungicides mancozeb, maneb, or zineb.[10] ### Spinach[edit] Downy mildew on spinach is caused by Peronospora effusa, an oomycete pathogen that poses a challenge to spinach production worldwide, especially in organic production. [12] ### Sunflowers[edit] Plasmopara halstedii infects sunflowers, producing oospores which can remain dormant in the soil for many years.[13] ## See also[edit] * Blue mold (of tobacco plants) * Peronosporaceae (with a list of the downy mildew genera) ## References[edit] 1. ^ NCBI-Taxonomy – ncbi.nlm.nih.gov 2. ^ HYP3 – ncbi.nlm.nih.gov 3. ^ Schilder, Annemiek. Downy mildew - Plasmopara viticola. Archived June 11, 2010, at the Wayback Machine MSU Plant Pathology. 4. ^ a b c Richard Latin, Karen Rane, "Pumpkin Diseases" (PDF), Department of Botany and Plant Pathology, purdue.edu 5. ^ "Oxathiapiprolin" (PDF). New Active Ingredient Review. Minnesota Department of Agriculture. October 2015. 6. ^ grainews.ca: "Gowan buys Dow’s Gavel potato fungicide", 18 Jul 2008 7. ^ Garibaldi, A., Minuto, A., Minuto, G., Gullino, M.L., 2004. First Report of Downy Mildew on Basil (Ocimum basilicum) in Italy. Plant Disease 88, 312-312 8. ^ Roberts, P.D., Raid, R.N., Harmon, P.F., Jordan, S.A., Palmateer, A.J., 2009. First Report of Downy Mildew Caused by a Peronospora sp. on Basil in Florida and the United States. Plant Disease 93, 199-199. 9. ^ Wick, R.L., Brazee, N.J., 2009. First Report of Downy Mildew Caused by a Peronospora Species on Sweet Basil (Ocimum basilicum) in Massachusetts. Plant Disease 93, 318-318. 10. ^ a b Shanmugasundaram, S.; Masuda, Ryoichi; Tsou, S.C.S.; Hong, T.L. (1991). Vegetable Soybean Research Needs for Production and Quality Improvement (PDF). Taipei: Asian Vegetable Research and Development Center. pp. 86–87. ISBN 9789290580478. Retrieved 6 February 2016. 11. ^ Sinclair, James Burton; Backman, P. A. (1989). Compendium of Soybean Diseases (3rd ed.). St Paul, MN: APS Press. ISBN 9780890540930. 12. ^ Kandel, Shyam L.; Mou, Beiquan; Shishkoff, Nina; Shi, Ainong; Subbarao, Krishna V.; Klosterman, Steven J. (2019). "Spinach Downy Mildew: Advances in Our Understanding of the Disease Cycle and Prospects for Disease Management". Plant Disease. American Phytopathological Society. 103 (5): 791–803. doi:10.1094/PDIS-10-18-1720-FE. PMID 30939071. 13. ^ Friskop, Andrew; Markell, Sam; Gulya, Tom (2009). "Downy Mildew of Sunflower" (PDF). Sunflower Publications. IPM Publications. Fargo, North Dakota: North Dakota State University Extension Service. Retrieved 4 March 2016. * v * t * e Viticulture Biology and horticulture * Ampelography * Annual growth cycle of grapevines * Grape varieties * Grapes * Hybrid grape * International Grape Genome Program * Ripening (Veraison) * Rootstock * Vineyard * Vitis * Vitis vinifera Environmental variation * Climate categories * Diurnal temperature variation * Drainage * Microclimate * Regional climate levels * Soil types * Terroir * Topography * aspect * elevation * slope Vineyard planting * Grapevine planting * Propagation * Row orientation * Trellis design * Vine training * Yield Vineyard management * Canopy * Clos * Coulure * Erosion control * Fertilizer * Frost damage prevention * Green harvest (Vendange verte) * Integrated pest management * Irrigation * Klopotec * Millerandage * Pruning * Weed control Harvest * Brix * Festivals * Noble rot * Ripeness * Vintage * Weather Pests and diseases * Birds * Black rot * Botrytis bunch rot * Bot canker * Dead arm * Downy mildew * Grapevine yellows * Great French Wine Blight * Lepidoptera * Nematodes * Phylloxera * Pierce's disease * Powdery mildew * Uncinula necator * Red spider mite * Vine moth Approaches and issues * Adaptive management * Biodynamic wine * Effects of climate change on wine production * Environmental stewardship * Organic farming * Sustainable agriculture See also * Glossary of viticulture terms * Glossary of wine terms * Glossary of winemaking terms * Oenology * Outline of wine * Wine * Winemaking ## External links[edit] Authority control * GND: 4314783-5 * NDL: 00569648 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Downy mildew

None

wikipedia

https://en.wikipedia.org/wiki/Downy_mildew

{"wikidata": ["Q1394849"]}

Venous ulcer Other namesVenous insufficiency ulceration, stasis ulcer, stasis dermatitis, varicose ulcer, ulcus cruris, crural ulceration Venous ulcer on the back of the right leg. SpecialtyDermatology Venous ulcers are wounds that are thought to occur due to improper functioning of venous valves, usually of the legs (hence leg ulcers).[1]:846 They are the major occurrence of chronic wounds, occurring in 70% to 90% of leg ulcer cases.[2] Venous ulcers develop mostly along the medial distal leg, and can be painful with negative effects on quality of life.[3] Exercise together with compression stocking increases healing.[4] The NICE guidelines recommends that everyone with a venous leg ulcer, even if healed, should be referred to a "vascular service" for venous duplex ultrasound and assessment for endovenous surgery.[5] ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 3 Diagnosis * 3.1 Classification * 3.2 Distinction from arterial ulcer * 3.3 Differential diagnosis * 4 Prevention * 5 Treatment * 5.1 Compression therapy * 5.2 Medications * 5.3 Skin grafts and artificial skin * 5.4 Surgery * 5.5 Dressings * 6 Prognosis * 7 Research * 8 References * 9 External links ## Signs and symptoms[edit] Signs and symptoms of venous ulcers include: * Moderate pain, which improves on elevation (unlike arterial ulcers which worsen with elevation) * Irregular, sloping edges * Associated oedema, due to increased hydrostatic pressure, which contributes to 'atrophie blanche' * 'Atrophie blanche', localised loss of skin pigmentation due to death of erythrocytes and scarring * Lipodermatosclerosis, a hardening of the skin which can lead to an "inverted champagne bottle" appearance to the leg * Associated superficial varicose veins or "ankle flare", a collection of small, dark, engorged superficial veins[6] * Venous ulcer before surgery * Healing process of a chronic venous stasis ulcer of the lower leg * Healing venous ulcer after one month ## Pathophysiology[edit] The exact cause of venous ulcers is not certain, but a common denominator is generally venous stasis, which may be caused by chronic venous insufficiency,[7] and/or congestive heart failure.[8] Venous stasis causes the pressure in veins to increase.[9][10][11][12] The body needs the pressure gradient between arteries and veins in order for the heart to pump blood forward through arteries and into veins. When venous hypertension exists, arteries no longer have significantly higher pressure than veins, and blood is not pumped as effectively into or out of the area.[9][10][11][12] Venous hypertension may also stretch veins and allow blood proteins to leak into the extravascular space, isolating extracellular matrix (ECM) molecules and growth factors, preventing them from helping to heal the wound.[9][12] Leakage of fibrinogen from veins as well as deficiencies in fibrinolysis may also cause fibrin to build up around the vessels, preventing oxygen and nutrients from reaching cells.[9] Venous insufficiency may also cause white blood cells (leukocytes) to accumulate in small blood vessels, releasing inflammatory factors and reactive oxygen species (ROS, free radicals) and further contributing to chronic wound formation.[9][12] Buildup of white blood cells in small blood vessels may also plug the vessels, further contributing to ischemia.[13] This blockage of blood vessels by leukocytes may be responsible for the "no reflow phenomenon," in which ischemic tissue is never fully reperfused.[13] Allowing blood to flow back into the limb, for example by elevating it, is necessary but also contributes to reperfusion injury.[10] Other comorbidities may also be the root cause of venous ulcers.[11] It is in the crus that the classic venous stasis ulcer occurs. Venous stasis results from damage to the vein valvular system in the lower extremity and in extreme cases allows the pressure in the veins to be higher than the pressure in the arteries. This pressure results in transudation of inflammatory mediators into the subcutaneous tissues of the lower extremity and subsequent breakdown of the tissue including the skin. Wounds of the distal lower extremities arising from causes not directly related to venous insufficiency (e.g., scratch, bite, burn, or surgical incision) may ultimately fail to heal if underlying (often undiagnosed) venous disease is not properly addressed.[citation needed] ## Diagnosis[edit] Venous ulcer (45 x 30 mm). ### Classification[edit] A clinical severity score has been developed to assess chronic venous ulcers. It is based on the CEAP (clinical, etiology, anatomy, and pathophysiology) classification system developed by an expert panel. A high score gives a poor prognosis.[14] ### Distinction from arterial ulcer[edit] A venous ulcer tends to occur on the medial side of the leg, typically around the medial malleolus in the 'gaiter area' whereas arterial ulcer tends to occur on lateral side of the leg and over bony prominences. A venous ulcer is typically shallow with irregular sloping edges whereas an arterial ulcer can be deep and has a 'punched out' appearance. Venous ulcers are typically 'wet' with a moderate to heavy exudate, whereas arterial ulcers are typically 'dry' and scabbed. The skin surrounding a venous ulcer may be edematous (swollen) and there may be evidence of varicose veins; the skin surrounding an arterial ulcer may be pale, cold, shiny and hairless. Both venous and arterial ulcers may be painful, however arterial ulcers tend to be more painful, especially with elevation of the leg, for example when in bed. ### Differential diagnosis[edit] Leg ulcerations may result from various pathologic processes. Common causes of leg ulcerations include inadequate blood flow and oxygen delivery to tissues as seen in peripheral arterial disease and venous stasis ulcerations. Additional causes include neutrophilic skin conditions such as pyoderma gangrenosum or Sweet's syndrome; vasculitic processes such as cryoglobulinemia; calciphylaxis (often seen in people with end-stage kidney disease but may also occur with medications such as warfarin); cancers such as squamous cell carcinoma (Marjolin's ulcer) or myelodysplastic syndrome; neuropathy (e.g., diabetic peripheral neuropathy); or atypical infections such as nocardiosis, sporotrichosis, or mycobacterial infections. ## Prevention[edit] Compression stockings appear to prevent the formation of new ulcers in people with a history of venous ulcers.[15] ## Treatment[edit] The main aim of the treatment is to create such an environment that allows skin to grow across an ulcer. In the majority of cases this requires finding and treating underlying venous reflux. The National Institute for Health and Care Excellence (NICE) recommends referral to a vascular service for anyone with a leg ulcer that has not healed within 2 weeks or anyone with a healed leg ulcer.[16] Most venous ulcers respond to patient education, elevation of foot, elastic compression, and evaluation (known as the Bisgaard regimen).[17] Exercise together with compression stocking increases healing.[4] There is no evidence that antibiotics, whether administered intravenously or by mouth, are useful.[18] Silver products are also not typically useful, while there is some evidence of benefit from cadexomer iodine creams.[18] There is a lack of quality evidence regarding the use of medical grade honey for venous leg ulcers.[19] The recommendations of dressings to treat venous ulcers vary between the countries. Antibiotics are often recommended to be used only if so advised by the physician due to emergence of resistance of bacteria to antibiotics. This is an issue on venous ulcers as they tend to heal slower than acute wounds for example. Natural alternatives that are suitable for the longer term use exists on the market such as honey and resin salve. These products are considered as Medical Devices in EU and the products have to be CE marked.[20][21] There is uncertain evidence whether alginate dressing is effective in the healing of venous ulcer when compared to hydrocolloid dressing or plain non-adherent dressing.[22] It is uncertain whether therapeutic ultrasound improve the healing of venous ulcer.[23] ### Compression therapy[edit] Non-elastic, ambulatory, below knee (BK) compression counters the impact of reflux on venous pump failure. Compression therapy is used for venous leg ulcers and can decrease blood vessel diameter and pressure, which increases their effectiveness, preventing blood from flowing backwards.[9] Compression is also used[9][24] to decrease release of inflammatory cytokines, lower the amount of fluid leaking from capillaries and therefore prevent swelling, and prevent clotting by decreasing activation of thrombin and increasing that of plasmin.[2] Compression is applied using elastic bandages or boots specifically designed for the purpose.[9] Regarding effectiveness, compression dressings improve healing.[25] It is not clear whether non-elastic systems are better than a multilayer elastic system.[25] Patients should wear as much compression as is comfortable.[26] In treatening an existing ulcer, the type of dressing applied beneath the compression does not seem to matter, and hydrocolloid is not better than simple low adherent dressings.[27][28] Good outcomes in ulcer treatment were shown after the application of double compression stockings, e.g. ulcer stockings. These systems contain two different stockings, one often of white colour. This one is to be put on first, is also worn overnight and exerts a basic pressure of 20 mmHg or less. Also it keeps the wound dressing in place. A second stocking, often brown, sometimes black, achieves a pressure of 20–30 mmHg and is applied over the other stocking during the daytime.[29] Intermittent pneumatic compression devices may be used, but it is not clear that they are superior to simple compression dressings.[30] It is not clear if interventions that are aimed to help people adhere to compression therapy are effective.[31] More research is needed in this field. ### Medications[edit] Pentoxifylline is a useful add on treatment to compression stockings and may also help by itself.[32] It works by reducing platelet aggregation and thrombus formation. Gastrointestinal disturbances were reported as a potential adverse effect.[32] Sulodexide, which reduces the formation of blood clots and reduces inflammation, may improve the healing of venous ulcers when taken in conjunction with proper local wound care.[33] Further research is necessary to determine potential adverse effects, the effectiveness, and the dosing protocol for sulodexide treatment. An oral dose of aspirin is being investigated as a potential treatment option for people with venous ulcers. A 2016 Cochrane systematic review concluded that further research is necessary before this treatment option can be confirmed to be safe and effective.[34] Oral zinc supplements have not been proven to be effective in aiding the healing of venous ulcers, however more research is necessary to confirm these results.[35] Treatments aimed at decreasing protease activity to promote healing in chronic wounds have been suggested, however, the benefit remains uncertain.[36] There is also lack of evidence on effectiveness on testing for elevated proteases in venous ulcers and treating them with protease modulating treatment.[37] There is low certainty evidence that protease modulating matrix treatment is helpful in the healing of venous ulcer.[38] Flavonoids may be useful for treating venous ulcers but the evidence needs to be interpreted cautiously.[39] ### Skin grafts and artificial skin[edit] Two layers of skin created from animal sources as a skin graft has been found to be useful in venous leg ulcers.[40] Artificial skin, made of collagen and cultured skin cells, is also used to cover venous ulcers and excrete growth factors to help them heal.[41] A systematic review found that bilayer artificial skin with compression bandaging is useful in the healing of venous ulcers when compared to simple dressings.[40] ### Surgery[edit] A randomized controlled trial found that surgery "reduces the recurrence of ulcers at four years and results in a greater proportion of ulcer free time".[42] Local anaesthetic endovenous surgery using the thermoablation (endovenous laser ablation or radiofrequency), perforator closure (TRLOP) and foam sclerotherapy showed an 85% success rate of healing, with no recurrence of healed ulcers at an average of 3.1 years, and a clinical improvement in 98% in a selected group of venous leg ulcers.[43] No studies are found on the effect of endovenous thermal ablation on ulcer healing, recurrence, and quality of life.[44] The use of subfascial endoscopic perforator surgery is uncertain in the healing of venous ulcer.[45] ### Dressings[edit] It is not certain which dressings and topical agents are most effective for healing venous leg ulcers.[46] Silver-containing dressings may increase the probability of healing for venous leg ulcers.[46] A clinical trial was successfully performed with a mixture of 60% sugar or glucose powder and 40% vaseline.[47] A 2013 Cochrane systematic review aimed to determine the effectiveness of foam dressings for helping to heal venous leg ulcers. The authors concluded that is uncertain whether or not foam dressings are more effective than other dressing types and that more randomized controlled trials are needed to help answer this research question.[48] However, there is some evidence that ibuprofen dressings may offer pain relief to people with venous leg ulcers.[49] ## Prognosis[edit] Venous ulcers are costly to treat, and there is a significant chance that they will recur after healing;[2][9] one study found that up to 48% of venous ulcers had recurred by the fifth year after healing.[9] However treatment with local anaesthetic endovenous techniques suggests a reduction of this high recurrence rate is possible.[43] Without proper care, the ulcer may get infected leading to cellulitis or gangrene and eventually may need amputation of the part of limb in future. Some topical drugs used to treat venous ulcer may cause venous eczema.[50] ## Research[edit] The current 'best' practice in the UK is to treat the underlying venous reflux once an ulcer has healed. It is questionable as to whether endovenous treatment should be offered before ulcer healing, as current evidence would not support this approach as standard care. EVRA (Early Venous Reflux Ablation) ulcer trial – A UK NIHR HTA funded randomised clinical trial to compare early versus delayed endovenous treatment of superficial venous reflux in patients with chronic venous ulceration opened for recruitment in October 2013. The study hopes to show an increase in healing rates from 60% to 75% at 24 weeks.[51] Research from the University of Surrey and funded by the Leg Ulcer Charity looked at the psychological impact of having a leg ulcer, on the relatives and friends of the affected person, and the influence of treatment.[52] ## References[edit] 1. ^ James WD, Berger TG, Elston DM (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. OCLC 968428064. 2. ^ a b c Snyder RJ (2005). "Treatment of nonhealing ulcers with allografts". Clin. Dermatol. 23 (4): 388–95. doi:10.1016/j.clindermatol.2004.07.020. PMID 16023934. 3. ^ Phillips P, Lumley E, Duncan R, Aber A, Woods HB, Jones GL, Michaels J (March 2018). "A systematic review of qualitative research into people's experiences of living with venous leg ulcers" (PDF). Journal of Advanced Nursing. 74 (3): 550–563. doi:10.1111/jan.13465. PMID 28960514. S2CID 206018724. 4. ^ a b Jull A, Slark J, Parsons J (November 2018). "Prescribed Exercise With Compression vs Compression Alone in Treating Patients With Venous Leg Ulcers: A Systematic Review and Meta-analysis". JAMA Dermatology. 154 (11): 1304–1311. doi:10.1001/jamadermatol.2018.3281. PMC 6248128. PMID 30285080. 5. ^ NICE (July 23, 2013). "Varicose veins in the legs: The diagnosis and management of varicose veins. 1.2 Referral to a vascular service". National Institute for Health and Care Excellence. Retrieved June 15, 2019. 6. ^ Farne H, Norris-Cervetto E, Warbrick-Smith J (2015). Oxford cases in medicine and surgery (Second ed.). Oxford. ISBN 978-0198716228. OCLC 923846134. 7. ^ "Chronic Venous Insufficiency (CVI)". Cleveland Clinic. Last reviewed by a Cleveland Clinic medical professional on 05/14/2019. 8. ^ Zhu R, Hu Y, Tang L (2017). "Reduced cardiac function and risk of venous thromboembolism in Asian countries". Thrombosis Journal. 15 (1): 12. doi:10.1186/s12959-017-0135-3. PMC 5404284. PMID 28450810. 9. ^ a b c d e f g h i j Brem H, Kirsner RS, Falanga V (2004). "Protocol for the successful non-surgical treatment of venous ulcers". Am. J. Surg. 188 (1A Suppl): 1–8. doi:10.1016/S0002-9610(03)00284-8. PMID 15223495. 10. ^ a b c Mustoe T (May 2004). "Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy". American Journal of Surgery. 187 (5A): 65S–70S. doi:10.1016/S0002-9610(03)00306-4. PMID 15147994. 11. ^ a b c Moreo K (2005). "Understanding and overcoming the challenges of effective case management for patients with chronic wounds". The Case Manager. 16 (2): 62–3, 67. doi:10.1016/j.casemgr.2005.01.014. PMID 15818347. 12. ^ a b c d Stanley AC, Lounsbury KM, Corrow K, Callas PW, Zhar R, Howe AK, Ricci MA (September 2005). "Pressure elevation slows the fibroblast response to wound healing". Journal of Vascular Surgery. 42 (3): 546–51. doi:10.1016/j.jvs.2005.04.047. PMID 16171604. 13. ^ a b "eMedicine - Reperfusion Injury in Stroke : Article by Wayne M Clark, MD". Retrieved 2007-08-05. 14. ^ Eklöf B, Rutherford RB, Bergan JJ, et al. (2004). "Revision of the CEAP classification for chronic venous disorders: consensus statement". J. Vasc. Surg. 40 (6): 1248–52. doi:10.1016/j.jvs.2004.09.027. PMID 15622385. 15. ^ Nelson EA, Bell-Syer SE (September 2014). "Compression for preventing recurrence of venous ulcers" (PDF). The Cochrane Database of Systematic Reviews. 9 (9): CD002303. doi:10.1002/14651858.CD002303.pub3. PMC 7138196. PMID 25203307. 16. ^ NICE (July 23, 2013). "Varicose veins in the legs: The diagnosis and management of varicose veins. 1.2 Referral to a vascular service". National Institute for Health and Care Excellence. Retrieved August 25, 2014. 17. ^ van Gent WB, Wilschut ED, Wittens C (November 2010). "Management of venous ulcer disease". BMJ. 341: c6045. doi:10.1136/bmj.c6045. PMID 21075818. S2CID 5218584. 18. ^ a b O'Meara S, Al-Kurdi D, Ologun Y, Ovington LG, Martyn-St James M, Richardson R (January 2014). "Antibiotics and antiseptics for venous leg ulcers". The Cochrane Database of Systematic Reviews. 1 (1): CD003557. doi:10.1002/14651858.CD003557.pub5. PMID 24408354. 19. ^ Jull AB, Cullum N, Dumville JC, Westby MJ, Deshpande S, Walker N (March 2015). "Honey as a topical treatment for wounds". The Cochrane Database of Systematic Reviews. 3 (3): CD005083. doi:10.1002/14651858.CD005083.pub4. PMID 25742878. 20. ^ Lohi J, Sipponen A, Jokinen JJ (March 2010). "Local dressings for pressure ulcers: what is the best tool to apply in primary and second care?". Journal of Wound Care. 19 (3): 123–7. doi:10.12968/jowc.2010.19.3.47282. PMID 20559190. 21. ^ "Regulation (Eu) 2017/745 of the European Parliament and of the Council on medical devices". Official Journal of the European Union. 5 April 2017. 22. ^ O'Meara S, Martyn-St James M, Adderley UJ, et al. (Cochrane Wounds Group) (August 2015). "Alginate dressings for venous leg ulcers". The Cochrane Database of Systematic Reviews (8): CD010182. doi:10.1002/14651858.CD010182.pub3. PMC 7087437. PMID 26286189. 23. ^ Cullum, Nicky; Liu, Zhenmi (2017-05-15). Cochrane Wounds Group (ed.). "Therapeutic ultrasound for venous leg ulcers". Cochrane Database of Systematic Reviews. 2017 (5): CD001180. doi:10.1002/14651858.CD001180.pub4. PMC 6481488. PMID 28504325. 24. ^ Taylor JE, Laity PR, Hicks J, et al. (2005). "Extent of iron pick-up in deforoxamine-coupled polyurethane materials for therapy of chronic wounds". Biomaterials. 26 (30): 6024–33. doi:10.1016/j.biomaterials.2005.03.015. PMID 15885771. 25. ^ a b Nelson EA, Cullum N, Jones J (2006). "Venous leg ulcers". Clin Evid (15): 2607–26. PMID 16973096. 26. ^ Nelson EA, Harper DR, Prescott RJ, Gibson B, Brown D, Ruckley CV (2006). "Prevention of recurrence of venous ulceration: randomized controlled trial of class 2 and class 3 elastic compression". J. Vasc. Surg. 44 (4): 803–8. doi:10.1016/j.jvs.2006.05.051. PMID 17012004. 27. ^ Palfreyman SJ, Nelson EA, Lochiel R, Michaels JA (July 2006). Palfreyman SS (ed.). "Dressings for healing venous leg ulcers". The Cochrane Database of Systematic Reviews (3): CD001103. doi:10.1002/14651858.CD001103.pub2. PMID 16855958. (Retracted, see doi:10.1002/14651858.cd001103.pub3. If this is an intentional citation to a retracted paper, please replace `{{Retracted}}` with `{{Retracted|intentional=yes}}`.) 28. ^ Palfreyman S, Nelson EA, Michaels JA (2007). "Dressings for venous leg ulcers: systematic review and meta-analysis". BMJ. 335 (7613): 244. doi:10.1136/bmj.39248.634977.AE. PMC 1939774. PMID 17631512. 29. ^ Partsch H, Mortimer P (2015). "Compression for leg wounds". Br. J. Dermatol. 173 (2): 359–69. doi:10.1111/bjd.13851. PMID 26094638. 30. ^ Nelson EA, Hillman A, Thomas K (2014). "Intermittent pneumatic compression for treating venous leg ulcers". Cochrane Database Syst Rev. 5 (5): CD001899. arXiv:quant-ph/0403227. doi:10.1002/14651858.CD001899.pub4. PMID 24820100. 31. ^ Weller CD, Buchbinder R, Johnston RV (March 2016). "Interventions for helping people adhere to compression treatments for venous leg ulceration". The Cochrane Database of Systematic Reviews. 3: CD008378. doi:10.1002/14651858.CD008378.pub3. PMC 6823259. PMID 26932818. 32. ^ a b Jull AB, Arroll B, Parag V, Waters J (December 2012). "Pentoxifylline for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 12: CD001733. doi:10.1002/14651858.CD001733.pub3. PMC 7061323. PMID 23235582. 33. ^ Wu B, Lu J, Yang M, Xu T (June 2016). "Sulodexide for treating venous leg ulcers". The Cochrane Database of Systematic Reviews (6): CD010694. doi:10.1002/14651858.CD010694.pub2. PMID 27251175. 34. ^ de Oliveira Carvalho PE, Magolbo NG, De Aquino RF, Weller CD (February 2016). "Oral aspirin for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 2: CD009432. doi:10.1002/14651858.CD009432.pub2. PMID 26889740. 35. ^ Wilkinson EA (September 2014). "Oral zinc for arterial and venous leg ulcers". The Cochrane Database of Systematic Reviews (9): CD001273. doi:10.1002/14651858.CD001273.pub3. PMC 6486207. PMID 25202988. 36. ^ Westby MJ, Dumville JC, Stubbs N, Norman G, Wong JK, Cullum N, Riley RD (September 2018). "Protease activity as a prognostic factor for wound healing in venous leg ulcers". The Cochrane Database of Systematic Reviews. 9 (9): CD012841. doi:10.1002/14651858.CD012841.pub2. PMC 6513613. PMID 30171767. 37. ^ Norman G, Westby MJ, Stubbs N, Dumville JC, Cullum N, et al. (Cochrane Wounds Group) (January 2016). "A 'test and treat' strategy for elevated wound protease activity for healing in venous leg ulcers". The Cochrane Database of Systematic Reviews (1): CD011753. doi:10.1002/14651858.CD011753.pub2. PMID 26771894. 38. ^ Westby MJ, Norman G, Dumville JC, Stubbs N, Cullum N, et al. (Cochrane Wounds Group) (December 2016). "Protease-modulating matrix treatments for healing venous leg ulcers". The Cochrane Database of Systematic Reviews. 12: CD011918. doi:10.1002/14651858.CD011918.pub2. PMC 6463954. PMID 27977053. 39. ^ Scallon C, Bell-Syer SE, Aziz Z, et al. (Cochrane Wounds Group) (May 2013). "Flavonoids for treating venous leg ulcers". The Cochrane Database of Systematic Reviews (5): CD006477. doi:10.1002/14651858.CD006477.pub2. PMID 23728661. 40. ^ a b Jones JE, Nelson EA, Al-Hity A (January 2013). "Skin grafting for venous leg ulcers". The Cochrane Database of Systematic Reviews. 1 (1): CD001737. doi:10.1002/14651858.CD001737.pub4. PMC 7061325. PMID 23440784. 41. ^ Mustoe T (March 17–18, 2005). Dermal ulcer healing: Advances in understanding. Tissue repair and ulcer/wound healing: molecular mechanisms, therapeutic targets and future directions. Paris, France. 42. ^ Gohel MS, Barwell JR, Taylor M, et al. (July 2007). "Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial". BMJ. 335 (7610): 83. doi:10.1136/bmj.39216.542442.BE. PMC 1914523. PMID 17545185. 43. ^ a b Thomas CA, Holdstock JM, Harrison CC, Price BA, Whiteley MS (April 2013). "Healing rates following venous surgery for chronic venous leg ulcers in an independent specialist vein unit". Phlebology. 28 (3): 132–9. doi:10.1258/phleb.2012.011097. PMID 22833505. S2CID 9186619. 44. ^ Samuel N, Carradice D, Wallace T, Smith GE, Chetter IC, et al. (Cochrane Wounds Group) (October 2013). "Endovenous thermal ablation for healing venous ulcers and preventing recurrence". The Cochrane Database of Systematic Reviews (10): CD009494. doi:10.1002/14651858.CD009494.pub2. PMC 6492493. PMID 24096603. 45. ^ Lin ZC, Loveland PM, Johnston RV, Bruce M, Weller CD, et al. (Cochrane Wounds Group) (March 2019). "Subfascial endoscopic perforator surgery (SEPS) for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 3: CD012164. doi:10.1002/14651858.CD012164.pub2. PMC 6397791. PMID 30827037. 46. ^ a b Norman G, Westby MJ, Rithalia AD, Stubbs N, Soares MO, Dumville JC (June 2018). "Dressings and topical agents for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 6: CD012583. doi:10.1002/14651858.CD012583.pub2. PMC 6513558. PMID 29906322. 47. ^ Anti-Infective Effects of Sugar-Vaseline Mixture on Leg Ulcers 48. ^ O'Meara S, Martyn-St James M (May 2013). "Foam dressings for venous leg ulcers". The Cochrane Database of Systematic Reviews (5): CD009907. doi:10.1002/14651858.cd009907.pub2. PMID 23728697. 49. ^ Briggs M, Nelson EA, Martyn-St James M, et al. (Cochrane Wounds Group) (November 2012). "Topical agents or dressings for pain in venous leg ulcers". The Cochrane Database of Systematic Reviews. 11: CD001177. doi:10.1002/14651858.CD001177.pub3. PMC 7054838. PMID 23152206. 50. ^ Marks R (2003-04-30). Roxburgh's Common Skin Diseases (17th ed.). p. 127. ISBN 978-0-340-76232-5. 51. ^ Davies A, Heatley F. "EVRA (Early Venous Reflux Ablation) Ulcer Trial". Faculty of Medicine Imperial College London. 52. ^ Tollow P (April 2014). "Impact of Leg Ulcers on Relatives and Carers of Affected Patients - A PhD Study funded by The Leg Ulcer Charity". The Leg Ulcer Charity. Retrieved August 25, 2014. ## External links[edit] Classification D * ICD-10: I83.0, I83.2, L97 * ICD-9-CM: 454.0 * MeSH: D014647 * DiseasesDB: 29114 External resources * MedlinePlus: 000834 * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Venous ulcer

c0042344

wikipedia

https://en.wikipedia.org/wiki/Venous_ulcer

{"mesh": ["D014647"], "icd-9": ["454.0"], "icd-10": ["I83.2", "I83.0"], "wikidata": ["Q1573613"]}

Pneumococcal infection Other namesPneumococcosis SpecialtyRespirology, neurology A pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae, which is also called the pneumococcus. S. pneumoniae is a common member of the bacterial flora colonizing the nose and throat of 5–10% of healthy adults and 20–40% of healthy children.[1] However, it is also a cause of significant disease, being a leading cause of pneumonia, bacterial meningitis, and sepsis. The World Health Organization estimates that in 2005 pneumococcal infections were responsible for the death of 1.6 million children worldwide.[2] ## Contents * 1 Infections * 2 Pathogenesis * 2.1 Virulence factors * 3 Diagnosis * 4 Prevention * 5 Treatment * 6 History * 7 References * 8 External links ## Infections[edit] Pneumococcal meningitis Pneumococcal pneumonia represents 15%–50% of all episodes of community-acquired pneumonia, 30–50% of all cases of acute otitis media, and a significant proportion of bloodstream infections and bacterial meningitis.[3] As estimated by WHO in 2005 it killed about 1.6 million children every year worldwide with 0.7–1 million of them being under the age of five. The majority of these deaths were in developing countries.[2] ## Pathogenesis[edit] S. pneumoniae is normally found in the nose and throat of 5–10% of healthy adults and 20–40% of healthy children.[1] It can be found in higher amounts in certain environments, especially those where people are spending a great deal of time in close proximity to each other (day-care centers, military barracks). It attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. This normal colonization can become infectious if the organisms are carried into areas such as the Eustachian tube or nasal sinuses where it can cause otitis media and sinusitis, respectively. Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, or smoking-induced ciliary paralysis might be contributing factors). The organism's polysaccharide capsule makes it resistant to phagocytosis and if there is no pre-existing anticapsular antibody alveolar macrophages cannot adequately kill the pneumococci. The organism spreads to the blood stream (where it can cause bacteremia) and is carried to the meninges, joint spaces, bones, and peritoneal cavity, and may result in meningitis, brain abscess, septic arthritis, or osteomyelitis. S. pneumoniae has several virulence factors, including the polysaccharide capsule mentioned earlier, that help it evade a host's immune system. It has pneumococcal surface proteins that inhibit complement-mediated opsonization, and it secretes IgA1 protease that will destroy secretory IgA produced by the body and mediates its attachment to respiratory mucosa. The risk of pneumococcal infection is much increased in persons with impaired IgG synthesis, impaired phagocytosis, or defective clearance of pneumococci. In particular, the absence of a functional spleen, through congenital asplenia, surgical removal of the spleen, or sickle-cell disease predisposes one to a more severe course of infection (overwhelming post-splenectomy infection) and prevention measures are indicated (see asplenia). People with a compromised immune system, such as those living with HIV, are also at higher risk of pneumococcal disease.[4] In HIV patients with access to treatment, the risk of invasive pneumoccal disease is 0.2–1% per year and has a fatality rate of 8%.[4] There is an association between pneumococcal pneumonia and influenza.[5] Damage to the lining of the airways (respiratory epithelium) and upper respiratory system caused by influenza may facilitate pneumococcal entry and infection. Other risk factors include smoking, injection drug use, Hepatitis C, and COPD.[4] ### Virulence factors[edit] S. pneumoniae expresses different virulence factors on its cell surface and inside the organism. These virulence factors contribute to some of the clinical manifestations during infection with S. pneumoniae. * Polysaccharide capsule—prevents phagocytosis by host immune cells by inhibiting C3b opsonization of the bacterial cells * Pneumolysin (Ply)—a 53-kDa pore-forming protein that can cause lysis of host cells and activate complement * Autolysin (LytA)—activation of this protein lyses the bacteria releasing its internal contents (i.e., pneumolysin) * Hydrogen peroxide—causes damage to host cells (can cause apoptosis in neuronal cells during meningitis) and has bactericidal effects against competing bacteria (Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus)[6][7] * Pili—hair-like structures that extend from the surface of many strains of S. pneumoniae. They contribute to colonization of upper respiratory tract and increase the formation of large amounts of TNF by the immune system during sepsis, raising the possibility of septic shock[8] * Choline binding protein A/Pneumococcal surface protein A (CbpA/PspA)—an adhesin that can interact with carbohydrates on the cell surface of pulmonary epithelial cells and can inhibit complement-mediated opsonization of pneumococci * Competence for genetic transformation likely plays an important role in nasal colonization fitness and virulence (lung infectivity)[9] ## Diagnosis[edit] Depending on the nature of infection an appropriate sample is collected for laboratory identification. Pneumococci are typically gram-positive cocci seen in pairs or chains. When cultured on blood agar plates with added optochin antibiotic disk they show alpha-hemolytic colonies and a clear zone of inhibition around the disk indicating sensitivity to the antibiotic. Pneumococci are also bile soluble. Just like other streptococci they are catalase-negative. A Quellung test can identify specific capsular polysaccharides.[10] Pneumococcal antigen (cell wall C polysaccharide) may be detected in various body fluids. Older detection kits, based on latex agglutination, added little value above Gram staining and were occasionally false-positive. Better results are achieved with rapid immunochromatography, which has a sensitivity (identifies the cause) of 70–80% and >90% specificity (when positive identifies the actual cause) in pneumococcal infections. The test was initially validated on urine samples but has been applied successfully to other body fluids.[10] Chest X-rays can also be conducted to confirm inflammation though are not specific to the causative agent. ## Prevention[edit] Main article: Pneumococcal vaccine Due to the importance of disease caused by S. pneumoniae several vaccines have been developed to protect against invasive infection. The World Health Organization recommend routine childhood pneumococcal vaccination;[11] it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom,[12] United States,[13] and South Africa.[14] ## Treatment[edit] Throughout history treatment relied primarily on β-lactam antibiotics. In the 1960s nearly all strains of S. pneumoniae were susceptible to penicillin, but more recently there has been an increasing prevalence of penicillin resistance especially in areas of high antibiotic use. A varying proportion of strains may also be resistant to cephalosporins, macrolides (such as erythromycin), tetracycline, clindamycin and the fluoroquinolones. Penicillin-resistant strains are more likely to be resistant to other antibiotics. Most isolates remain susceptible to vancomycin, though its use in a β-lactam-susceptible isolate is less desirable because of tissue distribution of the medication and concerns of development of vancomycin resistance. More advanced beta-lactam antibiotics (cephalosporins) are commonly used in combination with other antibiotics to treat meningitis and community-acquired pneumonia. In adults recently developed fluoroquinolones such as levofloxacin and moxifloxacin are often used to provide empiric coverage for patients with pneumonia, but in parts of the world where these medications are used to treat tuberculosis, resistance has been described.[15] Susceptibility testing should be routine with empiric antibiotic treatment guided by resistance patterns in the community in which the organism was acquired. There is currently debate as to how relevant the results of susceptibility testing are to clinical outcome.[16][17] There is slight clinical evidence that penicillins may act synergistically with macrolides to improve outcomes.[18] Resistant Pneumococci strains are called penicillin-resistant Pneumococci (PRP),[19] penicillin-resistant Streptococcus pneumoniae (PRSP),[20] Streptococcus pneumoniae penicillin resistant (SPPR),[21] or drug-resistant Strepotococcus pneumomoniae (DRSP).[22] ## History[edit] In the 19th century it was demonstrated that immunization of rabbits with killed pneumococci protected them against subsequent challenge with viable pneumococci. Serum from immunized rabbits or from humans who had recovered from pneumococcal pneumonia also conferred protection. In the 20th century, the efficacy of immunization was demonstrated in South African miners. It was discovered that the pneumococcus's capsule made it resistant to phagocytosis, and in the 1920s it was shown that an antibody specific for capsular polysaccharide aided the killing of S. pneumoniae. In 1936, a pneumococcal capsular polysaccharide vaccine was used to abort an epidemic of pneumococcal pneumonia. In the 1940s, experiments on capsular transformation by pneumococci first identified DNA as the material that carries genetic information.[23] In 1900 it was recognized that different serovars of pneumococci exist and that immunization with a given serovar did not protect against infection with other serovars. Since then over ninety serovars have been discovered each with a unique polysaccharide capsule that can be identified by the quellung reaction. Because some of these serovars cause disease more commonly than others it is possible to provide reasonable protection by immunizing with less than 90 serovars; current vaccines contain up to 23 serovars (i.e., it is "23-valent"). The serovars are numbered according to two systems: the American system, which numbers them in the order in which they were discovered, and the Danish system, which groups them according to antigenic similarities. ## References[edit] 1. ^ a b Ryan KJ; Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9. 2. ^ a b WHO (2007). "Pneumococcal conjugate vaccine for childhood immunization—WHO position paper" (PDF). Wkly Epidemiol Rec. Geneva: World Health Organization. 82 (12): 93–104. PMID 17380597. 3. ^ Verma R, Khanna P (2012) Pneumococcal conjugate vaccine: A newer vaccine available in India. Hum Vaccin Immunother 8(9) 4. ^ a b c Siemieniuk, Reed A.C.; Gregson, Dan B.; Gill, M. John (Nov 2011). "The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study". BMC Infectious Diseases. 11 (314): 314. doi:10.1186/1471-2334-11-314. PMC 3226630. PMID 22078162. 5. ^ Walter ND, Taylor TH, Shay DK, et al. (2010). "Influenza Circulation and the Burden of Invasive Pneumococcal Pneumonia during a Non‐pandemic Period in the United States". Clin Infect Dis. 50 (2): 175–183. doi:10.1086/649208. PMID 20014948. 6. ^ Pericone, Christopher D.; Overweg, Karin; Hermans, Peter W. M.; Weiser, Jeffrey N. (2000). "Inhibitory and Bactericidal Effects of Hydrogen Peroxide Production by Streptococcus pneumoniae on Other Inhabitants of the Upper Respiratory Tract". Infect Immun. 68 (7): 3990–3997. doi:10.1128/IAI.68.7.3990-3997.2000. PMC 101678. PMID 10858213. 7. ^ Regev-Yochay G, Trzcinski K, Thompson CM, Malley R, Lipsitch M (2006). "Interference between Streptococcus pneumoniae and Staphylococcus aureus: In vitro hydrogen peroxide-mediated killing by Streptococcus pneumoniae". J Bacteriol. 188 (13): 4996–5001. doi:10.1128/JB.00317-06. PMC 1482988. PMID 16788209. 8. ^ Barocchi M, Ries J, Zogaj X, Hemsley C, Albiger B, Kanth A, Dahlberg S, Fernebro J, Moschioni M, Masignani V, Hultenby K, Taddei A, Beiter K, Wartha F, von Euler A, Covacci A, Holden D, Normark S, Rappuoli R, Henriques-Normark B (2006). "A pneumococcal pilus influences virulence and host inflammatory responses". Proc Natl Acad Sci USA. 103 (8): 2857–2862. doi:10.1073/pnas.0511017103. PMC 1368962. PMID 16481624. 9. ^ Li G, Liang Z, Wang X, Yang Y, Shao Z, Li M, Ma Y, Qu F, Morrison DA, Zhang JR (2016). "Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence". Infect. Immun. 84 (6): 1887–901. doi:10.1128/IAI.00097-16. PMC 4907133. PMID 27068094. 10. ^ a b Werno AM, Murdoch DR (March 2008). "Medical microbiology: laboratory diagnosis of invasive pneumococcal disease". Clin. Infect. Dis. 46 (6): 926–32. doi:10.1086/528798. PMID 18260752. 11. ^ "Pneumococcal vaccines WHO position paper—2012" (PDF). Wkly Epidemiol Rec. 87 (14): 129–44. Apr 6, 2012. PMID 24340399. 12. ^ "Children to be given new vaccine". BBC News. 8 February 2006. 13. ^ "Pneumococcal Vaccination: Information for Health Care Providers". cdc.org. Retrieved 26 July 2016. 14. ^ "Critical decline in pneumococcal disease and antibiotic resistance in South Africa". NICD. Retrieved 20 July 2015. 15. ^ Group For Enteric; Von Gottberg, A.; Klugman, K. P.; Cohen, C.; Wolter, N.; De Gouveia, L.; Du Plessis, M.; Mpembe, R.; Quan, V.; Whitelaw, A.; Hoffmann, R.; Govender, N.; Meiring, S.; Smith, A. M.; Schrag, S. (2008). "Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study". The Lancet. 371 (9618): 1108–1113. doi:10.1016/S0140-6736(08)60350-5. PMID 18359074. 16. ^ Peterson LR (2006). "Penicillins for treatment of pneumococcal pneumonia: does in vitro resistance really matter?". Clin Infect Dis. 42 (2): 224–33. doi:10.1086/497594. PMID 16355333. 17. ^ Tleyjeh IM, Tlaygeh HM, Hejal R, Montori VM, Baddour LM (2006). "The impact of penicillin resistance on short-term mortality in hospitalized adults with pneumococcal pneumonia: a systematic review and meta-analysis". Clin Infect Dis. 42 (6): 788–97. doi:10.1086/500140. PMID 16477555. 18. ^ Martínez JA, Horcajada JP, Almela M, et al. (2003). "Addition of a Macrolide to a β-Lactam based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia". Clin Infect Dis. 36 (4): 389–395. doi:10.1086/367541. PMID 12567294. 19. ^ Nilsson, P; Laurell, MH (2001). "Carriage of penicillin-resistant Streptococcus pneumoniae by children in day-care centers during an intervention program in Malmo, Sweden". The Pediatric Infectious Disease Journal. 20 (12): 1144–9. doi:10.1097/00006454-200112000-00010. PMID 11740321. 20. ^ Block, SL; Harrison, CJ; Hedrick, JA; Tyler, RD; Smith, RA; Keegan, E; Chartrand, SA (1995). "Penicillin-resistant Streptococcus pneumoniae in acute otitis media: risk factors, susceptibility patterns and antimicrobial management". The Pediatric Infectious Disease Journal. 14 (9): 751–9. doi:10.1097/00006454-199509000-00005. PMID 8559623. 21. ^ Koiuszko, S; Bialucha, A; Gospodarek, E (2007). "[The drug susceptibility of penicillin-resistant Streptococcus pneumoniae]". Medycyna Doswiadczalna I Mikrobiologia. 59 (4): 293–300. PMID 18416121. 22. ^ "Drug Resistance". cdc.gov. 2019-02-13. Retrieved 17 February 2019. 23. ^ Avery OT, Macleod CM, McCarty M (1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types". J. Exp. Med. 79 (2): 137–58. doi:10.1084/jem.79.2.137. PMC 2135445. PMID 19871359. ## External links[edit] Classification D * MeSH: D011008 * November 2nd: World Pneumonia Day Website * Pneumococcal Vaccine Accelerated Development and Introduction Plan * v * t * e * Firmicutes (low-G+C) Infectious diseases * Bacterial diseases: G+ Bacilli Lactobacillales (Cat-) Streptococcus α optochin susceptible * S. pneumoniae * Pneumococcal infection optochin resistant * Viridans streptococci: S. mitis * S. mutans * S. oralis * S. sanguinis * S. sobrinus * S. anginosus group β A * bacitracin susceptible: S. pyogenes * Group A streptococcal infection * Streptococcal pharyngitis * Scarlet fever * Erysipelas * Rheumatic fever B * bacitracin resistant, CAMP test+: S. agalactiae * Group B streptococcal infection ungrouped * Streptococcus iniae * Cutaneous Streptococcus iniae infection γ * D * BEA+: Streptococcus bovis Enterococcus * BEA+: Enterococcus faecalis * Urinary tract infection * Enterococcus faecium Bacillales (Cat+) Staphylococcus Cg+ * S. aureus * Staphylococcal scalded skin syndrome * Toxic shock syndrome * MRSA Cg- * novobiocin susceptible * S. epidermidis * novobiocin resistant * S. saprophyticus Bacillus * Bacillus anthracis * Anthrax * Bacillus cereus * Food poisoning Listeria * Listeria monocytogenes * Listeriosis Clostridia Clostridium (spore-forming) motile: * Clostridium difficile * Pseudomembranous colitis * Clostridium botulinum * Botulism * Clostridium tetani * Tetanus nonmotile: * Clostridium perfringens * Gas gangrene * Clostridial necrotizing enteritis Finegoldia (non-spore forming) * Finegoldia magna Mollicutes Mycoplasmataceae * Ureaplasma urealyticum * Ureaplasma infection * Mycoplasma genitalium * Mycoplasma pneumoniae * Mycoplasma pneumonia Anaeroplasmatales * Erysipelothrix rhusiopathiae * Erysipeloid * v * t * e Meningitis and other diseases of meninges Meningitis * Arachnoiditis * Bacterial * Tuberculous * Haemophilus * Pneumococcal * Viral * Herpesviral * Fungal * Cryptococcal * Aseptic * Drug-induced Other * Meningoencephalitis * v * t * e Diseases of the respiratory system Upper RT (including URTIs, common cold) Head sinuses Sinusitis nose Rhinitis Vasomotor rhinitis Atrophic rhinitis Hay fever Nasal polyp Rhinorrhea nasal septum Nasal septum deviation Nasal septum perforation Nasal septal hematoma tonsil Tonsillitis Adenoid hypertrophy Peritonsillar abscess Neck pharynx Pharyngitis Strep throat Laryngopharyngeal reflux (LPR) Retropharyngeal abscess larynx Croup Laryngomalacia Laryngeal cyst Laryngitis Laryngopharyngeal reflux (LPR) Laryngospasm vocal cords Laryngopharyngeal reflux (LPR) Vocal fold nodule Vocal fold paresis Vocal cord dysfunction epiglottis Epiglottitis trachea Tracheitis Laryngotracheal stenosis Lower RT/lung disease (including LRTIs) Bronchial/ obstructive acute Acute bronchitis chronic COPD Chronic bronchitis Acute exacerbation of COPD) Asthma (Status asthmaticus Aspirin-induced Exercise-induced Bronchiectasis Cystic fibrosis unspecified Bronchitis Bronchiolitis Bronchiolitis obliterans Diffuse panbronchiolitis Interstitial/ restrictive (fibrosis) External agents/ occupational lung disease Pneumoconiosis Aluminosis Asbestosis Baritosis Bauxite fibrosis Berylliosis Caplan's syndrome Chalicosis Coalworker's pneumoconiosis Siderosis Silicosis Talcosis Byssinosis Hypersensitivity pneumonitis Bagassosis Bird fancier's lung Farmer's lung Lycoperdonosis Other * ARDS * Combined pulmonary fibrosis and emphysema * Pulmonary edema * Löffler's syndrome/Eosinophilic pneumonia * Respiratory hypersensitivity * Allergic bronchopulmonary aspergillosis * Hamman-Rich syndrome * Idiopathic pulmonary fibrosis * Sarcoidosis * Vaping-associated pulmonary injury Obstructive / Restrictive Pneumonia/ pneumonitis By pathogen * Viral * Bacterial * Pneumococcal * Klebsiella * Atypical bacterial * Mycoplasma * Legionnaires' disease * Chlamydiae * Fungal * Pneumocystis * Parasitic * noninfectious * Chemical/Mendelson's syndrome * Aspiration/Lipid By vector/route * Community-acquired * Healthcare-associated * Hospital-acquired By distribution * Broncho- * Lobar IIP * UIP * DIP * BOOP-COP * NSIP * RB Other * Atelectasis * circulatory * Pulmonary hypertension * Pulmonary embolism * Lung abscess Pleural cavity/ mediastinum Pleural disease * Pleuritis/pleurisy * Pneumothorax/Hemopneumothorax Pleural effusion Hemothorax Hydrothorax Chylothorax Empyema/pyothorax Malignant Fibrothorax Mediastinal disease * Mediastinitis * Mediastinal emphysema Other/general * Respiratory failure * Influenza * Common cold * SARS * Coronavirus disease 2019 * Idiopathic pulmonary haemosiderosis * Pulmonary alveolar proteinosis *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Pneumococcal infection

c0032269

wikipedia

https://en.wikipedia.org/wiki/Pneumococcal_infection

{"mesh": ["D011008"], "wikidata": ["Q4366062"]}

Langerhans cell histiocytosis is a disorder in which excess immune system cells called Langerhans cells build up in the body. Langerhans cells, which help regulate the immune system, are normally found throughout the body, especially in the skin, lymph nodes, spleen, lungs, liver, and bone marrow. In Langerhans cell histiocytosis, excess immature Langerhans cells usually form tumors called granulomas. Many researchers now consider Langerhans cell histiocytosis to be a form of cancer, but this classification remains controversial. In approximately 80 percent of affected individuals, one or more granulomas develop in the bones, causing pain and swelling. The granulomas, which usually occur in the skull or the long bones of the arms or legs, may cause the bone to fracture. Granulomas also frequently occur in the skin, appearing as blisters, reddish bumps, or rashes which can be mild to severe. The pituitary gland may also be affected; this gland is located at the base of the brain and produces hormones that control many important body functions. Without hormone supplementation, affected individuals may experience delayed or absent puberty or an inability to have children (infertility). In addition, pituitary gland damage may result in the production of excessive amounts of urine (diabetes insipidus) and dysfunction of another gland called the thyroid. Thyroid dysfunction can affect the rate of chemical reactions in the body (metabolism), body temperature, skin and hair texture, and behavior. In 15 to 20 percent of cases, Langerhans cell histiocytosis affects the lungs, liver, or blood-forming (hematopoietic) system; damage to these organs and tissues may be life-threatening. Lung involvement, which appears as swelling of the small airways (bronchioles) and blood vessels of the lungs, results in stiffening of the lung tissue, breathing problems, and increased risk of infection. Hematopoietic involvement, which occurs when the Langerhans cells crowd out blood-forming cells in the bone marrow, leads to a general reduction in the number of blood cells (pancytopenia). Pancytopenia results in fatigue due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia). Other signs and symptoms that may occur in Langerhans cell histiocytosis, depending on which organs and tissues have Langerhans cell deposits, include swollen lymph nodes, abdominal pain, yellowing of the skin and whites of the eyes (jaundice), delayed puberty, protruding eyes, dizziness, irritability, and seizures. About 1 in 50 affected individuals experience deterioration of neurological function (neurodegeneration). Langerhans cell histiocytosis is often diagnosed in childhood, usually between ages 2 and 3, but can appear at any age. Most individuals with adult-onset Langerhans cell histiocytosis are current or past smokers; in about two-thirds of adult-onset cases the disorder affects only the lungs. The severity of Langerhans cell histiocytosis, and its signs and symptoms, vary widely among affected individuals. Certain presentations or forms of the disorder were formerly considered to be separate diseases. Older names that were sometimes used for forms of Langerhans cell histiocytosis include eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease. In many people with Langerhans cell histiocytosis, the disorder eventually goes away with appropriate treatment. It may even disappear on its own, especially if the disease occurs only in the skin. However, some complications of the condition, such as diabetes insipidus or other effects of tissue and organ damage, may be permanent. ## Frequency Langerhans cell histiocytosis is a rare disorder. Its prevalence is estimated at 1 to 2 in 100,000 people. ## Causes Somatic mutations in the BRAF gene have been identified in the Langerhans cells of about half of individuals with Langerhans cell histiocytosis. Somatic gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are not inherited. The BRAF gene provides instructions for making a protein that is normally switched on and off in response to signals that control cell growth and development. Somatic mutations cause the BRAF protein in affected cells to be continuously active and to transmit messages to the nucleus even in the absence of these chemical signals. The overactive protein may contribute to the development of Langerhans cell histiocytosis by allowing the Langerhans cells to grow and divide uncontrollably. Changes in other genes have also been identified in the Langerhans cells of some individuals with Langerhans cell histiocytosis. Some researchers believe that additional factors, such as viral infections and environmental toxins, may also influence the development of this complex disorder. ### Learn more about the genes associated with Langerhans cell histiocytosis * BRAF * MAP2K1 * MAP3K1 ## Inheritance Pattern Langerhans cell histiocytosis is usually not inherited and typically occurs in people with no history of the disorder in their family. A few families with multiple cases of Langerhans cell histiocytosis have been identified, but the inheritance pattern is unknown. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Langerhans cell histiocytosis

c0019621

medlineplus

https://medlineplus.gov/genetics/condition/langerhans-cell-histiocytosis/

{"gard": ["6858"], "mesh": ["D006646"], "omim": ["604856"], "synonyms": []}

Female restricted epilepsy with intellectual disability is a rare X-linked epilepsy syndrome characterized by febrile or afebrile seizures (mainly tonic-clonic, but also absence, myoclonic, and atonic) starting in the first years of life and, in most cases, developmental delay and intellectual disability of variable severity. Behavioral disturbances (e.g. autistic features, hyperactivity, and aggressiveness) are also frequently associated. This disease affects exclusively females, with male carriers being unaffected, despite an X-linked inheritance. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Female restricted epilepsy with intellectual disability

c1848137

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101039

{"gard": ["10806"], "mesh": ["C564715"], "omim": ["300088"], "umls": ["C1848137"], "synonyms": ["EFMR", "Juberg-Hellman syndrome"]}

A rare neuro-ophthalmological disease associating the typical optic atrophy with other extra-ocular manifestations such as sensorineural deafness, myopathy, chronic progressive external ophthalmoplegia, ataxia and peripheral neuropathy. More rarely, other manifestations have been associated with this condition, such as spastic paraplegia or multiple-sclerosis like illness. ## Epidemiology Autosomal dominant optic atrophy plus syndrome (ADOA plus) accounts for approximately 20% of all ADOA cases. ## Clinical description ADOA plus is characterized by bilateral and symmetric progressive visual loss (visual acuity ranging from 20/30 to 20/200) and color vision deficiency, occurring typically during the first decade of life. Sensorineural deafness usually occurs later, during the second or third decade of life, although it may also be diagnosed, in rare instances, prior to the optic neuropathy. From the third decade onwards, other extra-ocular manifestations may appear, such as chronic progressive external ophthalmoplegia, proximal myopathy, ataxia and axonal sensory motor polyneuropathy. Other manifestations have been more rarely associated with ADOA plus, such as multiple sclerosis-like illness, migraine, cardiomyopathy, late-onset diabetes mellitus, and spastic paraplegia. ## Etiology ADOA plus is caused by mutations in the OPA1 gene (3q29), encoding a dynamin-like GTPase involved in the fusion of the inner mitochondrial membrane, in energetic production and mitochondrial DNA stability. ## Diagnostic methods Ophthalmological examination is not specific and typically shows a moderate bilateral optic atrophy associated with bilateral central or paracentral scotomas. Diagnosis of ADOA plus relies both on the genetic screening of the OPA1 gene and on skeletal muscle biopsy to measure the enzymatic activity of the respiratory chain complexes, allowing histological examination (Gomori-modified trichrome and double cytochrome C oxidase/succinate dehydrogenase staining) which typically reveals features of mitochondrial myopathy (cytochrome C negative fibers and ragged red fibers). Laboratory findings may reveal hyperlactacidemia. Additional investigations may include an audiological work-up, peripheral nerve conduction studies, electromyography, electroencephalography, brain magnetic resonance imaging, according to the patient's symptoms. ## Differential diagnosis Differential diagnosis includes several other syndromic hereditary optic neuropathies that may have bilateral manifestations associated with extra ocular features and that presents with a similar phenotype, such as Autosomal dominant Charcot-Marie-Tooth disease type 2A, Leber hereditary optic neuropathy, Wolfram syndrome and Wolfram-like syndrome. ## Antenatal diagnosis Prenatal identification of a mutation may be proposed in families with previously known mutations, with the understanding that not all the carriers will manifest the disease. ## Genetic counseling Transmission is autosomal dominant with variable penetrance and genetic counselling is recommended. ## Management and treatment There is currently no efficient treatment for ADOA plus. Low-vision aids may be recommended and cochlear implants have been shown to improve audition in patients with sensorineural deafness. The role of idebenone has been anecdotally reported in ADOA. Physiotherapy for the muscular symptoms programs can be warranted for patients with multiple sensory and motor handicaps. Avoiding tobacco and alcohol intake as well as medications interfering with mitochondrial metabolism (certain antibiotics, antivirals) is recommended. ## Prognosis Vision seems to be more severely affected in patients with ADOA plus than in patients with no extra ocular involvement. If associated, hearing loss can further impair social communication. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Autosomal dominant optic atrophy plus syndrome

c1832466

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1215

{"gard": ["5243"], "mesh": ["C535351"], "omim": ["125250", "165199", "616648"], "umls": ["C1832466"], "icd-10": ["H47.2"], "synonyms": ["DOA+", "Optic atrophy-deafness-polyneuropathy-myopathy syndrome", "Optic atrophy-hearing loss-polyneuropathy-myopathy syndrome"]}

Cobb syndrome is defined by the association of vascular cutaneous (venous or arteriovenous), muscular (arteriovenous), osseous (arteriovenous) and medullary (arteriovenous) lesions at the same metamere or spinal segment. This segmental distribution may involve one or many of the 31 metameres present in humans. Only 16% of the medullary lesions are multiple and have a clearly metameric distribution. ## Epidemiology Less than 100 cases of Cobb syndrome have been reported in the literature. There is no sex predilection. Cobb syndrome represents less than 15% of cases of spinal cord arteriovenous malformations. ## Clinical description The neurological symptomatology is comparable to that observed with acute haemorrhagic accidents or with chronic venous congestion of the spinal cord. The extent of the associated deficit depends on the localisation (cervical, thoracic, lumbar or sacral). These manifestations most often involve the lower limbs and are characterised by bilateral motor or sensory asymmetric deficits associated with sphincter anomalies. The morphological manifestations may be partial (appearing incomplete) in cases were some of the localisations at the same metamere are absent. The cutaneous manifestations of the syndrome are most often flat vascular lesions (port-wine stains) but angiokeratomas, angiolipomas and lymphangiomas have been reported. The medullary lesions are arteriovenous malformations. The muscular and osseous lesions may cause nonmechanical localised pain but are often asymptomatic. ## Etiology The syndrome is not familial or hereditary and no chromosomal anomaly has been described. The primitive events causing the disorder occur during early embryogenesis and involve a group of precursor vascular cells before the stage of migration to their definitive cell territories (skin, bone, peripheral nerve or spinal cord). Two consecutive territories may be affected resulting in multimetameric forms of the disease. Recent analysis of Cobb syndrome has led to use of the term Spinal Arteriovenous Metameric Syndrome 1-31 (SAMS 1-31), by analogy with the Cerebrofacial Arteriovenous Metameric Syndromes (CAMS 1-3) and the Cerebrofacial venous metameric syndromes (CVMS1-3). ## Diagnostic methods Diagnosis is made by MRI, supplemented by medullary angiography. ## Management and treatment Treatment of the osteomuscular malformations involves embolisation (endovascular navigation and occlusion of the arteries feeding the malformation using a biological glue) and/or surgery. Laser treatment is used for associated superficial cutaneous lesions. Radicular or medullary malformations are treated by embolisation. Indications for classic surgery are restricted to certain localisations and superficial lesions, epidural and paraspinal injections can be used if the endovascular approach fails. Radiotherapy is not indicated. Early diagnosis reduces the extent of the neurological deterioration, in particular paralysis. ## Prognosis The disease course is unpredictable and the lesions may remain asymptomatic for long periods of time. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Spinal arteriovenous metameric syndrome

c0346068

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=53721

{"gard": ["11892"], "umls": ["C0346068"], "icd-10": ["Q27.3"], "synonyms": ["Cobb syndrome", "Cutaneomeningospinal angiomatosis", "SAMS 1-31"]}

Ochoa syndrome is a very rare condition that causes unusual facial expressions and problems with urination. People with this condition have a characteristic frown-like facial expression when they try to smile or laugh, often described as "inversion" of facial expression. Urinary tract problems may include the inability to control urination (incontinence), inability to completely empty the bladder, and the buildup of urine in the kidneys (hydronephrosis). These problems often start in early childhood or adolescence and may lead to eventual kidney failure. Other signs and symptoms may include constipation, loss of bowel control and/or muscle spasms of the anus. Ochoa syndrome can be caused by a non-working HPSE2 or LRIG2 gene and is inherited in an autosomal recessive manner. It can be diagnosed based on the symptoms. Treatment may involve surgery, antibiotics and medications to decrease bladder hyperactivity. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Ochoa syndrome

c0403555

gard

https://rarediseases.info.nih.gov/diseases/104/ochoa-syndrome

{"mesh": ["C536480"], "omim": ["236730"], "umls": ["C0403555"], "orphanet": ["2704"], "synonyms": ["Hydronephrosis with peculiar facial expression", "Urofacial syndrome", "Inverted smile and occult neuropathic bladder", "Partial facial palsy with urinary abnormalities", "Urofacial Ochoa's syndrome", "UFS"]}

The examples and perspective in this article deal primarily with the United Kingdom and do not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (March 2018) (Learn how and when to remove this template message) Alabama rot or cutaneous and renal glomerular vasculopathy (CRGV)[1] is an often fatal condition in dogs. It was first identified in the US in the 1980s in greyhounds.[2][3] The initial symptoms are skin lesions on the legs, chest and abdomen followed by renal involvement.[2][3] In November 2012 the first cases were suspected in the UK.[4] In January 2014, the outbreak in England was identified as having the same or similar histological and clinical findings as Alabama rot, though this could not be classified as Alabama Rot as the histological results from the UK lacked the relation to E. coli that was present in all the cases in the US,[1][2] although a wide range of breeds were affected.[1] The suspected disease has been possibly identified across England and Wales, with a case being reported as far north as North Yorkshire in March 2015. A UK map posted online shows confirmed (with post-mortem) and unconfirmed (without post-mortem) cases of CRGV since December 2012.[5] In May 2017 it was reported that 98 suspected deaths from the disease have occurred in the UK, including 15 in 2017.[6] Local residents report 6 vet reported deaths in the Rivington area in Winter 2017/18 with 2 dogs still to have autopsies. One ongoing local study in 2018 finds a lethal outbreak following the escape of wormed deer in Adlington, England, of deer deemed unfit for human food. With no wormer maintained, bacteria or parasites could have spread naturally especially towards predatory breeds.[7] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Treatments * 4 Epidemiology * 5 References ## Signs and symptoms[edit] The disease is characterized by cutaneous and sometimes renal changes with the latter frequently being ultimately fatal.[8][3] Common symptoms of CRGV include, but are not limited to:[9] * Cutaneous lesions involving erythema, erosion, ulceration occurring mainly on extremities such as distal limbs, muzzle and ventrum * Pyrexia (fever) * Lethargy or malaise * Anorexia * Vomiting or retching ## Causes[edit] Some veterinary experts theorize the disease is caused by a parasite, while others believe it is bacterial. It is more widely believed that Alabama rot is caused by toxins produced by E. coli but, as there has been no presence of E. coli in histological examination in UK cases, the disease is described there as suspected CRGV rather than Alabama rot per se. Because the exact cause has not been found, developing a vaccine is not possible. The cause of Alabama rot in the UK is under study as of 2013 at Anderson Moores Veterinary Specialists in Winchester, Hampshire, but they do not explain why they are calling it Alabama Rot and not CRGV in accordance with histological findings.[10] A podcast on Alabama rot was published in April 2014 by the Royal Veterinary College.[11] As of February 2015 the Forestry Commission England will only publish specific site location details if "cases are confirmed as CRGV and a scientific connection to the dogs walked on the site is made".[12] A comprehensive report on CRGV was published in March 2015 by the British Veterinary Association, concluding that it is a disease of unknown cause "carrying a poor prognosis when azotaemia develops".[13] However, an association has been linked to dogs walking on muddy ground.[14] ## Treatments[edit] Treatment is primarily symptomatic involving wound management of skin lesions and aggressive supportive therapy when renal compromise occurs. Some UK dogs with Alabama rot have been successfully treated since 2013.[10] A webinar on Alabama rot by the Royal Veterinary College on 11 February 2015 was tutored by David Walker of Anderson Moores Veterinary Specialists.[15] As the disease is widely believed to spread via dogs' feet and legs, due to the current lack of treatment the best action is to avoid infection by not walking dogs in a suspected infected area.[citation needed] In August 2018 sources reported that plasmapheresis (therapeutic plasma exchange) resulted in survival of 2 out of 6 dogs with advanced disease.[16] This finding offers hope that such blood filtering could result in better survival rates, particularly if caught early before vascular and renal damage occur. ## Epidemiology[edit] The number of cases in the US is not known, but it was confined to greyhounds and in many cases was not fatal; however, as of 2017 there had been 103 suspected cases in the UK.[17] ## References[edit] 1. ^ a b c "Signs warn dog owners of killer disease". BBC Online. 21 January 2014. Retrieved 27 March 2015. 2. ^ a b c "What is Alabama rot?". The Daily Telegraph. 21 January 2014. Retrieved 27 March 2015. 3. ^ a b c Carpent, J. L.; et al. (1988). "Idiopathic Cutaneous and Renal Glomerular Vasculopathy of Greyhounds". Veterinary Pathology. 25 (6): 401–407. doi:10.1177/030098588802500601. PMID 3212884. 4. ^ Walker, D (23 March 2015). Important information regarding dogs with acute kidney injury ('Alabama Rot'). Anderson Moores Veterinary Specialists. Retrieved 27 March 2015. 5. ^ "UK Map of Alabama Rot". 6 February 2015. Retrieved 27 March 2015. 6. ^ Jennifer Scott (10 May 2017). "Alabama rot: The dog disease with no cure". BBC News. Retrieved 29 November 2017. 7. ^ Primary research, Parasite? Rivington & Aspull, Dog Death Phenomenon Study, Galway & Jackson Animal Welfare, 2018 8. ^ Holm, L. P.; Hawkins, I.; Robin, C.; Newton, R. J.; Jepson, R.; Stanzani, G.; McMahon, L. A.; Pesavento, P.; Carr, T. (2015-04-11). "Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK". Veterinary Record. 176 (15): 384. doi:10.1136/vr.102892. ISSN 0042-4900. PMC 4413843. PMID 25802439. 9. ^ "Symptoms". www.arrf.co.uk Alabama Rot Research Fund (ARRF). Retrieved 26 May 2020. 10. ^ a b "Important information regarding dogs with acute kidney injury ('Alabama Rot')". Anderson Moores. Retrieved 28 March 2015. 11. ^ Jasani, S. (14 April 2014). Alabama Rot-like Syndrome in UK dogs (and podcast). Royal Veterinary College. Retrieved 28 March 2015. 12. ^ "Cutaneous and Renal Glomerular Vasculopathy (CRGV or 'Alabama Rot')". Forestry Commission England. Retrieved 28 March 2015. 13. ^ Holm, L. P.; et al. (March 2015). "Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK". Veterinary Record. 176 (15): 384. doi:10.1136/vr.102892. PMC 4413843. PMID 25802439. Retrieved 24 March 2015. 14. ^ "Alabama rot". www.thekennelclub.org.uk. Retrieved 26 May 2020. 15. ^ "Webinar: Understanding 'Alabama Rot'". Royal Veterinary College. 11 February 2015. Archived from the original on 4 March 2016. Retrieved 28 March 2015. 16. ^ RVC announces Alabama rot breakthrough 1 August 2018 www.vettimes.co.uk, accessed 26 May 2020 17. ^ UK Alabama Rot risk may be linked to certain types of dog breed and habitat, BMJ Newsroom, accessed 26 May 2020 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Alabama rot

None

wikipedia

https://en.wikipedia.org/wiki/Alabama_rot

{"wikidata": ["Q16826773"]}

This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (May 2019) This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (November 2018) (Learn how and when to remove this template message) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Helsmoortel-Van der Aa syndrome" – news · newspapers · books · scholar · JSTOR (November 2018) (Learn how and when to remove this template message) (Learn how and when to remove this template message) Helsmoortel-Van der Aa syndrome Autosomal dominant pattern is the inheritance manner of this condition SpecialtyMedical genetics Helsmoortel-Van der Aa syndrome is a condition caused by mutations in the activity-dependent neuroprotector homeobox (ADNP) gene.[1] This condition is rare with <100 cases described up to 2018. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Pathogenesis * 4 Diagnosis * 5 Treatment * 6 History * 7 References ## Signs and symptoms[edit] These are variable and include autism spectrum disorders, intellectual disability, dysmorphic features and hypotonia. ## Genetics[edit] This condition is caused by mutations in the ADNP gene. This gene is located on the long arm of chromosome 20 (20q13.13). ADNP has been associated with abnormalities in the autophagy pathway in schizophrenia.[2] ## Pathogenesis[edit] The ANDP gene is involved in the autophagy pathway. Its precise role in this process is under active investigation. ## Diagnosis[edit] This is made by sequencing the ADNP gene. ## Treatment[edit] Treatment is symptomatic. This may include speech, occupational, and physical therapy and specialized learning programs depending on individual needs. Treatment of neuropsychiatric features may also be needed. Nutritional support is sometimes needed. Treatment of the ophthalmologic and cardiac finding that may co exist is also indicated. ## History[edit] The gene was described in 1999. ## References[edit] 1. ^ Van Dijck A, Vulto-van Silfhout AT, Cappuyns E, van der Werf IM, Mancini GM, Tzschach A, et al. (March 2018). "Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP". Biological Psychiatry. 85 (4): 287–297. doi:10.1016/j.biopsych.2018.02.1173. PMC 6139063. PMID 29724491. 2. ^ Sragovich S, Merenlender-Wagner A, Gozes I (November 2017). "ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer's Disease". BioEssays. 39 (11): 1700054. doi:10.1002/bies.201700054. PMID 28940660. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Helsmoortel-Van der Aa syndrome

c4014538

wikipedia

https://en.wikipedia.org/wiki/Helsmoortel-Van_der_Aa_syndrome

{"gard": ["12931"], "umls": ["C4014538"], "orphanet": ["404448"], "wikidata": ["Q50349632"]}

A number sign (#) is used with this entry because of evidence that alpha-thalassemia is caused by mutations in the alpha-globin genes (HBA1, 141800; HBA2, 141850). Sequences 30 to 50 kb upstream from the alpha-globin gene cluster, referred to as the locus control region alpha (LCRA; 152422), have been found to be deleted in cases of alpha-thalassemia with structurally intact alpha-globin genes. The molecular and clinical aspects of the severe alpha-thalassemia syndromes were reviewed by Higgs (1993) and Chui and Waye (1998). Weatherall (2001) reviewed phenotype-genotype relationships in monogenic diseases based on studies of the thalassemias. The remarkable phenotypic diversity of the beta-thalassemias reflects the heterogeneity of mutations at the HBB locus, the action of many secondary and tertiary modifiers, and a wide range of environmental factors. Weatherall (2001) stated that phenotype-genotype relations will likely be equally complex in many monogenic diseases. The findings reviewed by Weatherall (2001) highlighted the problems that might be encountered in defining the relationship between the genome and the environment in multifactorial disorders, in which the degree of heritability may be relatively low and several environmental agents are involved. Molecular Genetics For a review of mutations in the HBA genes causing alpha-thalassemia, see 141800 and 141850. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

ALPHA-THALASSEMIA

c0002312

omim

https://www.omim.org/entry/604131

{"doid": ["1099"], "mesh": ["D017085"], "omim": ["604131"], "icd-9": ["282.43"], "icd-10": ["D56.0"], "orphanet": ["846"], "genereviews": ["NBK1435"]}

This article is about the personality trait characterizing highly sensitive persons (HSPs). For the distinct but similarly-named disorder, see Sensory processing disorder. Characteristics of SPS as graphically summarized by Greven et al. (review article, 2019)[1] A person with a high measure of SPS is said to be a highly sensitive person (HSP).[2][3] Part of a series on Psychology * Outline * History * Subfields Basic types * Abnormal * Behavioral genetics * Biological * Cognitive/Cognitivism * Comparative * Cross-cultural * Cultural * Differential * Developmental * Evolutionary * Experimental * Mathematical * Neuropsychology * Personality * Positive * Quantitative * Social Applied psychology * Applied behavior analysis * Clinical * Community * Consumer * Counseling * Critical * Educational * Environmental * Ergonomics * Forensic * Health * Humanistic * Industrial and organizational * Legal * Medical * Military * Music * Occupational health * Political * Religion * School * Sport * Traffic Lists * Disciplines * Organizations * Psychologists * Psychotherapies * Publications * Research methods * Theories * Timeline * Topics * Psychology portal * v * t * e Sensory processing sensitivity (SPS) is a temperamental or personality trait involving "an increased sensitivity of the central nervous system and a deeper cognitive processing of physical, social and emotional stimuli".[2] The trait is characterized by "a tendency to 'pause to check' in novel situations, greater sensitivity to subtle stimuli, and the engagement of deeper cognitive processing strategies for employing coping actions, all of which is driven by heightened emotional reactivity, both positive and negative".[3] A human with a particularly high measure of SPS is considered to have 'hypersensitivity', or be a highly sensitive person (HSP).[2][3] The terms SPS and HSP were coined in the mid-1990s by psychologists Elaine Aron and her husband Arthur Aron, who developed the Highly Sensitive Person Scale (HSPS) questionnaire by which SPS is measured.[3] Other researchers have applied various other terms to denote this responsiveness to stimuli that is seen in humans and other species.[4] According to the Arons and colleagues, people with high SPS make up about 15–20% of the population.[2] Although some researchers consistently related high SPS to negative outcomes,[3][5] other researchers have associated it with increased responsiveness to both positive and negative influences.[6][7][8][9] Aron and colleagues state that the high-SPS personality trait is not a disorder.[10][11] ## Contents * 1 Origin and development of the terms * 1.1 Earlier research * 2 Attributes, characteristics and prevalence * 3 See also * 4 Sources and notes * 5 External links ## Origin and development of the terms[edit] Elaine Aron's book The Highly Sensitive Person was published in 1996.[12] In 1997 Elaine and Arthur Aron formally identified[13] sensory processing sensitivity (SPS) as the defining trait of highly sensitive persons (HSPs).[3] The popular terms hypersensitivity (not to be confused with the medical term hypersensitivity) or highly sensitive are popular synonyms for the scientific concept of SPS.[2] By way of definition, Aron and Aron (1997) wrote that sensory processing here refers not to the sense organs themselves, but to what occurs as sensory information is transmitted to or processed in the brain.[13] They assert that the trait is not a disorder but an innate survival strategy that has both advantages and disadvantages.[10][11] Elaine Aron's academic journal articles as well as self-help publications for the lay reader have focused on distinguishing high SPS from socially reticent behavior[14] and disorders[11][15] with which high SPS can be confused;[16] overcoming the social unacceptability that can cause low self-esteem;[16] and emphasizing the advantages of high SPS[17] to balance the disadvantages emphasized by others.[5][16][18] In 2015, sociologist Elizabeth Bernstein wrote in The Wall Street Journal that HSPs were "having a moment," noting that several hundred research studies had been conducted on topics related to HSPs' high sensitivity. The First International Scientific Conference on High Sensitivity or Sensory Processing Sensitivity was held at the Vrije Universiteit Brussel.[19] By 2015, more than a million copies of The Highly Sensitive Person had been sold.[20] ### Earlier research[edit] Research pre-dating the Arons' coining of the term "high sensitivity" includes that of German medicine professor Wolfgang Klages, who argued in the 1970s that the phenomenon of sensitive and highly sensitive humans is "biologically anchored" and that the "stimulus threshold of the thalamus" is much lower in these persons.[21] As a result, said Klages, there is a higher permeability for incoming signals from afferent nerve fibers so that they pass "unfiltered" to the cerebral cortex.[21] The Arons (1997) recognized psychologist Albert Mehrabian's (1976, 1980, 1991) concept of filtering the "irrelevant", but wrote that the concept implied that the inability of HSPs' (Mehrabian's "low screeners") to filter out what is irrelevant would imply that what is relevant is determined from the perspective of non-HSPs ("high screeners").[13] ## Attributes, characteristics and prevalence[edit] Boterberg et al. (2016) describe high SPS as a "temperamental or personality trait which is present in some individuals and reflects an increased sensitivity of the central nervous system and a deeper cognitive processing of physical, social and emotional stimuli".[2] People with high SPS report having a heightened response to stimuli such as pain, caffeine, hunger, and loud noises.[5] According to Boterberg et al., these individuals are "believed to be easily overstimulated by external stimuli because they have a lower perceptual threshold and process stimuli cognitively deeper than most other people."[2] This deeper processing may result in increased reaction time as more time is spent responding to cues in the environment, and might also contribute to cautious behavior and low risk-taking.[2] SPS involves responsiveness to both environmental adversity and positive environmental aspects, respectively modeled by the diathesis-stress model and the vantage sensitivity framework.[22] The HSP Scale, initially (1997) a questionnaire designed to measure SPS on a unidimensional scale, was subsequently decomposed into two,[23][24] three,[25] or four[26] factors or sub-scales.[2] Most components have been associated with traditionally accepted negative psychological outcomes[2][3] including high stress levels, being easily overwhelmed, increased rates of depression, anxiety, and sleep problems, as well as symptoms of autism;[2] the diathesis-stress model focused on increased vulnerability to negative influences.[6] However, the differential susceptibility theory (DST)[6][7] and biological sensitivity to context theory (BSCT)[8] and sensory processing sensitivity (SPS)[27] suggest increased plasticity in terms of responsiveness to both positive and negative influences; and the vantage sensitivity (VS) concept emphasizes increased responsiveness to positive experiences.[9][28]Researchers such as Smolewska et al. (2006) said positive outcomes were more common in individuals with high aesthetic sensitivity, who tend to experience heightened positive emotions in response to rewarding stimuli and more likely to score high on "openness" on the Big Five factors model.[29] Research in evolutionary biology provides evidence that the trait of SPS can be observed, under various terms, in over 100 nonhuman species,[2][4] Aron writing that the SPS trait is meant to encompass what personality psychologists have described under various other names.[30] Conversely, Aron has distinguished SPS from what she considers it is not, explicitly distinguishing[31] high SPS from possibly similar-appearing traits or disorders (such as shyness,[16][32] sensation-seeking,[33] sensory processing disorder,[15] and autism[10]), and further, that SPS may be a basic variable that may underlie multiple other trait differences[13] (such as introversion versus extraversion[31]). Contrary to common misconception, according to Aron HSPs include both introverts and extroverts,[34] and may be simultaneously high-sensation seeking and cautious.[33] In humans and other species, responsive and unresponsive individuals coexist and consistently display different levels of responsiveness to environmental stimuli, the different levels of responsiveness having corresponding evolutionary costs and benefits.[4] This observation parallels Aron's assertion that high SPS is not a disorder, but rather a personality trait with attendant advantages and disadvantages.[10][11] Accordingly, Aron cautions medical professionals against prescribing psychoactive medications to "cure" the trait, which may or may not coexist with an actual disorder.[35] By 2015 the trait had been documented at various levels of study, including temperament and behavior psychology, brain function and neuronal sensitization, and genetics.[7] For example, genetic studies provide evidence that higher levels of SPS are linked to the serotonin transporter 5-HTTLPR short/short genotype,[36] polymorphisms in dopamine neurotransmitter genes,[37] and the ADRA2b norepinephrine-related gene variant.[38] HSP Scale score patterns in adults were thought to be distributed as a dichotomous categorical variable with a break point between 10% and 35%,[15] with Aron choosing a cut-off of the highest-scoring 20% of individuals to define the HSP category.[2] A 2019 review article stated that findings suggest people fall into three sensitivity groups along a normal distribution sensitivity continuum.[1] ## See also[edit] * Differential susceptibility hypothesis * Environmental sensitivity * Evolutionary psychology * Neuropsychology * Neuroticism * Personality psychology * Sensory processing * Social psychology * Trait theory * Cognition * Executive functions * Development of the nervous system * Cultural neuroscience * Neurodiversity ## Sources and notes[edit] 1. ^ a b Greven, Corina U.; Lionetti, Francesca; Booth, Charlotte; Aron, Elaine N.; Fox, Elaine; Schendan, Haline E.; Pluess, Michael; Bruining, Hilgo; Acevedo, Bianca; Bijttebier, Patricia; Homberg, Judith (March 2019). "Sensory Processing Sensitivity in the context of Environmental Sensitivity: A critical review and development of research agenda (Review article)". Neuroscience and Biobehavioral Reviews. Elsevier. 98: 287–305. doi:10.1016/j.neubiorev.2019.01.009. PMID 30639671. 2. ^ a b c d e f g h i j k l m Boterberg, Sofie; Warreyn, Petra (2016), "Making sense of it all: The impact of sensory processing sensitivity on daily functioning of children", Personality and Individual Differences, 92: 80–86, doi:10.1016/j.paid.2015.12.022, hdl:1854/LU-7172755, archived from the original on May 23, 2016 3. ^ a b c d e f g Booth, Charlotte; Standage, Helen; Fox, Elaine (1 Dec 2015), "Sensory-processing sensitivity moderates the association between childhood experiences and adult life satisfaction", Personality and Individual Differences, 87: 24–29, doi:10.1016/j.paid.2015.07.020, PMC 4681093, PMID 26688599 4. ^ a b c Wolf, Max; Van Doorn, G. Sander; Weissing, Franz J. (2008). "Evolutionary emergence of responsive and unresponsive personalities". PNAS. 105 (41): 15825–15830. doi:10.1073/pnas.0805473105. PMC 2572984. PMID 18838685. "Such differences in responsiveness (also termed coping style, reactivity, flexibility, plasticity) have been documented in many organisms including ... humans" (n. 15 citing Aron & Aron (1997, SPS) and n. 16 citing Belsky et al. (2007, differential susceptibility)). Boterberg et al. (2016) cites Wolf et al. (2008) for the statement: "research in evolutionary biology provides evidence that the trait of SPS can be observed in over 100 nonhuman species." 5. ^ a b c Liss, Miriam; Mailloux, Jennifer; Erchull, Mindy J. (2008), "The relationships between sensory processing sensitivity, alexithymia, autism, depression, and anxiety" (PDF), Personality and Individual Differences, 45 (3): 255–259, doi:10.1016/j.paid.2008.04.009, archived (PDF) from the original on May 23, 2016 6. ^ a b c Belsky, Jay; Pluess, Michael (2009). "Beyond Diathesis Stress: Differential Susceptibility to Environmental Influences" (PDF). Psychological Bulletin. 135 (6): 885–908. doi:10.1037/a0017376. PMID 19883141. Archived from the original (PDF) on December 7, 2010. Retrieved January 28, 2016. 7. ^ a b c Boyce, W. Thomas (2016). "Differential Susceptibility of the Developing Brain to Contextual Adversity and Stress". Neuropsychopharmacology. 41 (1): 141–162. doi:10.1038/npp.2015.294. PMC 4677150. PMID 26391599. "(T)here is an emerging scientific consensus on how 'sensitivity to context' may be instantiated with an intricate and compelling neuroscience" (p. 149). "... a now substantial corpus of evidence ... documenting differences in susceptibility at the levels of temperament and behavior ("The Highly Sensitive Person at p. 146), neuroendocrine physiology, brain structure and function ("Cortical sensory processing sensitivity" at p. 149), neuronal sensitization and responsivity, and allelic and epigenetic variation within genomic structure" (p. 157). 8. ^ a b Boyce, W. Thomas; Ellis, Bruce J. (2005). "Biological sensitivity to context: I. An evolutionary–developmental theory of the origins and functions of stress reactivity". Development and Psychopathology. 17 (2): 271–301. doi:10.1017/S0954579405050145. PMID 16761546. Archived (PDF) from the original on October 20, 2017. "Aron and Aron (1997, p. 362) provide an important further elucidation of the reactivity construct in their discussion of sensory-processing sensitivity" (p. 286). 9. ^ a b Pluess, Michael; Belsky, Jay (2013). "Vantage Sensitivity: Individual Differences in Response to Positive Experiences" (PDF). Psychological Bulletin. 139 (4): 901–916. doi:10.1037/a0030196. PMID 23025924. Archived (PDF) from the original on January 26, 2016. 10. ^ a b c d Aron, E.N. (2006). "The Clinical Implications of Jung's Concept of Sensitiveness". Journal of Jungian Theory and Practice. 8: 11–43. CiteSeerX 10.1.1.490.9371. Discussion re nervous system is, inter alia, in "Prelude to Research" at p. 14. 11. ^ a b c d Acevedo, B; Aron, E; Pospos, S; Jessen, D (April 2018). "The functional highly sensitive brain: a review of the brain circuits underlying sensory processing sensitivity and seemingly related disorders". Phil. Trans. R. Soc. B. 373 (1744): 20170161. doi:10.1098/rstb.2017.0161. PMC 5832686. PMID 29483346. "(I)n this review, we compare the neural regions implicated in SPS with those found in fMRI studies of Autism Spectrum Disorder (ASD), Schizophrenia (SZ) and Post-Traumatic Stress Disorder (PTSD) to elucidate the neural markers and cardinal features of SPS versus these seemingly related clinical disorders. We propose that SPS is a stable trait that is characterized by greater empathy, awareness, responsivity and depth of processing to salient stimuli. We conclude that SPS is distinct from ASD, SZ and PTSD in that in response to social and emotional stimuli, SPS differentially engages brain regions involved in reward processing, memory, physiological homeostasis, self-other processing, empathy and awareness. We suggest that this serves species survival via deep integration and memory for environmental and social information that may subserve well-being and cooperation." 12. ^ Kaufman, Scott Barry (May 4, 2015). "Shades of Sensitivity". Scientific American. Archived from the original on December 8, 2015. Kaufman explains Smolewska et al. (2006). 13. ^ a b c d Aron, Elaine; Aron, Arthur (1997). "Sensory-Processing Sensitivity and its Relation to Introversion and Emotionality" (PDF). Journal of Personality and Social Psychology. 73 (2): 345–368. doi:10.1037/0022-3514.73.2.345. PMID 9248053. Archived (PDF) from the original on May 13, 2015. 14. ^ Chen, Xinyin; Rubin, Kenneth H.; Sun, Yuerong (1992). "Social Reputation and Peer Relationships in Chinese and Canadian Children: A Cross-cultural Study". Child Development. 63 (6): 1336–1343. doi:10.1111/j.1467-8624.1992.tb01698.x. Archived (PDF) from the original on February 4, 2016. 15. ^ a b c Aron, E.; Aron, A.; Jagiellowicz, J. (2012). "Sensory processing sensitivity: A review in the light of the evolution of biological responsivity" (PDF). Personality and Social Psychology Review. 16 (3): 262–282. doi:10.1177/1088868311434213. PMID 22291044. S2CID 2542035. Archived (PDF) from the original on May 13, 2015. 16. ^ a b c d Aron, E. N.; Aron, A.; Davies, K. (2005). "Adult shyness: The interaction of temperamental sensitivity and an adverse childhood environment" (PDF). Personality and Social Psychology Bulletin. 31 (2): 181–197. doi:10.1177/0146167204271419. PMID 15619591. S2CID 1679620. Note 3 (p. 195) cites Chen et al. (1992) re social and cultural unacceptability adding to environmental stressors. 17. ^ Rioux, Charlie; Castellanos-Ryan, Natalie; Parent, Sophie; Bitaro, Frank; Tremblay, Richard E.; Seguin, Jean R. (2016). "Differential susceptibility to environmental influences: Interactions between child temperament and parenting in adolescent alcohol use". Dev. Psychopathol. 28 (1): 265–275. doi:10.1017/S0954579415000437. PMC 4676730. PMID 26030853. "From a clinical perspective, Aron (2010) adds that while sensitive people may be more vulnerable, sensitivity is not only a liability but also may confer advantages." 18. ^ Belsky, J.; Jonassaint, C; Pluess, M; Stanton, M; Brummett, B; Williams, R (2009). "Vulnerability genes or plasticity genes?" (PDF). Molecular Psychiatry. 14 (8): 746–754. doi:10.1038/mp.2009.44. PMC 2834322. PMID 19455150. Archived from the original (PDF) on June 6, 2012. Retrieved January 28, 2016. 19. ^ Bernstein, Elizabeth (May 18, 2015). "Do You Cry Easily? You May Be a 'Highly Sensitive Person'". The Wall Street Journal. Archived from the original on June 1, 2015. 20. ^ Lally, Maria (October 12, 2015). "Highly sensitive people: a condition rarely understood". The Telegraph. U.K. Archived from the original on October 18, 2015. 21. ^ a b Klages, Wolfgang (1978). Der sensible Mensch : Psychologie, Psychopathologie, Therapie (The Sensitive Human: Psychology, Psychopathology, Therapy) (in German) (1 ed.). Stuttgart, Germany: Enke. p. 133. ISBN 978-3432898711. OCLC 6710563. Klages distinguishes between sensitive and highly sensitive people, classifying artists and "high intellectuals" as an example of the latter. 22. ^ Pluess, Michael (September 2015). "Individual Differences in Environmental Sensitivity". Child Development Perspectives. 9 (3): 138–143. doi:10.1111/cdep.12120. "...per- haps the most significant contribution shared across all three frameworks [SPS and DST, BSC] is the notion that sensitive individuals differ not only in their response to environmental adversity but also in response to positive, supportive aspects of the environment". 23. ^ Evans, David E.; Rothbart, Mary K. (January 2008). "Temperamental sensitivity: Two constructs or one?" (PDF). Personality and Individual Differences. 44 (1): 108–118. doi:10.1016/j.paid.2007.07.016. Archived from the original (PDF) on February 7, 2016. Retrieved February 7, 2016. Negative affectand orienting sensitivity. 24. ^ Boterberg et al. (2016): overreaction to stimuli (OS) and depth of processing (DP). 25. ^ Smolewska et al. (2006): Aesthetic Sensitivity (AES, having greater awareness of beauty), Low Sensory Threshold (LST, easily unpleasantly aroused by external stimuli), and Ease of Excitation (EOE, easily overwhelmed by stimuli); results showing the (unidimensional) HSP Scale was "a valid and reliable measure of the construct of SPS"). Liss et al. (2008). 26. ^ Per Boterberg et al. (2016), a "theoretical redefinition" by E. Aron, Psychotherapy and the Highly Sensitive Person (2010): "DOES" acronym: Depth of processing, Overstimulation, Emotional intensity, Sensory sensitivity. 27. ^ Ellis, Bruce J.; Boyce, W. Thomas; Belsky, Jay; Bakermans-Kranenburt, Marian J.; van Ijzendoorn, Marinus H. (2011). "Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory". Development and Psychopathology. 23 (1): 7–28. doi:10.1017/S0954579410000611. PMID 21262036. Archived from the original on July 4, 2016. "DST and BSCT began with a focus on child-developmental processes, whereas SPS started with a focus on cognitive processes in adults" (p. 10). 28. ^ Thibodeau, Eric L.; August, Gerald J.; Cicchetti, Dante; Symons, Frank J. (2016). "Application of environmental sensitivity theories in personalized prevention for youth substance abuse: a transdisciplinary translational perspective". Transl Behav Med. 6 (1): 81–89. doi:10.1007/s13142-015-0374-4. PMC 4807189. PMID 27012256. "Five distinct but related frameworks comprise ES (environmental sensitivity), including diathesis stress, differential susceptibility theory (DST), sensory processing sensitivity (SPS) [n. 22: A&A 1997], biological sensitivity to context (BSC) [n. 23: Boyce 2005], and vantage sensitivity (VS) [n. 24: Pluess 2013]". 29. ^ Smolewska, Kathy A.; McCabe, Scott B.; Woody, Erik Z. (2006). "A psychometric evaluation of the Highly Sensitive Person Scale: The components of sensory-processing sensitivity and their relation to the BIS/BAS and "Big Five"". Personality and Individual Differences. 40 (6): 1269–1279. doi:10.1016/j.paid.2005.09.022. See also Kaufman, Scientific American (2015). 30. ^ Paraphrasing Aron and citing Wolf re different names for same or equivalent concepts: * From "Adult shyness: ..." (2005): weak nervous system (Pavlov), low screening (Mehrabian), augmenting (of stimulation; Petrie), reducing (of evoked potential; Buchsbaum, Haier, & Johnson), reactivity (Strelau), avoidance temperament (Elliot & Thrash), and nondisinhibition or reflectivity (Patterson & Newman), and what child temperament researchers have described as inhibitedness (Kagan), infant (or innate) shyness (Cheek & Buss; Daniels & Plomin), reactivity (Rothbart; Strelau), and threshold of responsiveness (Thomas & Chess). * From "The Clinical Implications of Jung's Concept of Sensitiveness" (2006): innate sensitiveness (Jung), * From "Adult shyness: ..." (2005): arousal focus (Feldman), and the physiological differences underlying introversion and extroversion (Eysenck; Stelmack; Stelmack & Geen). * From Wolf et al. (2008): coping style, reactivity, flexibility, plasticity, and differential susceptibility. 31. ^ a b Paraphrasing Aron re what SPS is not: * From "'The Power of (Shyness)' and High Sensitivity..." (2012): (re introversion) 30% of HSPs are social extroverts. * From "Adult shyness: ..." (2005): SPS doesn't inherently possess shyness' fear of negative social evaluations. * From p. 2 of "The HSP in love" (<=2007): an HSP who is also a High Sensation Seeker will find ways to have novel experiences without taking ill-considered risks. * From "... A Review... " (2012): SPS is "unrelated to Sensory Processing Disorder" * From "The Clinical Implications of Jung's Concept of Sensitiveness" (2006): (re autism) HSPs are very aware of social and emotional cues and relate well socially once familiarity is achieved. 32. ^ Aron, Elaine N. (February 2, 2012). "Time Magazine: 'The Power of (Shyness)' and High Sensitivity". Psychology Today. Archived from the original on February 12, 2012. 33. ^ a b "The Highly Sensitive Person In Love with Elaine Aron". WebMD Live Events Transcript. Archived from the original on March 17, 2018. Transcript published October 2007 or before. 34. ^ Aron, Elaine N., Ph.D, "Understanding the Highly Sensitivity Person: Sensitive, Introverted, or Both? | Extraverted HSPs face unique challenges" (Archived April 19, 2013, at Archive.today) Psychology Today, July 21, 2011. 35. ^ Aron, Elaine N. (1996). "9. Medics, Medications and HSPs". The Highly Sensitive Person. Broadway Books. pp. 194–197. ISBN 9780806536705. Especially subsections "A Caution About Medical Labels for Your Trait" through "Instant Arousal-Stopping Medications". 36. ^ Licht, Cecile L.; Mortensen, Erik L.; Knudsen, Gitte M. (2011). "Association between Sensory Processing Sensitivity and the 5-HTTLPR Short/Short Genotype" (PDF). Center for integrated molecular brain imaging. Archived (PDF) from the original on June 6, 2012. ● Licht, C., Mortensen, E. L., & Knudsen, G. M. (2011). "Association between sensory processing sensitivity and the serotonin transporter polymorphism 5-HTTLPR short/short genotype." Biological Psychiatry, 69, supplement for Society of Biological Psychiatry Convention and Annual Meeting, abstract 510. 37. ^ Chen, C.; Chen, C.; Moyzis, R.; Stern, H.; He, Q.; Li, H.; Dong, Q. (2011). "Contributions of dopamine-related genes and environmental factors to Highly Sensitive Personality: A multi-step neuronal system-level approach". PLOS ONE. 6 (7): e21636. Bibcode:2011PLoSO...621636C. doi:10.1371/journal.pone.0021636. PMC 3135587. PMID 21765900. 38. ^ Todd, R. M.; Ehlers, M. R.; Muller, D. J.; Robertson, A.; Palombo, D. J.; Freeman, N.; Levine, B.; Anderson, A. K. (2015). "Neurogenetic Variations in Norepinephrine Availability Enhance Perceptual Vividness". The Journal of Neuroscience. 35 (16): 6506–6516. doi:10.1523/JNEUROSCI.4489-14.2015. PMC 6605217. PMID 25904801. ● Castillo, Stephanie (May 8, 2015). "The Highly Sensitive Person: Emotional Sensitivity May Stem From A Person's Genes, Enhancing The Way They See The World". Medical Daily (IBT Media). Archived from the original on May 11, 2015. ## External links[edit] * Bartz, Andrea (July 5, 2011). "Sense and Sensitivity". Psychology Today. Archived from the original on April 19, 2013. * Madrigal, Alix (July 28, 1999). "She Writes About a Touchy Subject / Book aims to help sensitive people". San Francisco Chronicle. Archived from the original on August 22, 2016. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Sensory processing sensitivity

None

wikipedia

https://en.wikipedia.org/wiki/Sensory_processing_sensitivity

{"wikidata": ["Q16261057"]}

A number sign (#) is used with this entry because of evidence that vitiligo-associated multiple autoimmune disease susceptibility mapping to chromosome 17p13 can be accounted for by variants in the NALP1 gene (NLRP1; 606636), which encodes NACHT leucine-rich repeat protein-1, a regulator of the innate immune system. Description Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. It is a genetically complex disorder involving multiple susceptibility genes and unknown environmental triggers. Patients with generalized vitiligo have elevated frequencies of other autoimmune diseases, suggesting that these diseases involve shared genetic components (summary by Jin et al., 2010). ### Genetic Heterogeneity of Vitiligo-Associated Multiple Autoimmune Disease Susceptibility Additional forms of vitiligo-associated multiple autoimmune disease susceptibility have been mapped to chromosomes 1p31 (VAMAS2, 607836, associated with mutation in the FOXD3 gene, 611539), 7 (VAMAS3; 608391), 8 (VAMAS4; 608392), 4 (VAMAS5; 609400), and 6p21.3 (VAMAS6; 193200). Clinical Features McKusick (1983) observed a family in Maine in which vitiligo occurred in many members. The occurrence of halo nevi (see 234300) as a striking feature of the proband and some others suggested that this is a manifestation of vitiligo. Thyrotoxicosis and pernicious anemia were also present in the family. The family came from a moderately inbred community and the parents of the proband were probably remotely related. Other Features Bader et al. (1975) reported an 8-year-old female with vitiligo and dysgammaglobulinemia characterized by absent IgA, very low IgG, and normal IgM. The T-cell immune system was intact but other family members had low levels or absence of IgA. Inheritance Lerner (1959) suggested autosomal dominant inheritance of vitiligo. In an inbred group in Louisiana, Thurmon et al. (1975) observed vitiligo in several sibships descendant through both parents from a common ancestor. Three sibs with vitiligo (onset at age 5 or 6 years) had congenital deafness. Vitiligo patterns on opposite sides of the body and in pairs of identical twins were generally similar. From 160 probands ascertained through the U.S. National Vitiligo Foundation, Majumder et al. (1993) confirmed the existence of a familial aggregation for vitiligo, i.e., 20% of probands reported 1 or more first-degree relatives also affected with this skin disorder. Offspring of probands were found to have the highest relative risk for developing vitiligo, followed by sibs, parents, and grandparents. In a separate paper based on the same data, Nath et al. (1994) cross-validated the genetic model proposed by Majumder et al., 1988 to explain the nonmendelian segregation of vitiligo. They postulated that 3 epistatically interacting autosomal diallelic loci are involved in the pathogenesis of vitiligo and that affected individuals are recessive homozygotes at each of the 3 loci. Mapping Both systemic lupus erythematosus (SLE; 152700) and vitiligo are autoimmune disorders that have strong evidence of complex genetic contributions to their etiology. Since autoimmune diseases are thought to share at least some of their genetic origins, and since only a small minority (16 of 92) of the European-American pedigrees multiplex for SLE in their collection had one or more affected members with vitiligo, Nath et al. (2001) hypothesized that these pedigrees might be more genetically homogeneous at loci important to be both SLE and vitiligo and, hence, have increased power for detection of linkage. In a genomewide screen of 16 European-American pedigrees, they identified a significant linkage at 17p13, where the maximum multipoint parametric lod score was 3.64 and the nonparametric linkage score was 4.02. The segregation behavior of this linkage suggested a recessive mode of inheritance with a virtually homogeneous genetic effect in these 16 pedigrees. The results supported the hypotheses that SLE and vitiligo may share important genetic effects and that sampling on the basis of clinical covariates dramatically improves the power to identify genetic effects. Spritz et al. (2004) confirmed the mapping of SLEV1 on chromosome 17 and identified 2 novel vitiligo susceptibility loci, 1 on chromosome 7 (AIS2; 608391) and 1 on chromosome 8 (AIS3; 608392). Using 350 microsatellite markers, Johansson et al. (2004) performed a genomewide scan in 20 Argentine families with SLE and found significant linkage to chromosome 17p12-q11, with a maximum lod score of 3.88 for marker D17S1294 in combination with D17S1293 under a dominant inheritance model. Jin et al. (2007) tested 177 SNPs spanning the 17p13 linkage peak for association with vitiligo-related multiple autoimmune disease spanning the 17p13 linkage peak and identified NALP1 (606636) as a strong candidate gene. They then sequenced DNA in and around the gene to identify additional SNPs. In a second round of tests of association, they demonstrated 2 variants that contribute independently to the risk of the disease. One was a nonsynonymous coding region change in the NAPL1 gene, leu155 to his (606636.0001); the second was an SNP in the promoter region of the gene. Jin et al. (2007) studied a series of 2 families, the first comprising the 51 extended families used by Spritz et al. (2004) to map the locus to 17p13, and a second comprising 63 similar independent families. Families had 2 or more individuals with generalized vitiligo and at least 1 having 1 or more of the autoimmune or autoinflammatory diseases epidemiologically associated with vitiligo, including autoimmune thyroid disease (see 140300, 275000), rheumatoid arthritis (180300), and systemic lupus erythematosus (152700). ### Associations Pending Confirmation In a genomewide association study of 1,392 unrelated patients of European origin, followed by replication a case-control cohort of 677 patients and 1,106 controls and a family-based cohort of 183 simplex trios and 332 multiplex families, Jin et al. (2010) found an association with 1393350 in the TYR gene (606933) on chromosome 11q14.3 (combined p = 1.60 x 10(-18); OR, 1.53). Further analysis showed epistasis between TYR and HLA-A, consistent with the observation that tyrosinase is presented by HLA-A*0201. Jin et al. (2010) identified 10 confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genomewide study, using 2 replication cohorts of European descent (one comparing 647 unrelated individuals with generalized vitiligo and 1,056 controls and the second consisting of 183 simplex generalized vitiligo trios and 332 generalized vitiligo multiplex families), Jin et al. (2010) observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (605515) (rs17008723, combined P = 1.04 x 10(-8); OR = 1.33) and with variants at 6q27 encompassing the CCR6 gene (601835) (rs6902119, combined P = 3.94 x 10(-7); OR = 1.23). In a genomewide association study of generalized vitiligo in a Chinese Han population, Quan et al. (2010) identified a theretofore undescribed risk locus at 6q27 (rs2236313, combined P = 9.72 x 10(-17), OR = 1.20), which contains 3 genes: RNASET2 (612944), FGFR1OP (605392), and CCR6. The initial study consisted of 1,117 cases and 1,429 controls; the 34 most promising SNPs were replicated in 5,910 cases and 9,916 controls of Chinese Han origin and 713 cases and 824 controls of Chinese Uygur origin. History Goudie et al. (1980) suggested the existence of a 'genetically determined clonally based positioning system' modified during somatic growth. They considered the vitiligo mutation to be unstable and liable to further mutation. Majumder et al. (1988) suggested a multiple recessive homozygous model, i.e., that a set of 4 unlinked diallelic loci is involved in the causation of vitiligo. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

VITILIGO-ASSOCIATED MULTIPLE AUTOIMMUNE DISEASE SUSCEPTIBILITY 1

c1847835

omim

https://www.omim.org/entry/606579

{"omim": ["606579"], "synonyms": ["Alternative titles", "VITILIGO", "SYSTEMIC LUPUS ERYTHEMATOSUS, VITILIGO-RELATED"]}

Nutrient deficiency A young cabbage plant exhibiting nitrogen deficiency. All plants require sufficient supplies of macronutrients for healthy growth, and nitrogen (N) is a nutrient that is commonly in limited supply. Nitrogen deficiency in plants can occur when organic matter with high carbon content, such as sawdust, is added to soil.[1] Soil organisms use any nitrogen to break down carbon sources, making N unavailable to plants.[1] This is known as "robbing" the soil of nitrogen. All vegetables apart from nitrogen fixing legumes are prone to this disorder. Nitrogen deficiency can be prevented in the short term by using grass mowings as a mulch, or foliar feeding with manure, and in the longer term by building up levels of organic matter in the soil. Sowing green manure crops such as grazing rye to cover soil over the winter will help to prevent nitrogen leaching, while leguminous green manures such as winter tares will fix additional nitrogen from the atmosphere. ## Contents * 1 Symptoms * 1.1 Disease * 1.2 Effect on Potato Production * 2 Detection * 3 Corrective Measures * 4 See also * 5 References ## Symptoms[edit] Some symptoms of nitrogen deficiency (in absence or low supply) are given below : 1. The chlorophyll content of the plant leaves is reduced which results in pale yellow color (chlorosis). Older leaves turn completely yellow. 2. Flowering, fruitings, protein and starch contents are reduced. Reduction in protein results in stunted growth and dormant lateral buds.[2] ### Disease[edit] Plants look thin, pale and the condition is called general starvation.[2] ### Effect on Potato Production[edit] Symptoms of nitrogen deficiencies in plants is general chlorosis of the leaves, which is when leaves turn pale green, and leaves cup upwards quite severely in deficient plants.[3] Nitrogen deficiencies also cause leaves to remain small, and drop prematurely, resulting in less photosynthesis occurring in the plant, and fewer, smaller tubers can form for harvest. Research done by Yara International has shown that there is a direct correlation between tuber size and yield, and the amount of plant-available nitrogen in the soil. This makes it crucial that the fields have enough nitrogen in the soil to grow a prosperous crop.[4] However, excess nitrogen in the soil can also be harmful to potato production, influencing how well the roots are able to develop, and delays can occur in tuber initiation during the tuberization stage of potato growth.[5] ## Detection[edit] The visual symptoms of nitrogen deficiency mean that it can be relatively easy to detect in some plant species. Symptoms include poor plant growth, and leaves become pale green or yellow because they are unable to make sufficient chlorophyll. Leaves in this state are said to be chlorotic. Lower leaves (older leaves) show symptoms first, since the plant will move nitrogen from older tissues to more important younger ones.[6] Nevertheless, plants are reported to show nitrogen deficiency symptoms at different parts. For example, Nitrogen deficiency of tea is identified by retarded shoot growth and yellowing of younger leaves.[7] However, these physical symptoms can also be caused by numerous other stresses, such as deficiencies in other nutrients, toxicity, herbicide injury, disease, insect damage or environmental conditions. Therefore, nitrogen deficiency is most reliably detected by conducting quantitative tests in addition to assessing the plants visual symptoms. These tests include soil tests and plant tissue test.[8] Plant tissue tests destructively sample the plant of interest. However, nitrogen deficiency can also be detected non-destructively by measuring chlorophyll content. Chlorophyll content tests work because leaf nitrogen content and chlorophyll concentration are closely linked, which would be expected since the majority of leaf nitrogen is contained in chlorophyll molecules.[9] Chlorophyll content can be detected with a Chlorophyll content meter; a portable instrument that measures the greenness of leaves to estimate their relative chlorophyll concentration. Chlorophyll content can also be assessed with a chlorophyll fluorometer, which measures a chlorophyll fluorescence ratio to identify phenolic compounds that are produced in higher quantities when nitrogen is limited. These instruments can therefore be used to non-destructively test for nitrogen deficiency. ## Corrective Measures[edit] Fertilizers like ammonium phosphate, calcium ammonium nitrate, urea can be supplied. Foliar spray of urea can be a quick method.[2] ## See also[edit] * Nitrogen fixation * Protein deficiency ## References[edit] 1. ^ a b "Compost Fundamentals: Compost Needs - Carbon Nitrogen Relationships". 2. ^ a b c Pandey, S N; Sinha, B K (November 2009). "Mineral Nutrition". Plant Physiology (fourth ed.). 576Masjid Road, Jangpura, New Delhi-110014: VIKAS PUBLISHING HOUSE Pvt. Ltd. pp. 125–126. ISBN 978-8125918790.CS1 maint: location (link) 3. ^ "Idaho Nutrient Management - Potato". www.extension.uidaho.edu. Retrieved 2016-12-02. 4. ^ "Role of Nitrogen in Potato Production | N Deficiencies & Application | Yara". www.yara.us. Archived from the original on 2017-12-14. Retrieved 2016-12-02. 5. ^ Network, University of Nebraska-Lincoln | Web Developer (2015-09-17). "Nitrogen | CropWatch". cropwatch.unl.edu. Retrieved 2016-12-02. 6. ^ http://www.rainbowplantfood.com/agronomics/efu/nitrogen.pdf 7. ^ "Soil & Nutrition | Upasi Tea Research Foundation (TRF)". 8. ^ "CROP NUTRIENT DEFICIENCIES - TOXICITIES | Plant Nutrition | Nutrients". 9. ^ http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=2349&context=extensionhist * v * t * e Plant nutrition / Fertilizer Imbalances * Boron deficiency * Calcium deficiency * Iron deficiency * Magnesium deficiency#Plants * Manganese deficiency * Molybdenum deficiency * Nitrogen deficiency * Phosphorus deficiency * Potassium deficiency * Zinc deficiency * Micronutrient deficiency * Chlorosis * Fertilizer burn Assimilation * Nitrogen assimilation * Phosphorus assimilation * Sulfur assimilation * Microbial assistance * Photorespiration Methods * Fertigation * Fertilizer tree * Green manure * Hoagland solution * Hydroponic dosers * Living mulch * Nutrient budgeting * Nutrient management * Organic fertilizer * Plant tissue test Miscellaneous * Soil fertility * Nutrient pollution * Soil pH * Agrobiology Related concepts * Algal nutrient solutions *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Nitrogen deficiency

None

wikipedia

https://en.wikipedia.org/wiki/Nitrogen_deficiency

{"wikidata": ["Q923534"]}

This article is about calluses and corns of human skin. For other uses, see Callus (disambiguation). This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Callus" – news · newspapers · books · scholar · JSTOR (January 2010) (Learn how and when to remove this template message) This article is missing information about evolution and biology. Please expand the article to include this information. Further details may exist on the talk page. (July 2019) (Learn how and when to remove this template message) Thickened and hardened area of skin Callus Examples of callus found on the toe SpecialtyDermatology ComplicationsSkin ulceration, infection Calluses (plantar in left foot and lateral in right foot) A callus is an area of thickened skin that forms as a response to repeated friction, pressure, or other irritation. Since repeated contact is required, calluses are most often found on the feet and hands, but they may occur anywhere on the skin. Some degree of callus, such as on the bottom of the foot, is normal.[1] Calluses are generally not harmful and help prevent blisters, as well as offering protection.[2] However, excessive formation may sometimes lead to other problems, such as a skin ulceration or infection, or cause the sufferer to try to offload the affected painful area, which can place excessive stress on the asymptomatic side. Rubbing that is too frequent or forceful will cause blisters, as opposed to calluses, to form. ## Contents * 1 Cause * 1.1 Corns * 2 Prevention * 3 Treatment * 3.1 Diabetes * 4 See also * 5 Notes * 6 References * 7 External links ## Cause[edit] Normally, a callus will form on any part of the skin exposed to excess friction over a long period of time. For example, people often develop calluses on the middle finger or ring finger of their dominant hand due to writing with a pen or pencil. Another cause is from playing string instruments like the guitar or the violin; calluses will develop on the four fingers of the hand used in holding the strings down to the fingerboard, and sometimes on the fingers of the hand used for pizzicato or strumming. Weightlifters commonly experience callus on the upper-palm area due to repeated friction. Calluses are also very common on the fingers of rock climbers on almost all of their fingers. There are many activities that can result in the formation of a callus, which may even be viewed as a badge of experience and commitment to the activity. Activities that are known for causing calluses include (but are not limited to) construction work, many sports, wood carving, playing musical instruments, use of a chef's knife, rock climbing, hiking, martial arts, weight training, rowing, BMXing, dancing (especially ballet), chopping wood, monkey bars and wearing high heels. Tenpin bowlers will often develop calluses on their thumbs and occasionally their middle fingers from frequent bowling. Calluses have also been known to develop on the forehead from the frequent prostrations required in Muslim prayer; known as a prayer bump or zebiba, such calluses are considered marks of piety in some Muslim countries, and people have been known to take special steps, such as praying on straw mats, to encourage the callus to develop.[3] Although calluses can occur anywhere on the body as a reaction to moderate, constant "grinding" pressure, they are most often found on the foot (where the most pressure and friction are applied). On the feet, arguably the source of the most problematic calluses, they typically form on the metatarsal-phalangeal joint area ("balls of the foot"), heels and small toes due to the compression applied by tightly fitting shoes. Biologically, calluses are formed by the accumulation of terminally differentiated keratinocytes in the outermost layer of skin. Though the cells of calluses are dead, they are quite resistant to mechanical and chemical insults due to extensive networks of cross-linked proteins and hydrophobic keratin intermediate filaments containing many disulfide bonds.[4] It is the natural reaction of the palmar or plantar skin. Too much friction occurring too fast for the skin to develop a protective callus will cause a blister or abrasion instead. Sometimes a callus occurs where there is no rubbing or pressure. These hyperkeratoses can have a variety of causes. Some toxic materials, such as arsenic, can cause thick palms and soles. Some diseases, such as syphilis, can cause thickening of the palms and soles as well as pinpoint hyperkeratoses. There is a benign condition called keratosis palmaris et plantaris, which produces corns in the creases of the fingers and non-weight bearing spaces of the feet. Some of this may be caused by actinic keratosis, which occurs due to overexposure to sun or with age and hormonal shifts. ### Corns[edit] Main article: Corn (medicine) Painful corns A corn (or clavus, plural clavi) is a specially shaped callus of dead skin that usually occurs on thin or glabrous (hairless and smooth) skin surfaces, especially on the dorsal surface of toes or fingers. They can sometimes occur on the thicker palmar or plantar skin surfaces. Corns form when the pressure point against the skin traces an elliptical or semi-elliptical path during the rubbing motion, the center of which is at the point of pressure, gradually widening. If there is constant stimulation of the tissue producing the corns, even after the corn is surgically removed, the skin may continue to grow as a corn.[citation needed] The hard part at the center of the corn resembles a funnel with a broad raised top and a pointed bottom. Because of their shape, corns intensify the pressure at the tip and can cause deep tissue damage and ulceration.[5] The scientific name for a corn is heloma (plural helomata). A hard corn is called a heloma durum, while a soft corn is called a heloma molle. The location of the soft corns tends to differ from that of hard corns. Hard corns occur on dry, flat surfaces of skin. Soft corns (frequently found between adjacent toes) stay moist, keeping the surrounding skin soft. The corn's center is not soft however, but indurated. The specific diagnostic workup and treatments for corns may differ substantially from other forms of calluses. ## Prevention[edit] Corns and calluses are easier to prevent than to treat. When it is undesirable to form a callus, minimizing rubbing and pressure will prevent callus formation. Footwear should be properly fitted,[6] gloves may be worn, and protective pads, rings or skin dressings may be used. People with poor circulation or sensation should check their skin often for signs of rubbing and irritation so they can minimize any damage. ## Treatment[edit] A person with callus at the barber surgeon's, 17th century Calluses and corns may heal by themselves eventually, once the irritation is consistently avoided. They may also be dissolved with keratolytic agents containing salicylic acid, sanded down with a pumice stone or silicon carbide sandpaper or filed down with a callus shaver, or pared down by a professional such as a podiatrist.[7] ### Diabetes[edit] People with diabetes face special skin challenges. Because diabetes affects the capillaries, the small blood vessels which feed the skin, thickening of the skin with callus increases the difficulty of supplying nutrients to the skin.[citation needed] Callus formation is seen in high numbers of patients with diabetes, and together with absent foot pulses and formation of hammer toe,[8][9] this may be an early sign of individuals at an increased risk for foot ulcers.[8] The stiffness of a callus or corn, coupled with the shear and pressure that caused it, may tear the capillaries or adjoining tissue, causing bleeding within the callus or corn. Often, bleeding within a callus is an early sign of diabetes, even before elevated blood sugars may be noticed. Although the bleeding can be small, sometimes small pools of blood or hematoma are formed. The blood itself is an irritant, a foreign body within the callus that makes the area burn or itch. If the pool of blood is exposed to the outside, infection may follow. Infection may also lead to ulceration. This process can be prevented at several places. Diabetic foot infections are the leading cause of diabetic limb amputation. ## See also[edit] * Hyperkeratosis * Callosity * Catagmatic ## Notes[edit] 1. ^ Corns and Calluses, Cleveland Clinic 2. ^ Are Calluses Actually Bad for Your Feet? See What Podiatrists Have to Say, Footwear News 3. ^ Slackman, Michael (December 18, 2007). "Fashion and Faith Meet, on Foreheads of the Pious". New York Times. Retrieved 2018-08-08. 4. ^ Tantisiriwat N, Janchai S (Dec 1991). "Transglutaminases: multifunctional cross-linking enzymes that stabilize tissues". The FASEB Journal. 5 (15): 3071–7. PMID 1683845. 5. ^ eMedicine > Clavus By Nanette Silverberg. Updated: Apr 9, 2010 6. ^ Erstad, Shannon (6 March 2008). "Foot problems: Finding the right shoes". WebMD Medical Reference from Healthwise. Healthwise. "How do I find the right shoes?". Retrieved 2010-06-10. "You should not have to "break in" shoes if they fit properly." 7. ^ Corns and calluses: Treatments and drugs. Mayo Clinic. Retrieved July 23, 2009. 8. ^ a b Alavi A, Sanjari M, Haghdoost A, Sibbald RG (April 2009). "Common foot examination features of 247 Iranian patients with diabetes". Int Wound J. 6 (2): 117–22. doi:10.1111/j.1742-481X.2009.00583.x. PMID 19432661. -12% having callus formation 9. ^ Tantisiriwat N, Janchai S (July 2008). "Common foot problems in diabetic foot clinic". J Med Assoc Thai. 91 (7): 1097–101. PMID 18839852. -56% having callus present ## References[edit] * Taber's Cyclopedic Medical Dictionary, 15th Edition, CL Thomas, M.D., M.P.H., editor, F.A. Davis Company, Philadelphia, PA, 1985. * The Merck Manual of Medical Information, Home Edition, R Berkow, M.D., et al., editors, Merck Research Laboratories, Whitehouse Station, NJ, 1997. ## External links[edit] Classification D * ICD-10: L84 * ICD-9-CM: 700 * MeSH: D002145 This article is about callous. For a definition of the word "callus", see the Wiktionary entry callus. * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Cutaneous keratosis, ulcer, atrophy, and necrobiosis Epidermal thickening * keratoderma: Keratoderma climactericum * Paraneoplastic keratoderma * Acrokeratosis paraneoplastica of Bazex * Aquagenic keratoderma * Drug-induced keratoderma * psoriasis * Keratoderma blennorrhagicum * keratosis: Seborrheic keratosis * Clonal seborrheic keratosis * Common seborrheic keratosis * Irritated seborrheic keratosis * Seborrheic keratosis with squamous atypia * Reticulated seborrheic keratosis * Dermatosis papulosa nigra * Keratosis punctata of the palmar creases * other hyperkeratosis: Acanthosis nigricans * Confluent and reticulated papillomatosis * Callus * Ichthyosis acquisita * Arsenical keratosis * Chronic scar keratosis * Hyperkeratosis lenticularis perstans * Hydrocarbon keratosis * Hyperkeratosis of the nipple and areola * Inverted follicular keratosis * Lichenoid keratosis * Multiple minute digitate hyperkeratosis * PUVA keratosis * Reactional keratosis * Stucco keratosis * Thermal keratosis * Viral keratosis * Warty dyskeratoma * Waxy keratosis of childhood * other hypertrophy: Keloid * Hypertrophic scar * Cutis verticis gyrata Necrobiosis/granuloma Necrobiotic/palisading * Granuloma annulare * Perforating * Generalized * Subcutaneous * Granuloma annulare in HIV disease * Localized granuloma annulare * Patch-type granuloma annulare * Necrobiosis lipoidica * Annular elastolytic giant-cell granuloma * Granuloma multiforme * Necrobiotic xanthogranuloma * Palisaded neutrophilic and granulomatous dermatitis * Rheumatoid nodulosis * Interstitial granulomatous dermatitis/Interstitial granulomatous drug reaction Foreign body granuloma * Beryllium granuloma * Mercury granuloma * Silica granuloma * Silicone granuloma * Zirconium granuloma * Soot tattoo * Tattoo * Carbon stain Other/ungrouped * eosinophilic dermatosis * Granuloma faciale Dermis/ localized CTD Cutaneous lupus erythematosus * chronic: Discoid * Panniculitis * subacute: Neonatal * ungrouped: Chilblain * Lupus erythematosus–lichen planus overlap syndrome * Tumid * Verrucous * Rowell's syndrome Scleroderma/ Morphea * Localized scleroderma * Localized morphea * Morphea–lichen sclerosus et atrophicus overlap * Generalized morphea * Atrophoderma of Pasini and Pierini * Pansclerotic morphea * Morphea profunda * Linear scleroderma Atrophic/ atrophoderma * Lichen sclerosus * Anetoderma * Schweninger–Buzzi anetoderma * Jadassohn–Pellizzari anetoderma * Atrophoderma of Pasini and Pierini * Acrodermatitis chronica atrophicans * Semicircular lipoatrophy * Follicular atrophoderma * Linear atrophoderma of Moulin Perforating * Kyrle disease * Reactive perforating collagenosis * Elastosis perforans serpiginosa * Perforating folliculitis * Acquired perforating dermatosis Skin ulcer * Pyoderma gangrenosum Other * Calcinosis cutis * Sclerodactyly * Poikiloderma vasculare atrophicans * Ainhum/Pseudo-ainhum *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Callus

c0376154

wikipedia

https://en.wikipedia.org/wiki/Callus

{"mesh": ["D002145"], "icd-9": ["700"], "icd-10": ["L84"], "wikidata": ["Q2197452"]}

Cholera is an infection of the small intestines that is caused by the bacterium Vibrio cholera. The condition can range from mild to severe and many affected people may have no obvious signs or symptoms. Approximately 5-10% of infected people will have severe disease with watery diarrhea and vomiting leading to rapid fluid loss, dehydration, and shock. If left untreated, this can cause acute renal failure, severe electrolyte imbalances, coma, or even death. People develop cholera when they eat food or drink water that is contaminated with Vibrio cholera. The condition occurs most often in places that lack water treatment and have poor sanitation and inadequate hygiene. Treatment aims to prevent dehydration and replace the fluids and salts that are lost through diarrhea. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Cholera

c0008354

gard

https://rarediseases.info.nih.gov/diseases/6043/cholera

{"mesh": ["D002771"], "umls": ["C0008354"], "orphanet": ["173"], "synonyms": ["Vibrio cholerae infection"]}

Pityriasis alba SpecialtyDermatology Pityriasis alba is a skin condition, a type of dermatitis,[1] commonly seen in children and young adults as dry, fine-scaled, pale patches on the face. It is self-limiting and usually only requires use of moisturizer creams.[2] The condition is so named for the fine scaly appearance initially present (pityriasis), and alba (Latin for white) refers to the pallor of the patches that develop. The patches are not totally depigmented.[3] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Differential diagnosis * 5 Treatment * 6 Prognosis * 7 Epidemiology * 8 History * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] The dry scaling appearance is most noticeable during the winter as a result of dry air inside people's homes.[1] During the summer, tanning of the surrounding normal skin makes the pale patches of pityriasis alba more prominent.[1] Individual lesions develop through 3 stages and sometimes are itchy: 1. Raised and red – although the redness is often mild and not noticed by parents 2. Raised and pale 3. Smooth flat pale patches[1] Lesions are round or oval raised or flat, of 0.5–2 cm in size although may be larger if they occur on the body (up to 4 cm), and usually number from 4 or 5 to over 20. The patches are dry with very fine scales. They most commonly occur on the face (cheeks), but in 20% appear also on the upper arms, neck, or shoulders.[1][2] The diagnostic differential should consider tinea and vitiligo amongst other causative factors.[4] ## Cause[edit] Any dermatitis may heal leaving pale skin, as may excessive use of corticosteroid creams used to treat episodes of eczema. The hypopigmentation is due to both reduced activity of melanocytes with fewer and smaller melanosomes.[5][6] The cause of pityriasis alba is not known. Dry skin and atopic dermatitis may co-exist. The patches may become more apparent after sun exposure, when the normal surrounding skin is tanned.[1] The role of ultraviolet radiation, bathing or not bathing, low serum copper and Malassezia yeasts is not clear.[1] ## Diagnosis[edit] Diagnosis is mainly done by clinical examination. Shining a Wood's light over the skin may reveal further lesions not obviously visible otherwise.[2] ## Differential diagnosis[edit] * Pytriasis versicolor and leprosy.[citation needed] ## Treatment[edit] No treatment is required and the patches in time will settle.[7] The redness, scale and itch if present may be managed with simple emollients and sometimes hydrocortisone, a weak steroid, is also used.[8] As the patches of pityriasis alba do not darken normally in sunlight, effective sun protection helps minimise the discrepancy in colouration against the surrounding normal skin. Cosmetic camouflage may be required. Tacrolimus has been reported as speeding resolution.[9] In exceptionally severe cases PUVA therapy may be considered.[10] ## Prognosis[edit] The patches of pityriasis alba may last from 1 month to about one year, but commonly on the face last a year. However it is possible that the white patches may last for more than 1 year on the face. ## Epidemiology[edit] It occurs in mainly children and adolescents of all races, particularly people with dark skin. The worldwide prevalence is 5% in children, with boys and girls affected equally.[1] adults can also suffer from this disease.[11] Up to a third of US school children may at some stage have this condition. Single-point prevalence studies from India have shown variable rates from 8.4%[12] to 31%.[13] Other studies have shown prevalence rates in Brazil of 9.9%,[14] Egypt 13.49%,[15] Romania 5.1%,[16] Turkey 12% where higher rates were seen in those with poor socioeconomic conditions,[17] and just 1% in school children in Hong Kong.[18] In 1963, one school health clinic reported features of pityriasis alba in two fifths of their children.[2] ## History[edit] It was first described in 1923. Having been known under a variety of names, the term 'Pityriasis alba', coined in 1956, has stayed.[2][19] ## See also[edit] * Leprosy * List of cutaneous conditions * Vitiligo which, by comparison, causes total loss of skin colour or on the face and tends to occur around the mouth and eyes.[3] ## References[edit] 1. ^ a b c d e f g h "Pityriasis alba | DermNet NZ". dermnetnz.org. Retrieved 12 March 2020. 2. ^ a b c d e Nordlund, James J.; Boissy, Raymond E.; Hearing, Vincent J.; King, Richard A.; Oetting, William S.; Ortonne, Jean-Paul (2008). The Pigmentary System: Physiology and Pathophysiology. John Wiley & Sons. ISBN 978-1-4051-5733-9. 3. ^ a b Pinto FJ, Bolognia JL (1991). "Disorders of hypopigmentation in children". Pediatric Clinics of North America. 38 (4): 991–1017. doi:10.1016/S0031-3955(16)38164-0. PMID 1870914. 4. ^ Pityriasis Alba at eMedicine 5. ^ Vargas-Ocampo F (1993). "Pityriasis alba: a histologic study". Int. J. Dermatol. 32 (12): 870–873. doi:10.1111/j.1365-4362.1993.tb01401.x. PMID 8125687. 6. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. 7. ^ Lin RL, Janniger CK (2005). "Pityriasis alba". Cutis; Cutaneous Medicine for the Practitioner. 76 (1): 21–4. PMID 16144284. 8. ^ Harper J (1988). "Topical corticosteroids for skin disorders in infants and children". Drugs. 36 Suppl 5: 34–7. doi:10.2165/00003495-198800365-00007. PMID 2978289. 9. ^ Rigopoulos D, Gregoriou S, Charissi C, Kontochristopoulos G, Kalogeromitros D, Georgala S (2006). "Tacrolimus ointment 0.1% in pityriasis alba: an open-label, randomized, placebo-controlled study". Br. J. Dermatol. 155 (1): 152–155. doi:10.1111/j.1365-2133.2006.07181.x. PMID 16792767. 10. ^ Di Lernia V, Ricci C (2005). "Progressive and extensive hypomelanosis and extensive pityriasis alba: same disease, different names?". Journal of the European Academy of Dermatology and Venereology : JEADV. 19 (3): 370–372. doi:10.1111/j.1468-3083.2004.01170.x. PMID 15857470. 11. ^ Blessmann Weber M, Sponchiado de Avila LG, Albaneze R, Magalhães de Oliveira OL, Sudhaus BD, Cestari TF (2002). "Pityriasis alba: a study of pathogenic factors". Journal of the European Academy of Dermatology and Venereology : JEADV. 16 (5): 463–468. doi:10.1046/j.1468-3083.2002.00494.x. PMID 12428838. 12. ^ Dogra S, Kumar B (2003). "Epidemiology of skin diseases in school children: a study from northern India". Pediatric Dermatology. 20 (6): 470–473. doi:10.1111/j.1525-1470.2003.20602.x. PMID 14651562. 13. ^ Faye O, N'Diaye HT, Keita S, Traoré AK, Hay RJ, Mahé A (2005). "High prevalence of non-leprotic hypochromic patches among children in a rural area of Mali, West Africa". Leprosy Review. 76 (2): 144–6. PMID 16038247. 14. ^ Bechelli LM, Haddad N, Pimenta WP, Pagnano PM, Melchior E, Fregnan RC, Zanin LC, Arenas A (1981). "Epidemiological survey of skin diseases in schoolchildren living in the Purus Valley (Acre State, Amazonia, Brazil)". Dermatologica. 163 (1): 78–93. doi:10.1159/000250144. PMID 7274519. 15. ^ Abdel-Hafez K, Abdel-Aty MA, Hofny ER (2003). "Prevalence of skin diseases in rural areas of Assiut Governorate, Upper Egypt". Int. J. Dermatol. 42 (11): 887–892. doi:10.1046/j.1365-4362.2003.01936.x. PMID 14636205. 16. ^ Popescu R, Popescu CM, Williams HC, Forsea D (1999). "The prevalence of skin conditions in Romanian school children". Br. J. Dermatol. 140 (5): 891–896. doi:10.1046/j.1365-2133.1999.02821.x. PMID 10354028. 17. ^ Inanir I, Sahin MT, Gündüz K, Dinç G, Türel A, Oztürkcan S (2002). "Prevalence of skin conditions in primary school children in Turkey: differences based on socioeconomic factors". Pediatric Dermatology. 19 (4): 307–311. doi:10.1046/j.1525-1470.2002.00087.x. PMID 12220273. 18. ^ Fung WK, Lo KK (2000). "Prevalence of skin disease among school children and adolescents in a Student Health Service Center in Hong Kong". Pediatric Dermatology. 17 (6): 440–446. doi:10.1046/j.1525-1470.2000.01841.x. PMID 11123774. 19. ^ O'farrell, Norman M. (1 April 1956). "Pityriasis Alba". A.M.A. Archives of Dermatology. 73 (4): 376–377. doi:10.1001/archderm.1956.01550040070010. ISSN 0096-5359. ## External links[edit] Classification D * ICD-10: L30.5 (ILDS L30.590) * ICD-9-CM: 696.5 * DiseasesDB: 31121 External resources * MedlinePlus: 001463 * eMedicine: ped/1813 derm/333 emerg/425 * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Pityriasis alba

c0085657

wikipedia

https://en.wikipedia.org/wiki/Pityriasis_alba

{"umls": ["C0085657"], "icd-9": ["696.5"], "icd-10": ["L30.5"], "wikidata": ["Q766511"]}

A rare non-syndromic syndactyly characterized by unilateral or bilateral fusion of the 4th and 5th metacarpals with no other associated abnormalities. Patients present shortened 4th and 5th metacarpals with excessive separation between their distal ends, resulting in marked ulnar deviation of the little finger and an inability to bring the 5th finger in parallel with the other fingers. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Syndactyly type 8

c1839728

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2498

{"gard": ["3559"], "mesh": ["C564100"], "omim": ["309630"], "umls": ["C1839728"], "icd-10": ["Q70.0"], "synonyms": ["Fusion of metacarpals 4 and 5"]}

## Prevalence[edit] Madagascar is among very few countries in Sub-Saharan Africa with an opportunity to slow the human immunodeficiency virus epidemic and avert the socioeconomic destruction that is evident in high-prevalence areas. With the internal and external migration of workforce to keep up with the labor needs of these economic zones, Madagascar will be faced with an increased problem containing HIV, which would have a negative effect on the economic and development efforts. If these problems are not proactively addressed, Madagascar could actually reverse the benefits brought to the country through the period of economic prosperity and increase its health and social burden.[1] Even though low, the HIV prevalence in Madagascar is increasing, as seen among pregnant women attending antenatal clinics; prevalence in this population rose from 0.064% in 1995 to 1.1% in 2003. Madagascar's rapid increase in HIV prevalence is likely influenced by a variety of conditions, including low literacy, widespread poverty, limited access to health and social services, high rates of partner change, and an increasingly transient population. Madagascar also has some of the highest rates of sexually transmitted infections (STIs) in the world. Services for prevention and treatment of HIV, such as counseling and testing and antiretroviral therapy, are being offered, but only a small portion of the Malagasy in need currently benefit from these interventions. At the end of 2003, Madagascar had only 13 sites offering counseling and testing services to 2,082 clients annually. Treatment for HIV is still limited in Madagascar, with only one site in the country currently offering antiretroviral therapy at the end of 2003. As of September 2004, only 30 of an estimated 17,000 adults in need of treatment for advanced HIV were receiving antiretroviral therapy.[1] ## National response[edit] Efforts by the United States Agency for International Development (USAID) and other donors to garner the commitment of the Government of Madagascar to HIV prevention and treatment have paid off. One of the primary supports to addressing Madagascar's emerging epidemic is the powerful political commitment at the highest levels of the new government. Just after his inauguration in 2002, President Marc Ravalomanana publicly established his leadership in HIV prevention. He chairs the nation's multisectoral HIV/AIDS program [Conseil National de Lutte contre le SIDA (CNLS)]. President Ravalomanana is committed to aggressively fighting the spread of HIV, and the government has taken bold steps to control the spread of the infection. The National Strategic Framework was approved by the government in December 2001 and was adjusted following the first national seroprevalence survey in 2003. The country's overall strategy focuses on behavior change and prevention, treatment of HIV and STIs, and AIDS education.[1] With the guidance of USAID and other partners, the Government of Madagascar is actively responding to gaps in its HIV/AIDS program. The government will use $13.4 million from The Global Fund to Fight AIDS, Tuberculosis and Malaria to expand current interventions by opening 40 new counseling and testing sites in 2005 and will reinforce existing HIV-prevention measures by ensuring use of universal precaution measures, reinforcing blood transfusion safety, and providing free condoms in public health care facilities. New interventions will include measures to prevent mother-to-child HIV transmission in 11 districts and the provision of psychosocial and community medical care for about 500 to 750 persons living with HIV/AIDS. The program will also lay the groundwork for the care of the estimated 30,000 children orphaned by AIDS.[1] ## References[edit] 1. ^ a b c d "Health Profile: Madagascar" Archived 2008-08-16 at the Wayback Machine. USAID (February 2005). This article incorporates text from this source, which is in the public domain. * v * t * e HIV/AIDS in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * Mayotte / Réunion (France) * Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom) * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and HIV/AIDS Social * AIDS orphan * Catholic Church and HIV/AIDS * Circumcision and HIV * Criminal transmission * Discrimination against people * Economic impact * Cost of treatment * HIV-affected community * HIV/AIDS activism * HIV/AIDS denialism * Red ribbon * Safe sex * Sex education * List of HIV-positive people * People With AIDS Self-Empowerment Movement * HIV/AIDS in the porn industry Culture * Discredited HIV/AIDS origins theories * International AIDS Conference * International AIDS Society * Joint United Nations Programme on HIV/AIDS (UNAIDS) * Media portrayal of HIV/AIDS * Misconceptions about HIV/AIDS * President's Emergency Plan for AIDS Relief (PEPFAR) * The SING Campaign * Solidays * Treatment Action Campaign * World AIDS Day * YAA/Youthforce * "Free Me" * Larry Kramer * Gay Men's Health Crisis * ACT UP * Silence=Death Project HIV/AIDS pandemic by region / country Africa * Angola * Benin * Botswana * Democratic Republic of the Congo * Egypt * Eswatini * Ethiopia * Ghana * Guinea * Côte d'Ivoire (Ivory Coast) * Kenya * Lesotho * Madagascar * Malawi * Mali * Mozambique * Namibia * Niger * Nigeria * Rwanda * Senegal * Tanzania * South Africa * Uganda * Zambia * Zimbabwe North America * Canada * Mexico * El Salvador * Guatemala * Honduras * Nicaragua United States * New York City Caribbean * Haiti * Jamaica * Dominican Republic South America * Bolivia * Brazil * Colombia * Guyana * Peru Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Cambodia * China (PRC) (Yunnan) * East Timor * India * Indonesia * Iran * Iraq * Japan * Jordan * North Korea * Laos * Malaysia * Myanmar (Burma) * Nepal * Pakistan * Philippines * Saudi Arabia * Sri Lanka * Taiwan (ROC) * Thailand * United Arab Emirates * Turkey * Vietnam Europe * United Kingdom * Russia * Ukraine Oceania * Australia * New Zealand * Papua New Guinea * List of countries by HIV/AIDS adult prevalence rate * List of HIV/AIDS cases and deaths registered by region *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

HIV/AIDS in Madagascar

None

wikipedia

https://en.wikipedia.org/wiki/HIV/AIDS_in_Madagascar

{"wikidata": ["Q5629858"]}

A rare chromosomal anomaly characterized by a combination of paternal uniparental and biparental cell lineages, leading to variable clinical presentation that predominantly includes features of Beckwith-Wiedemann syndrome and increased risk of various tumors. In addition, features of Angelman syndrome and transient neonatal diabetes might be expected. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Mosaic genome-wide paternal uniparental disomy

None

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=329813

{"synonyms": ["Androgenetic/biparental mosaicism", "Genome-wide paternal uniparental disomy mosaicism", "Mosaic genome-wide paternal UPD"]}

A number sign (#) is used with this entry because of evidence that maturity-onset diabetes of the young type 3 (MODY3) is caused by mutation in the hepatocyte nuclear factor-1-alpha gene (142410), which maps to chromosome 12q24.2. MODY is a form of familial noninsulin-dependent diabetes mellitus (NIDDM; 125853) and is characterized by an early age of onset (childhood, adolescence, or young adulthood under 25 years) and autosomal dominant inheritance. For general information on MODY and on genetic heterogeneity in this disorder, see 606391. In their review of MODY, Fajans et al. (2001) stated that, not unexpectedly, the pathophysiologic mechanisms of MODY due to mutations in the HNF4A gene (MODY1) and MODY due to mutations in the HNF1A (MODY3) are very similar since HNF4-alpha regulates the expression of HNF1-alpha. Patients with mutations in these genes may present with a mild form of diabetes. Despite similarly mild elevations in fasting plasma glucose concentrations, patients with mutations in HNF4A or HNF1A have significantly higher plasma glucose concentrations 2 hours after glucose administration than do persons with glucokinase mutations. The hyperglycemia in patients with MODY1 and MODY3 tends to increase over time, resulting in the need for treatment with oral hypoglycemic drugs or insulin in may of these patients (30 to 40% require insulin). These forms of MODY are associated with a progressive decrease in insulin secretion. In most populations, mutations in the HNF1A gene are the most common cause of MODY. Patients with MODY1 or MODY3 may have the full spectrum of complications of diabetes. Microvascular complications, particularly those involving the retina or kidneys, are as common in these patients as in patients with type I or type II diabetes (matched according to the duration of diabetes and the degree of glycemic control) and are probably determined by the degree of glycemic control. Patients with MODY1 lose the glucose priming effect of mild hyperglycemia on insulin secretion. Both prediabetic and diabetic persons with mutations in the HNF4A gene secrete decreased amounts of insulin in response to glucose and in response to arginine and also have an impairment of glucagon secretion in response to arginine. Furthermore, a defect in the hypoglycemia-induced secretion of pancreatic polypeptide has been found in prediabetic and diabetic persons who have mutations in the gene for HNF4A. These findings suggested that a deficiency of HNF4A resulting from mutations in this gene may affect the function of the beta, alpha, and pancreatic polypeptide cells within pancreatic islets. Patients with mutations in HNF1A have decreased renal absorption of glucose (i.e., a low renal threshold for glucose) and glycosuria. A deficiency of HNF4A affects triglyceride and apolipoprotein biosynthesis and is associated with a 50% reduction in serum triglyceride concentrations and a 25% reduction in serum concentrations of apolipoproteins AII and CIII and Lp(a). Fajans et al. (2001) reported that mutations in the HNF1A gene have been identified in all racial and ethnic backgrounds, including European, Chinese, Japanese, African, and American Indian. Mutations in the HNF1A gene appear to be the most common cause of MODY among adults seen in diabetic clinics. Ellard (2000) stated that 65 different mutations in the TCF1 gene had been found to cause MODY3 in a total of 116 families worldwide. They noted that diagnostic and predictive genetic testing is possible for the majority of patients with MODY, opening new avenues for the classification, prediction, and perhaps eventually the prevention of diabetes in these families. Vaxillaire et al. (1995) studied linkage in 12 French MODY families in which diabetes was not genetically linked to previously identified MODY loci. By a genomewide segregation analysis of highly informative microsatellite markers, they localized the gene for a MODY susceptibility locus (MODY3) to 12q in 6 families. The locus in question was thought to lie within a 7-cM interval bracketed by D12S86 and D12S342 (in 12q22-qter). The patients exhibited major hyperglycemia with a severe insulin (176730) secretory defect, suggesting that the causal gene is implicated in pancreatic beta-cell function. Lesage et al. (1995) studied the possible implication of the MODY3 locus in late-onset NIDDM. In 600 affected sib pairs from 172 French families, linkage was rejected by all methods of analysis, implying that the MODY gene on 12q is not a major gene in late-onset NIDDM in this population. Menzel et al. (1995) found evidence of linkage to chromosome 12 in 3 families with MODY from Denmark, Germany, and the U.S. (Michigan) and suggestive evidence of linkage in a family from Japan. They placed the locus in a 5-cM interval between markers D12S86 and D12S807/D12S820. The age of onset of NIDDM was less than 25 years of age in the youngest generation in each pedigree and the segregation was consistent with autosomal dominant inheritance. In 1 pedigree, the body weight of 18 of 22 diabetic subjects was known and only 1 was obese. Diabetes was diagnosed in all but 1 of the subjects before 20 years of age. From the location of the linked markers the MODY3 locus was thought to be in the region 12q24.1-q24.32. Mahtani et al. (1996) screened over 4,000 individuals from a Swedish-speaking population isolate in western Finland and identified 26 families enriched for NIDDM. Families with the lowest insulin levels showed linkage to 12q24 near D12S1349. Unlike MODY3 families, the Finnish families with low insulin had an age of onset typical for NIDDM (mean = 58 years). Mahtani et al. (1996) inferred the existence of a gene, NIDDM2 (601407), causing noninsulin-dependent diabetes mellitus associated with low insulin secretion and suggested that NIDDM2 and MODY3 may represent different alleles of the same gene. Yamagata et al. (1996) refined the localization of the MODY3 gene by a combination of genetic mapping and fluorescence in situ hybridization which localized the gene to 12q24.2. Lehto et al. (1997) analyzed the phenotype of affected members in 4 large Finnish MODY3 kindreds showing linkage to 12q with a maximum lod score of 15. They found evidence of severe impairment in insulin secretion, which was present also in those normal glycemic family members who had inherited the MODY3 gene. In contrast to patients with NIDDM, MODY3 patients did not show any features of the insulin resistance syndrome. They could be discriminated from patients with insulin-dependent diabetes mellitus by lack of glutamic acid decarboxylase antibodies. Taken together with the finding of linkage between this region on chromosome 12 and an insulin-deficient form of NIDDM, designated NIDDM2, as demonstrated by Mahtani et al. (1996), the data suggested to Lehto et al. (1997) that mutations at the MODY3/NIDDM2 gene(s) result in a reduced insulin secretory response that subsequently progresses to diabetes, and underlines the importance of subphenotypic classification in studies of diabetes. MODY3 and NIDDM2 may be different alleles of the same gene; NIDDM2 has an average age of onset of 58 years. Aguilar-Salinas et al. (2001) investigated possible defects in the insulin sensitivity and the acute insulin response in a group of Mexican patients displaying early-onset NIDDM and evaluated the contribution of mutations in 3 of the genes linked to MODY. They studied 40 Mexican patients diagnosed between 20 and 40 years of age, in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to MODY was carried out by PCR-SSCP. Among this group they found 2 individuals carrying missense mutations in exon 4 of the HNF4A gene and 1 carrying a nonsense mutation in exon 7 of the HNF1A gene; 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. The authors concluded that a defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 years of age. Mutations in either the HNF1A or the HNF4A genes were present among the individuals who developed early-onset diabetes in their population. Barrio et al. (2002) estimated the prevalence of major MODY subtypes in Spanish MODY families and analyzed genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the GCK (138079), HNF1A, and HNF4A genes using PCR-SSCP and/or direct sequencing. Mutations in MODY genes were identified in 64% of the families. Four pedigrees (18%) harbored mutations in the HNF1A/MODY3 gene, including a previously unreported change. The age at diagnosis was prepubertal in MODY2 index patients and pubertal in MODY3 patients. Overt diabetes was rare in MODY2 and was invariably present in MODY3 index patients. Chronic complications of diabetes were absent in the MODY2 population and were present in more than 40% of all relatives of MODY3 patients. Clinical expression of MODY3 and MODY1 mutations was more severe, including the frequent development of chronic complications. Inheritance \- Autosomal dominant (12q22-qter) Misc \- Early age of onset (under 25 years) Lab \- Hyperglycemia \- Severe insulin secretory defect Metabolic \- Maturity-onset diabetes of the young (MODY) \- Noninsulin-dependent diabetes mellitus ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3

c0342276

omim

https://www.omim.org/entry/600496

{"doid": ["0111102"], "mesh": ["C562772"], "omim": ["600496"], "orphanet": ["552"], "synonyms": ["Alternative titles", "MODY, TYPE 3"], "genereviews": ["NBK500456"]}

Tourist experience of being overwhelmed by finally visiting Paris This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Paris syndrome" – news · newspapers · books · scholar · JSTOR (July 2017) (Learn how and when to remove this template message) The Eiffel Tower in Paris Paris syndrome (French: syndrome de Paris, Japanese: パリ症候群, pari shōkōgun) is a sense of disappointment exhibited by some individuals when visiting or going on vacation to Paris, who feel that Paris is not as beautiful as they had expected it to be. The syndrome is characterized by[citation needed] a number of psychiatric symptoms such as acute delusional states, hallucinations, feelings of persecution (perceptions of being a victim of prejudice, aggression, or hostility from others), derealization, depersonalization, anxiety, and also psychosomatic manifestations such as dizziness, tachycardia, sweating, and others, such as vomiting. Similar syndromes include Jerusalem syndrome and Stendhal syndrome. The condition is commonly viewed as a severe form of culture shock. It is particularly noted among Japanese travellers.[citation needed] It is not listed as a recognised condition in the Diagnostic and Statistical Manual of Mental Disorders. ## Contents * 1 History * 2 Susceptibility * 3 See also * 4 Bibliography * 5 External links ## History[edit] Dr. Hiroaki Ota, a Japanese psychiatrist working at the Sainte-Anne Hospital Center in France, coined the term in the 1980s[1] and published a book of the same name[2] in 1991. Katada Tamami of Nissei Hospital wrote of a manic-depressive Japanese patient suffering from Paris syndrome in 1998.[3] In 2004, Dr. Ota and coauthors wrote in a French psychiatric journal[4] that France was the only European country to offer specialized care to Japanese citizens in their own language, as an agreement between the Japanese Embassy and Dr. Ota's department in the Sainte-Anne Hospital. In the article, they state that, between 1988 and 2004, only 63 Japanese patients were hospitalized and referred to Dr. Ota. 50% were between 20 and 30 years old. Of the 63 patients, 48 were diagnosed with schizophrenic or other psychotic disorders. Later work by Youcef Mahmoudia, a physician with the hospital Hôtel-Dieu de Paris, indicates that Paris syndrome is "psychopathology related to travel, rather than a syndrome of the traveler."[5] He theorized that the excitement resulting from visiting Paris causes the heart to accelerate, causing giddiness and shortness of breath, which results in hallucinations in the manner similar to (although spurring from opposite causes) the Stendhal syndrome described by Italian psychiatrist Graziella Magherini in her book La sindrome di Stendhal.[6] Although the BBC reported in 2006 that the Japanese embassy in Paris had a "24-hour hotline for those suffering from severe culture shock",[1] the Japanese embassy states no such hotline exists.[7][8] Also in 2006, Miyupi Kusama, of the Japanese embassy in Paris, told The Guardian "There are around 20 cases a year of the syndrome and it has been happening for several years", and that the embassy had repatriated at least four Japanese citizens that year.[9] However, in 2011, the embassy stated that, despite media reports to the contrary, it did not repatriate Japanese nationals suffering from Paris syndrome.[10] ## Susceptibility[edit] Japanese tourists in Paris Of the estimated 1.1 million annual Japanese tourists in Paris,[11] the number of reported cases is small. A journal[which?] also identified two types of the affliction: Those who have previous history of psychiatric problems and those without morbid history who exhibit the delayed-expression type.[12] In an interview with Slate.fr, Dr. Youcef Mahmoudia, a psychiatrist at the Hôtel-Dieu in Paris, stated that of the fifty pathological travelers hospitalized each year, only 3–5% are Japanese.[10] The French newspaper Libération wrote an article on the syndrome in 2004. In the article, Mario Renoux, the president of the Franco-Japanese Medical Association, states that media and touristic advertising are primarily responsible for creating this syndrome.[13] Renoux indicates that while magazines often depict Paris as a place where most people on the street look like models and most women dress in high fashion brands, in reality neither van Gogh nor models are on the street corners of Paris. In this view, the disorder is caused by positive representations of the city in popular culture, which leads to immense disappointment as the reality of experiencing the city is very different from expectations: tourists are confronted with an overcrowded and littered city (especially if compared to Japanese metropolis) and a less than welcoming attitude by French hospitality workers like shopkeepers, restaurant and hotel personnel without considering the higher safety risks to which tourists used to safer cities are suddenly exposed. In 2014, Bloomberg Pursuits reported the syndrome also affected a few of the million annual Chinese tourists in Paris. Jean-Francois Zhou, president of the association of Chinese travel agencies in France (Association Chinoise des Agences de Voyages en France), said "Chinese people romanticize France, they know about French literature and French love stories… But some of them end up in tears, swearing they’ll never come back."[14] The article cited a 2012 survey from the Paris Tourism Office, in which safety and cleanliness received low scores, and also noted that the Paris Police Prefecture website was made available in Chinese,[15] in addition to English and French. However, Michel Lejoyeux, head of psychiatry at Bichat–Claude Bernard Hospital in Paris, noted in an interview that "Traveler’s syndrome is an old story", and pointed to Stendhal syndrome. ## See also[edit] * France portal * Japanese community of Paris * Psychosis ## Bibliography[edit] Notes 1. ^ a b Wyatt, Caroline (20 December 2006). "'Paris Syndrome' strikes Japanese". BBC News. Retrieved 4 November 2009. 2. ^ Ota, Hiroaki (1991). パリ症候群 [Pari shōkōgun] (in Japanese). TRAJAL Books (ja). ISBN 978-489559233-8. 3. ^ Tamami, Katada (1998). パリ症候群の1症例についての考察 [Reflexions on a case of Paris syndrome]. 日生病院医学雑誌 [Journal of the Nissei Hospital] (in Japanese). Science Links Japan. 26 (2): 127–132. ISSN 0301-2581. Archived from the original on 30 October 2013. Retrieved 5 November 2009. 4. ^ Viala, A.; Ota, H.; Vacheron, M.N.; Martin, P.; Caroli, F. (June 2004). "Les japonais en voyage pathologique à Paris: un modèle original de prise en charge transculturelle" [Japanese pathological trip to Paris: an original model of cross-cultural management]. Nervure Supplément (in French). 17 (5): 31–34. Archived from the original on 8 October 2019. Retrieved 11 July 2016. 5. ^ Xaillé, Anne (21 November 2002). "Voyage pathologique: Voyager rend-il fou ?" [Travel pathological: Traveling makes you crazy?] (in French). Assistance Publique – Hôpitaux de Paris. Archived from the original on 29 September 2011. Retrieved 9 November 2018. "le docteur Mahmoudia préfère parler de voyage pathologique ou de psychopathologie liée au voyage, plutôt que de syndrome du voyageur." 6. ^ Magherini, Graziella (1995). La sindrome di Stendhal (in Italian) (1995 ed.). Ponte alle Grazie. ISBN 88-7928-308-1. Total pages: 219 7. ^ "Contacts". Ambassade du Japon en France (in French). Ministry of Foreign Affairs of Japan. 7 January 2020. Archived from the original on 1 January 2020. Retrieved 12 April 2020. "En dépit d'informations erronées publiées/citées dans (par) divers médias, l'Ambassade du Japon en France vous informe ne disposer d'aucun service téléphonique dévolu au soi-disant "syndrome de Paris" et ne répondra à aucune sollicitation de quelque nature que ce soit concernant ce sujet." 8. ^ ご意見・ご相談 | 在フランス日本国大使館. Embassy of Japan in Paris (in Japanese). Ministry of Foreign Affairs of Japan. 16 November 2018. Archived from the original on 16 July 2019. Retrieved 12 April 2020. "※複数のメディアにおいて間違った報道がなされているようですが、在仏大使館では「パリ症候群」のホットラインやこれに関するいかなる対応もしておりません。御理解のほど宜しくお願いいたします" 9. ^ Chrisafis, Angelique (25 October 2006). "Paris syndrome hits Japanese". The Guardian. London. Retrieved 4 November 2009. 10. ^ a b Georgen, Annabelle (26 December 2011). "Paris ou le choc de la réalité" [Paris or the shock of reality]. Slate (in French). Archived from the original on 31 August 2019. Retrieved 12 April 2020. 11. ^ Haupt, Tomas (9 December 2019). "Japanese Tourists Show Growing Interest in French Destinations". Tourism Review. Retrieved 12 April 2020. 12. ^ Robinson, Mike; Picard, David (2016). Emotion in Motion: Tourism, Affect and Transformation. Oxon: Routledge. p. 102. ISBN 978-1-40942133-7. 13. ^ Levy, Audrey (13 December 2004). "Des Japonais entre mal du pays et mal de Paris" [The Japanese between homesick and Paris sick]. Libération (in French). Archived from the original on 19 December 2019. Retrieved 25 November 2014. 14. ^ Nussbaum, Ania (14 August 2014). "The Paris Syndrome Drives Chinese Tourists Away". Bloomberg. Retrieved 12 April 2020. 15. ^ "Préfecture de police (中文)". Retrieved 12 April 2020. ## External links[edit] * Paris Syndrome, a 2010 short documentary * v * t * e City of Paris Arrondissements 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th 12th 13th 14th 15th 16th 17th 18th 19th 20th * Airports * Charles de Gaulle * Orly * Architecture * Era of absolutism * Bridges * Culture * Cycling * Vélib' Métropole * Economy * Education * History (timeline) * Landmarks * Libraries * Mayors * Museums * List * Music * Tallest buildings * Syndrome * Religion * Archdiocese * Squares * Topography * Transport * Métro * Transilien * Tramways * RER * Tourism * Grand Paris * Paris metropolitan area * Île-de-France * France * v * t * e Tourism in Paris Landmarks * Arc de Triomphe * Arc de Triomphe du Carrousel * Arènes de Lutèce * Bourse * Catacombs * Conciergerie * Eiffel Tower * Gare d'Austerlitz * Gare de l'Est * Gare de Lyon * Gare du Nord * Gare Montparnasse * Gare Saint-Lazare * Grand Palais and Petit Palais * Institut de France * Jeanne d'Arc * Les Invalides * Louvre Pyramid * Luxor Obelisk * Odéon * Opéra Bastille * Opéra Garnier * Panthéon * Philharmonie de Paris * Place Diana * Flame of Liberty * Porte Saint-Denis * Porte Saint-Martin * Sorbonne * Tour Montparnasse Museums (list) * Bibliothèque nationale * Carnavalet * Centre Georges Pompidou * Cité des Sciences et de l'Industrie * Galerie nationale du Jeu de Paume * Louis Vuitton Foundation * Musée des Arts Décoratifs * Musée des Arts et Métiers * Musée d'Art et d'Histoire du Judaïsme * Musée d'Art Moderne de Paris * Maison de Balzac * Musée Bourdelle * Musée de la Cinémathèque * Musée Cognacq-Jay * Musée Grévin * Musée Guimet * Maison de Victor Hugo * Musée Jacquemart-André * Musée du Louvre * Musée Marmottan Monet * Musée de Montmartre * Musée National d'Art Moderne * Musée national Eugène Delacroix * Musée national Gustave Moreau * Musée national des Monuments Français * Muséum national d'histoire naturelle * Musée de Cluny – Musée national du Moyen Âge * Musée de l'Orangerie * Musée d'Orsay * Musée Pasteur * Musée Picasso * Musée du quai Branly * Musée Rodin * Palais de la Légion d'Honneur * Musée de la Légion d'honneur * Musée de la Vie romantique Religious buildings * Alexander Nevsky Cathedral * American Cathedral * American Church * Chapelle expiatoire * Grand Mosque * Grand Synagogue * La Madeleine * Notre-Dame de Paris * Notre-Dame-de-Bonne-Nouvelle * Notre-Dame-de-Lorette * Notre-Dame-des-Victoires * Sacré-Cœur * Saint Ambroise * Saint-Augustin * Saint-Étienne-du-Mont * Saint-Eustache * Saint-François-Xavier * Saint-Germain-des-Prés * Saint-Germain l'Auxerrois * Saint-Gervais-Saint-Protais * Saint-Jacques Tower * Saint-Jean-de-Montmartre * Saint-Paul-Saint-Louis * Saint-Pierre de Montmartre * Saint-Roch * Saint-Sulpice * Saint-Vincent-de-Paul * Sainte-Chapelle * Sainte-Clotilde * Sainte-Trinité * Temple du Marais * Val-de-Grâce Hôtels particuliers and palaces * Élysée Palace * Hôtel de Beauvais * Hôtel de Charost * Hôtel de Crillon * Hôtel d'Estrées * Hôtel de la Païva * Hôtel de Pontalba * Hôtel de Sens * Hôtel de Soubise * Hôtel de Sully * Hôtel de Ville * Hôtel Lambert * Hôtel Matignon * Luxembourg Palace * Petit Luxembourg * Palais Bourbon * Palais de Justice * Palais-Royal Bridges, streets, areas, squares and waterways * Avenue de l'Opéra * Avenue Foch * Avenue George V * Boulevard de la Madeleine * Boulevard de Sébastopol * Canal de l'Ourcq * Canal Saint-Martin * Champ de Mars * Champs-Élysées * Covered passages * Galerie Véro-Dodat * Choiseul * Panoramas * Galerie Vivienne * Havre * Jouffroy * Brady * Latin Quarter * Le Marais * Montmartre * Montparnasse * Place Diana * Place Dauphine * Place de la Bastille * Place de la Concorde * Place de la Nation * Place de la République * Place des Émeutes-de-Stonewall * Place des États-Unis * Place des Pyramides * Place des Victoires * Place des Vosges * Place du Carrousel * Place du Châtelet * Place du Tertre * Place Saint-Michel * Place Vendôme * Pont Alexandre III * Pont d'Iéna * Pont de Bir-Hakeim * Pont des Arts * Pont Neuf * Port du Louvre * Rive Gauche * Rue Basse * Rue Bonaparte * Rue Charlemagne * Rue d'Argenteuil * Rue de la Ferronnerie * Rue de la Paix * Rue de la Sourdière * Rue de Montmorency * Rue de Richelieu * Rue de Rivoli * Rue de Vaugirard * Rue des Francs-Bourgeois * Rue des Lombards * Rue du Faubourg Saint-Honoré * Rue Elzévir * Rue Molière * Rue Montorgueil * Rue Radziwill * Rue Rambuteau * Rue Mondétour * Rue Pastourelle * Rue des Rosiers * Rue Saint-Honoré * Rue Saint-Denis * Rue Sainte-Anne * Saint-Germain-des-Prés * Trocadéro * Viaduc d'Austerlitz Parks and gardens * Bois de Boulogne * Jardin d'Acclimatation * Bois de Vincennes * Parc floral * Jardin du Luxembourg * Parc André Citroën * Parc Clichy-Batignolles * Parc de Belleville * Parc de Bercy * Parc de la Butte-du-Chapeau-Rouge * Parc des Buttes Chaumont * Parc Georges-Brassens * Parc Monceau * Parc Montsouris * Tuileries Garden * Coulée verte René-Dumont Sport venues * AccorHotels Arena * Auteuil Hippodrome * Halle Georges Carpentier * Longchamp Hippodrome * Parc des Princes * Piscine Molitor * Stade Jean Bouin * Stade Pershing * Stade Pierre de Coubertin * Stade Roland Garros * Stade Sébastien Charléty * Vélodrome de Vincennes * Vincennes Hippodrome Cemeteries * Montmartre Cemetery * Montparnasse Cemetery * Passy Cemetery * Père Lachaise Cemetery * Oscar Wilde's tomb * Picpus Cemetery Région parisienne * Basilica of Saint-Denis * Château d'Écouen * Château de Chantilly * Château de Fontainebleau * Château de Malmaison * Château de Rambouillet * Château de Saint-Germain-en-Laye * Château de Sceaux * Château and Gardens of Versailles * Château de Vincennes * La Défense * Grande Arche * Paris La Défense Arena * Disneyland Paris * Disneyland Park * Walt Disney Studios Park * Exploradôme * Fort Mont-Valérien * Mémorial de la France combattante * Suresnes American Cemetery and Memorial * France Miniature * Musée de l'air et de l'espace * Musée Fragonard d'Alfort * Parc Astérix * Parc de Saint-Cloud * Provins * La Roche-Guyon * Sèvres – Cité de la céramique * Stade de France * Vaux-le-Vicomte Culture and events * Bastille Day military parade * Fête de la Musique * Nuit Blanche * Paris Air Show * Paris-Plages * Republican Guard * Solidays Other * Axe historique * Bateau-Lavoir * Bateaux Mouches * Café des 2 Moulins * Café Procope * Fountains in Paris * La Ruche * Les Deux Magots * Maxim's * Moulin de la Galette * Moulin Rouge * Paris Métro * entrances * Montmartre Funicular * Paris Musées * Paris Syndrome * Paris Zoological Park * Pyramide inversée *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Paris syndrome

None

wikipedia

https://en.wikipedia.org/wiki/Paris_syndrome

{"wikidata": ["Q1462780"]}

Not to be confused with Tietze syndrome. Tietz syndrome Other namesHypopigmentation-deafness syndrome Tietz syndrome has an autosomal dominant pattern of inheritance. SpecialtyPediatrics Tietz syndrome, also called Tietz albinism-deafness syndrome or albinism and deafness of Tietz,[1] is an autosomal dominant[2] congenital disorder characterized by deafness and leucism.[3] It is caused by a mutation in the microphthalmia-associated transcription factor (MITF) gene.[2][4] Tietz syndrome was first described in 1963 by Walter Tietz (1927–2003) a German Physician working in California.[5] ## Contents * 1 Presentation * 2 Cause * 3 Treatment * 4 See also * 5 References * 6 External links ## Presentation[edit] Tietz syndrome is characterized by profound hearing loss from birth, white hair and pale skin (hair color may darken over time to blond or red).[citation needed] The hearing loss is caused by abnormalities of the inner ear (sensorineural hearing loss) and is present from birth. Individuals with Tietz syndrome often have skin and hair color that is lighter than those of other family members. Tietz syndrome also affects the eyes. The iris in affected individuals is blue, and specialized cells in the eye called retinal pigment epithelial cells lack their normal pigment. The changes to these cells are generally detectable only by an eye examination; it is unclear whether the changes affect vision.[6] ## Cause[edit] Tietz syndrome is caused by mutations in the MITF gene, located on human chromosome 3p14.1-p12.3.[2][4][7] It is inherited in an autosomal dominant manner.[2] This indicates that the defective gene responsible for a disorder is located on an autosome (chromosome 3 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.[citation needed] ## Treatment[edit] This section is empty. You can help by adding to it. (April 2017) ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 103500 2. ^ a b c d Smith SD, Kelley PM, Kenyon JB, Hoover D (Jun 2000). "Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF" (Free full text). J. Med. Genet. 37 (6): 446–448. doi:10.1136/jmg.37.6.446. PMC 1734605. PMID 10851256. 3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 925. ISBN 978-1-4160-2999-1. 4. ^ a b Amiel J, Watkin PM, Tassabehji M, Read AP, Winter RM (Jan 1998). "Mutation of the MITF gene in albinism-deafness syndrome (Tietz syndrome)". Clin. Dysmorphol. 7 (1): 17–20. doi:10.1097/00019605-199801000-00003. PMID 9546825. 5. ^ Tietz W (Sep 1963). "A Syndrome of Deaf-Mutism Associated with Albinism Showing Dominant Autosomal Inheritance". Am. J. Hum. Genet. 15 (3): 259–264. PMC 1932384. PMID 13985019. 6. ^ "Tietz syndrome". Genetics Home Reference. 2016-02-22. Retrieved 2016-03-01. 7. ^ Online Mendelian Inheritance in Man (OMIM): 156845 ## External links[edit] Classification D * ICD-10: E70.3 (ILDS E70.358) * OMIM: 103500 * MeSH: C536919 * DiseasesDB: 34108 External resources * Orphanet: 42665 * Tietz syndrome; Albinism and complete nerve deafness at NIH's Office of Rare Diseases * v * t * e Pigmentation disorders/Dyschromia Hypo-/ leucism Loss of melanocytes Vitiligo * Quadrichrome vitiligo * Vitiligo ponctué Syndromic * Alezzandrini syndrome * Vogt–Koyanagi–Harada syndrome Melanocyte development * Piebaldism * Waardenburg syndrome * Tietz syndrome Loss of melanin/ amelanism Albinism * Oculocutaneous albinism * Ocular albinism Melanosome transfer * Hermansky–Pudlak syndrome * Chédiak–Higashi syndrome * Griscelli syndrome * Elejalde syndrome * Griscelli syndrome type 2 * Griscelli syndrome type 3 Other * Cross syndrome * ABCD syndrome * Albinism–deafness syndrome * Idiopathic guttate hypomelanosis * Phylloid hypomelanosis * Progressive macular hypomelanosis Leukoderma w/o hypomelanosis * Vasospastic macule * Woronoff's ring * Nevus anemicus Ungrouped * Nevus depigmentosus * Postinflammatory hypopigmentation * Pityriasis alba * Vagabond's leukomelanoderma * Yemenite deaf-blind hypopigmentation syndrome * Wende–Bauckus syndrome Hyper- Melanin/ Melanosis/ Melanism Reticulated * Dermatopathia pigmentosa reticularis * Pigmentatio reticularis faciei et colli * Reticulate acropigmentation of Kitamura * Reticular pigmented anomaly of the flexures * Naegeli–Franceschetti–Jadassohn syndrome * Dyskeratosis congenita * X-linked reticulate pigmentary disorder * Galli–Galli disease * Revesz syndrome Diffuse/ circumscribed * Lentigo/Lentiginosis: Lentigo simplex * Liver spot * Centrofacial lentiginosis * Generalized lentiginosis * Inherited patterned lentiginosis in black persons * Ink spot lentigo * Lentigo maligna * Mucosal lentigines * Partial unilateral lentiginosis * PUVA lentigines * Melasma * Erythema dyschromicum perstans * Lichen planus pigmentosus * Café au lait spot * Poikiloderma (Poikiloderma of Civatte * Poikiloderma vasculare atrophicans) * Riehl melanosis Linear * Incontinentia pigmenti * Scratch dermatitis * Shiitake mushroom dermatitis Other/ ungrouped * Acanthosis nigricans * Freckle * Familial progressive hyperpigmentation * Pallister–Killian syndrome * Periorbital hyperpigmentation * Photoleukomelanodermatitis of Kobori * Postinflammatory hyperpigmentation * Transient neonatal pustular melanosis Other pigments Iron * Hemochromatosis * Iron metallic discoloration * Pigmented purpuric dermatosis * Schamberg disease * Majocchi's disease * Gougerot–Blum syndrome * Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis * Lichen aureus * Angioma serpiginosum * Hemosiderin hyperpigmentation Other metals * Argyria * Chrysiasis * Arsenic poisoning * Lead poisoning * Titanium metallic discoloration Other * Carotenosis * Tar melanosis Dyschromia * Dyschromatosis symmetrica hereditaria * Dyschromatosis universalis hereditaria See also * Skin color * Skin whitening * Tanning * Sunless * Tattoo * removal * Depigmentation * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Tietz syndrome

c0391816

wikipedia

https://en.wikipedia.org/wiki/Tietz_syndrome

{"gard": ["7772"], "mesh": ["C536919"], "umls": ["C0391816"], "icd-10": ["E70.3"], "orphanet": ["42665"], "wikidata": ["Q7801152"]}

A number sign (#) is used with this entry because of evidence that lissencephaly-5 (LIS5) is caused by homozygous or compound heterozygous mutation in the LAMB1 gene (150240) on chromosome 7q31. Description Lissencephaly-5 is an autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development (summary by Radmanesh et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432). Clinical Features Radmanesh et al. (2013) reported a consanguineous Egyptian family in which 3 sibs had severely delayed psychomotor development, hydrocephalus, posterior encephalocele, and cobblestone brain malformations consistent with lissencephaly. Brain imaging showed abnormal cortical gyri and sulci, white matter abnormalities, and brainstem and cerebellar hypoplasia. Cortical gyration abnormalities showed a posterior to anterior gradient. Below the cortical layer was evidence of gray matter laminar heterotopia. There were also myelination abnormalities. Although the brain malformations were reminiscent of muscular dystrophy-dystrogycanopathies (see, e.g., MDDGA1, 236670), the patients did not have significant ocular abnormalities or muscle involvement. An unrelated Turkish child, born of consanguineous parents, had a similar severe phenotype with intrauterine hydrocephalus, severe developmental delay, and seizures. Brain imaging showed cobblestone lissencephaly and band-like heterotopia with posterior predominance. Tonduti et al. (2015) reported 2 sibs, born of unrelated parents, with a severe progressive neurodegenerative disorder. The phenotypes were slightly different. The older patient presented with infantile spasms and static right hemiplegia associated with a left porencephalic cavity on brain imaging. At age 12 years, she showed resurgence of the epilepsy and progressive deterioration. At age 19, she had spastic tetraplegia with loss of ambulation, mental deficiency, and macrocephaly. Other features included optic atrophy and anterior subcapsular lens opacities; deafness was detected at age 23. At age 30, she had stable epilepsy, but progressive mental deterioration. Her older brother presented with well-controlled absence seizures at age 7 years. After a fall at age 16, he developed generalized resistant seizures and progressive gait difficulties associated with neurocognitive deterioration. He lost the ability to walk at age 24, and physical examination showed spastic paraplegia with cerebellar signs. Other features included retinal vascular tortuosities and subcapsular lens opacities as well as episodes of stupor coma induced by stress. At age 34, he was totally dependent. Brain imaging of both patients showed supratentorial white matter abnormalities with cysts and vacuoles in the deep white matter. Agyria/lissencephaly was apparent in the occipital region, and polymicrogyria was observed in the frontal regions. Follow-up over 10 years showed progressive white matter atrophy with enlargement of the ventricles. Inheritance The transmission pattern of LIS5 in the families reported by Radmanesh et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 4 patients from 2 unrelated consanguineous families with lissencephaly-5, Radmanesh et al. (2013) identified 2 different homozygous loss-of-function mutations in the LAMB1 gene (150240.0001 and 150240.0002, respectively). Both mutations were identified by exome sequencing. The findings suggested a role for LAMB1 at the basement membrane, where it mediates both the integrity of the glia limitans and attachment of radial glial endfeet during neuronal migration. In 2 adult sibs, born of unrelated parents, with LIS5, Tonduti et al. (2015) identified compound heterozygous mutations in the LAMB1 gene: a frameshift mutation (150240.0003) and a missense substitution (C481F; 150240.0004). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly due to hydrocephalus Ears \- Deafness (in some patients) Eyes \- Optic atrophy (in some patients) \- Lens opacities (in some patients) NEUROLOGIC Central Nervous System \- Hydrocephalus \- Psychomotor retardation \- Mental deficiency, progressive \- Hypotonia \- Seizures \- Spastic paraplegia \- Cobblestone lissencephaly (posterior brain regions more affected than anterior regions) \- Subcortical band heterotopia \- Occipital encephalocele \- Cerebellar hypoplasia \- Brainstem hypoplasia \- Leukoencephalopathy \- White matter abnormalities \- White matter cysts \- Porencephaly \- White matter atrophy, progressive MISCELLANEOUS \- Onset in the first decade (range infancy to later childhood) \- Progressive disorder \- Episodic neurologic deterioration with stress \- Variable severity \- Six patients from 3 unrelated families have been reported (last curated April 2016) MOLECULAR BASIS \- Caused by mutation in the beta-1 laminin gene (LAMB1, 150240.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

LISSENCEPHALY 5

c3554657

omim

https://www.omim.org/entry/615191

{"doid": ["0050453"], "omim": ["615191"], "orphanet": ["352682"], "synonyms": ["Cobblestone lissencephaly without muscular or eye involvement", "Lissencephaly type 2 without muscular or eye involvement", "Lissencephaly type 2 without muscular or ocular involvement"]}

## Clinical Features In 2 half brothers with the same mother, Chitayat et al. (1991) described the Robin sequence and facial and digital anomalies. Both sons, aged 6 months and 4 years, had normal psychomotor development. The digital features consisted of tapering fingers, hyperconvex nails, clinodactyly of the fifth fingers, and short distal phalanges. The older boy's thumbs had a finger-like shape and the distal phalanx was markedly shorter than the proximal one. The first metacarpophalangeal joints could be easily subluxated. In addition to retrognathia, both boys showed high forehead and frontal bossing. The mother was not related to either of her husbands, and all 3 were of French Canadian origin. The mother had no abnormalities. Nails \- Hyperconvex nails Inheritance \- X-linked Mouth \- Cleft palate \- Glossoptosis Facies \- High forehead \- Frontal bossing \- Micrognathia Limbs \- Tapered fingers \- Fifth finger clinodactyly \- Short distal phalanges \- Finger-shaped thumbs \- Easily subluxated first metacarpophalangeal joints ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

PIERRE ROBIN SEQUENCE WITH FACIAL AND DIGITAL ANOMALIES

c2931064

omim

https://www.omim.org/entry/311895

{"mesh": ["C564078"], "omim": ["311895"], "orphanet": ["2888"]}

## Summary ### Clinical characteristics. CATSPER-related male infertility results from abnormalities in sperm and can be either CATSPER-related nonsyndromic male infertility (NSMI) or the deafness-infertility syndrome (DIS) when associated with non-progressive prelingual sensorineural hearing loss. Males with NSMI have infertility while females have no symptoms. Males with DIS have both infertility and hearing loss, while females have only hearing loss. Routine semen analysis typically identifies abnormalities in sperm number, morphology, and motility. Otologic examination and audiologic assessment can identify hearing loss. ### Diagnosis/testing. The diagnosis of CATSPER-related NSMI is established in males by the identification of biallelic pathogenic variants in CATSPER1. The diagnosis of DIS is established in both males and females by the identification of biallelic contiguous-gene deletions at chromosome 15q15.3 that includes both CATSPER2 and STRC. ### Management. Treatment of manifestations: For infertile males with DIS or CATSPER-related NSMI, assisted reproductive technologies such as intracytoplasmic sperm injection are likely to be an effective fertility option. For males with DIS, treatment of hearing loss is best achieved by fitting hearing aids for amplification and special educational assistance for school-age children. Agents/circumstances to avoid: For individuals with DIS, exposure to loud noise. Evaluation of relatives at risk: For sibs at risk for DIS, audiologic testing in infancy or early childhood to enable early management of hearing loss. ### Genetic counseling. CATSPER-related NSMI and DIS are inherited in an autosomal recessive manner. When both parents are carriers for pathogenic variants, each child has a 25% chance of inheriting both pathogenic variants, a 50% chance of inheriting one pathogenic variant and being an asymptomatic carrier, and a 25% chance of inheriting neither pathogenic variant. Males who inherit two CATSPER1 pathogenic variants will be infertile; females who inherit two CATSPER1 pathogenic variants will have no signs/symptoms. Males who inherit two CATSPER2-STRC deletions will be infertile and deaf; females who inherit two CATSPER2-STRC deletions will be deaf. If the pathogenic variants have been identified in an affected family member, prenatal testing for at-risk pregnancies is possible through laboratories offering either prenatal testing for the gene of interest or custom testing. ## Diagnosis CATSPER-related male infertility results from abnormalities in sperm and can be either: * Nonsyndromic (CATSPER-related nonsyndromic male infertility [NSMI]); or * Associated with non-progressive prelingual sensorineural hearing loss (deafness-infertility syndrome [DIS]). ### Suggestive Findings CATSPER-related male infertility should be suspected in individuals with the following clinical features and semen analysis. Clinical features * Male factor infertility * Hearing loss in either a male or female: * In DIS, prelingual hearing loss in the moderate-to-severe range across all frequencies (0.25 kHz – 8 kHz) * Normal vestibular function Semen analysis. Routine semen analysis assesses sperm number, morphology, and motility and the function of the genital tract (semen volume and pH) [WHO 1999] (Table 1). Note: Although routine semen analysis effectively identifies azoospermia, changes in sperm morphology and motility can be missed unless the analysis includes measurement of sperm motility (e.g., path velocity, progressive velocity, and track speed). * NSMI. While the pH of the semen was in the normal range, examination of all other parameters revealed non-motile sperm or sperm motility below the normal threshold, low sperm count, an increased number of abnormally structured spermatozoa, and reduced semen volume [Avenarius et al 2009]. * DIS. Semen analysis of males with DIS is normal for sperm count and semen volume, but sperm morphology and motility are abnormal. ### Table 1. Semen Analysis View in own window TestCATSPER-Related Male InfertilityNormal 1 NSMIDIS Ejaculate volume0.4-1.0 mL1-4 mL1.5-5 mL pH7.5-8.0Normal>7.2 Sperm concentrationNormal60-78 million/mL>20 million/mL Total sperm number (million/ejaculate)10.4-12>40>40 Percent motility (% motile)0%-50%1%-5%>50% Forward progression (scale 0-4)NormalNormal>2 Morphology (% normal)20%-65%9%-12%>30% Sperm agglutination (scale 0-3)NormalNormal<2 Viscosity (scale 0-4)NormalNormal – 3+<3 DIS = deafness-infertility syndrome; NSMI = nonsyndromic male infertility 1\. Values from ASRM Practice Committee [Male Infertility Best Practice Policy Committee 2006] ### Establishing the Diagnosis #### Nonsyndromic Male Infertility (NSMI) The diagnosis of CATSPER-related NSMI is established in males by the identification of biallelic loss-of-function pathogenic variants in CATSPER1 on molecular genetic testing (see Table 2). Single-gene testing. Sequence analysis of CATSPER1 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. Alternate testing strategy for NSMI * A multigene panel that includes CATSPER1 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. #### Deafness-Infertility Syndrome (DIS) The diagnosis of CATSPER-related DIS is established in both males and females by the identification of biallelic contiguous-gene deletions at chromosome 15q15.3 that includes both CATSPER2 and STRC. Chromosomal microarray (CMA) using oligonucleotide or SNP arrays can detect a contiguous-gene deletion involving CATSPER2 and STRC in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the 15q15.3 region. ### Table 2. Molecular Genetic Testing Used in CATSPER-Related Male Infertility View in own window Gene 1 or Deletion 2MethodProportion of Probands with Pathogenic Variants 3 Detectable by Method NSMIDIS CATSPER1Sequence analysis 42/2 5NA Gene-targeted deletion/duplication analysis 6Unknown 7NA Homozygous deletion at 15q15.3 including CATSPER2 and STRCCMA/array CGH 8NA100% 9 UnknownNAUnknown 10Unknown 10 DIS = deafness-infertility syndrome; NA = not applicable; NSMI = nonsyndromic male infertility 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for details of the deletion and genes of interest included in the region. 3\. See Molecular Genetics for information on allelic variants detected in this gene. 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Two families with homozygous loss-of-function variants in CATSPER1 have been reported [Avenarius et al 2009]. 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 7\. No data on detection rate of gene-targeted deletion/duplication analysis in individuals with NSMI are available. 8\. Chromosomal microarray analysis (CMA) using oligonucleotide or SNP arrays or array comparative genomic hybridization (array CGH) using fluorescent probesThese approaches are in clinical use targeting the 15q15.3 region. Note: The 15q15.3 deletion may not have been detectable by older oligonucleotide or BAC platforms. 9\. In all cases of CATSPER2-related DIS the entire CATSPER1 gene, as well as STRC, has been deleted as part of a contiguous deletion (see Molecular Genetics). A case of brothers with a heterozygous CATSPER2 deletion and an apparent NSMI phenotype has been reported; however, given the lack of a second pathogenic variant and no evidence of hearing loss, the cause of NSMI in this family was not clear [Jaiswal et al 2014]. 10\. The contribution of the other CATSPER gene family members (CATSPER2, CATSPER3, CATSPER4, CATSPERB, and CATSPERG) to NSMI is unknown [Lobley et al 2003, Liu et al 2007, Cai & Clapham 2008, Wang et al 2009, Hildebrand et al 2010]. ## Clinical Characteristics ### Clinical Description CATSPER-related male infertility includes CATSPER-related nonsyndromic male infertility (NSMI) and the deafness-infertility syndrome (DIS) [Nikpoor et al 2004, Clapham & Garbers 2005, Benoff et al 2007, Hildebrand et al 2010]. #### CATSPER-Related Nonsyndromic Male Infertility (NSMI) CATSPER-related NSMI was reported in two unrelated Iranian families in 2009 [Avenarius et al 2009]. In both families, the affected infertile males were offspring of first-cousin marriages. Females homozygous for the CATSPER1 pathogenic variant and all heterozygous individuals within a family have normal fertility. #### Deafness-Infertility Syndrome (DIS) Infertility. All males homozygous for CATSPER2-STRC deletion are infertile. Semen analysis is typically abnormal. For example, in one affected male more than 88% of sperm were malformed (mainly thin heads, micro- and irregular acrosomes) and approximately 30% of sperm had short, coiled flagella [Zhang et al 2007]. Following liquidation fewer than 5% of sperm had full swimming capacity. Similar defects were observed in other affected males from the four families [Avidan et al 2003, Zhang et al 2007, Smith et al 2013]. Hearing loss. All affected males and females who are homozygous for the deletion of CATSPER2-STRC have hearing loss, although onset and severity of hearing loss may vary. * Typically, the hearing loss in DIS is diagnosed in early childhood. It is non-progressive; vestibular function is normal. * In all reported affected males, the degree of hearing loss is moderate to severe across all frequencies (0.25 kHz - 8 kHz). This auditory phenotype is comparable to that observed in persons with DFNB16 [Villamar et al 1999, Verpy et al 2001]. Note: Knijnenburg and colleagues reported a male of nonconsanguineous parentage with a complex phenotype that included intellectual disability, short stature, dysmorphic features, and hearing loss associated with a homozygous CATSPER2-STRC contiguous-gene deletion. Sperm motility could not be assessed in the proband, who was age ten years. The more severe phenotype in this individual may represent one end of a broader phenotypic spectrum associated with homozygous deletion of 15q15.3, or the intellectual disability and dysmorphic features may be unrelated or only partially related to the 15q15.3 deletion [Knijnenburg et al 2009]. ### Genotype-Phenotype Correlations Since only two pathogenic loss-of-function variants for CATSPER-related NSMI in two unrelated families have been identified [Avenarius et al 2009], meaningful genotype-phenotype correlations are not possible. Similarly, all families with DIS have homozygous deletions at 15q15.3 involving loss of CATSPER2 and STRC [Avidan et al 2003, Zhang et al 2007, Knijnenburg et al 2009, Smith et al 2013, Gu et al 2015]. ### Historical Perspective DIS was first identified by Avidan and colleagues in a French family segregating deafness, infertility, and congenital dyserythropoietic anemia type 1 (caused by pathogenic variants in CDAN1). The three affected males were homozygous for a p.Asn598Ser missense variant in CDAN1 and were also homozygous for a contiguous-gene deletion that involved CATSPER2 and STRC [Avidan et al 2003]. Four years later, three unrelated Iranian families that segregated only deafness and infertility secondary to deletion of CATSPER2 and STRC were identified [Zhang et al 2007]. Zhang and colleagues designated this new syndromic form of hearing loss deafness-infertility syndrome (DIS). None of these families share similar deletions. ### Nomenclature Deafness-infertility syndrome is also known as sensorineural deafness and male infertility. CATSPER-related nonsyndromic male infertility is also referred to as autosomal recessive nonsyndromic male infertility. ### Prevalence The prevalence of CATSPER-related nonsyndromic male infertility (NSMI) is unknown; only two families have been reported. The prevalence of deletions at 15q15.3 involving CATSPER2 and STRC was examined in peripheral blood specimens from 5,152 individuals from the general population by array CGH [Hoppman et al 2013]. Of those, 57 individuals (2 of whom were sibs) were found to be heterozygous for similar deletions including CATSPER2 and STRC, indicating that 1.09% of people in this sample were carriers. If this figure is representative of the general population, this would indicate that approximately one in 40,000 individuals is born with a homozygous deletion of this region, resulting in deafness and, in males, infertility [Hoppman et al 2013]. ## Differential Diagnosis Male infertility. In approximately half of the 15% of couples who cannot conceive, the cause is ascribed to male infertility as described by Mosher & Pratt [1990] and Templeton et al [1990]. Causes of male infertility other than pathogenic variants in CATSPER are numerous and include but are not limited to the following: * Obstruction of the ejaculatory ducts (e.g., cystic fibrosis and congenital absence of the vas deferens) (see CFTR-Related Disorders) * Abnormal sperm motility (see Primary Ciliary Dyskinesia) * Immunologic abnormalities (e.g., anti-sperm antibodies) * Infection (e.g., mumps orchitis, epididymitis, urethritis) * Vascular abnormalities (e.g., varicocele) * Trauma * Endocrine abnormalities including congenital adrenal hyperplasia (see 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia), isolated follicle-stimulating hormone deficiency (OMIM 229070), and hyperprolactinemia (OMIM 615555) * Testicular tumor * Exposure to toxic agents (e.g., radiation, chemotherapy agents, heat) * Klinefelter syndrome (47,XXY) * Balanced chromosome rearrangements * Sertoli-cell-only syndrome For review of these differential diagnoses refer to Y Chromosome Infertility: Differential Diagnosis. Molecular genetic testing to attempt to identify the involved gene is appropriate. Pathogenic variants in a large number of genes cause male infertility (a partial list includes CATSPER1, AKAP3, AKAP4, DNAH1, DNAH5, DNAH11, SPATA16, PRM1, PRM2, SYCP1, and SYCP3); as asthenospermia (loss or reduction in spermatozoa motility) is caused by pathogenic variants in CATSPER1 (NSMI) [Avenarius et al 2009] and CATSPER2 (DIS) [Avidan et al 2003, Zhang et al 2007], the CATSPER family should be among the first genes tested. See Spermatogenic failure: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM. Deafness. See Deafness and Hereditary Hearing Loss Overview. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CATSPER-related male infertility, the following evaluations are recommended (if not performed previously as part of the diagnostic evaluation): * In males, pubertal age or older, semen analysis to assess sperm number, motility, and morphology * In males and females with DIS, hearing evaluation including otologic examination and audiologic assessment (including measurement of bone conduction) * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations Infertility. No available treatment can reverse the morphologic and/or motility defects observed in CATSPER-related asthenospermia or asthenoteratospermia (low motility with increased number of abnormal forms). For infertile males, one option is to bypass these morphologic and motility abnormalities using assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) [Smith et al 2013]. This approach has been used successfully in males with DIS [Zhang et al 2007]. Deafness. For males and females with DIS, treatment of hearing loss is best achieved by fitting hearing aids for amplification. For school-age children or adolescents, special educational assistance may also be warranted and, where possible, should be offered. (See Deafness and Hereditary Hearing Loss Overview and Related Genetic Counseling Issues for other issues pertinent to the care of deaf and hard-of-hearing persons.) ### Prevention of Secondary Complications Regardless of its etiology, uncorrected hearing loss has consistent sequelae. Auditory deprivation through age two years is associated with poor reading performance, poor communication skills, and poor speech production. Educational intervention is insufficient to completely remediate these deficiencies. In contrast, early auditory intervention, whether through amplification, otologic surgery, or cochlear implantation, is effective [Smith et al 2005] (see Deafness and Hereditary Hearing Loss Overview). Although decreased cognitive skills and performance in mathematics and reading are associated with deafness, examination of persons with hereditary hearing loss has shown that these deficiencies are not intrinsically linked to the cause of the deafness. Thus, early identification and timely intervention are essential for optimal cognitive development in children with prelingual deafness. ### Surveillance Annual monitoring of hearing loss is not required in individuals with DIS because hearing loss is non-progressive. ### Agents/Circumstances to Avoid Individuals with DIS should avoid exposure to loud noise in the workplace or during recreation. ### Evaluation of Relatives at Risk It is appropriate to evaluate the sibs of a proband with DIS in infancy or early childhood in order to identify as early as possible those who would benefit from early support and management of hearing loss. Evaluations can include: * Molecular genetic testing for the causative contiguous-gene deletion; * Otologic examination and audiologic assessment. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

CATSPER-Related Male Infertility

None

gene_reviews

https://www.ncbi.nlm.nih.gov/books/NBK22925/

{"synonyms": []}

Spondylometaphyseal dysplasia, Kozlowski type is a bone disease characterized by short stature involving the trunk. "Spondylo"refers to the spine (vertebrae), "metaphysis" refers to the wide part of the bone that contains the growth plate (the part of the bone that grows during childhood), and "dysplasia" means abnormal growth. It usually starts in early childhood when poor growth with uneven stature and a waddling gait with bow legs (genu varum) is noticed. Early osteoarthritis of the joints is also common. Other signs and symptoms include small hands and fingers, spine deformities, and X-ray showing short vertebra, mild metaphyseal changes, severe delay in ossification, square, short, flared iliac wings (the broadest part of the pelvic bone) and a flat and irregular hipbone. Spondylometaphyseal dysplasia, Kozlowski type is caused by mutations in the TRPV4 gene. Inheritance is autosomal dominant. Treatment is surgical or the use of braces to align the spine. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Spondylometaphyseal dysplasia, Kozlowski type

c0265280

gard

https://rarediseases.info.nih.gov/diseases/3047/spondylometaphyseal-dysplasia-kozlowski-type

{"mesh": ["C535797"], "omim": ["184252"], "orphanet": ["93314"], "synonyms": ["Dysmorphism arthrogryposis skeletal maturation advanced", "Jequier-Kozlowski syndrome", "Skeletal dysplasia Jequier-Kozlowski type", "SMD Kozlowski type", "Jequier Kozlowski skeletal dysplasia"]}

Wrinkly skin syndrome (WSS) is characterized by wrinkling of the skin of the dorsum of the hands and feet, an increased number of palmar and plantar creases, wrinkled abdominal skin, multiple skeletal abnormalities (joint laxity and congenital hip dislocation), late closing of the anterior fontanel, microcephaly, pre- and postnatal growth retardation, developmental delay and facial dysmorphism (a broad nasal bridge, downslanting palpebral fissures and hypertelorism). ## Epidemiology Prevalence is unknown but only around 30 cases have been reported in the literature so far. ## Clinical description Although the clinical picture is milder, WSS also shows significant overlap with classic features of ARCL2 (also known as Debré-type cutis laxa), leading to the suggestion that WSS and ARCL2 are variable manifestations of the same disorder. The clinical spectrum in WSS also closely resembles that of geroderma osteodysplastica (GO) and to some extent that of De Barsy syndrome (DBS; see these terms). ## Etiology Although the etiology in some patients remains unknown, mutations in the ATP6V0A2 gene (12q24.31) have been identified both in patients with WSS and in those with autosomal recessive cutis laxa (ARCL) type 2 (see this term). Mutations in the PYCR1 gene (17q25.3) have recently been identified in patients with phenotypes (wrinkly skin, osteopenia and progeroid features) overlapping with ARCL2, GO and DBS. ## Diagnostic methods Histological findings are not pathognomonic for WSS (elastic fiber abnormalities may be mild or nonspecific) but may allow WSS to be distinguished from ARCL2 and ARCL1 (see this term). ## Genetic counseling WSS is transmitted in an autosomal recessive manner. ## Management and treatment Treatment is symptomatic. ## Prognosis Patients with WSS syndrome have a variable outcome. The prognosis depends on the underlying mutation and appears to be most benign in children with a mutation in the ATP6V0A2 gene. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Wrinkly skin syndrome

c0406587

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2834

{"gard": ["273"], "mesh": ["C536750"], "omim": ["278250"], "umls": ["C0406587"], "icd-10": ["Q82.8"], "synonyms": ["WSS", "Wrinkled skin syndrome"]}

Periventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means "out of place." In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles. Periventricular heterotopia usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Difficulty with reading and spelling (dyslexia) and movement problems have been reported in some people with periventricular heterotopia. Less commonly, individuals with periventricular heterotopia may have other features including more severe brain malformations, small head size (microcephaly), developmental delays, recurrent infections, blood vessel abnormalities, stomach problems, or lung disease. Periventricular heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels. ## Frequency Periventricular heterotopia is a rare condition. Its incidence is unknown. ## Causes In most cases, periventricular heterotopia is caused by mutations in the FLNA gene. This gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Certain mutations in the FLNA gene result in an impaired FLNA protein that cannot perform this function, disrupting the normal migration patterns of neurons during brain development. Periventricular heterotopia can also be caused by mutations in the ARFGEF2 gene. This gene provides instructions for making a protein that is involved in the movement (trafficking) of small sac-like structures (vesicles) within the cell. Vesicle trafficking is important in controlling the migration of neurons during the development of the brain. Mutations in the ARFGEF2 gene may disrupt this function, which could result in the abnormal neuronal migration seen in periventricular heterotopia. Researchers believe that mutations in the FLNA or ARFGEF2 genes may also result in weakening of the attachments (adhesion) between cells that form the lining of the ventricles. A weakened ventricular lining could allow some neurons to form clumps around the ventricles while others migrate normally to the exterior of the brain, as seen in periventricular heterotopia. In a few cases, periventricular heterotopia has been associated with abnormalities in chromosome 5. In each case, the affected individual had extra genetic material caused by an abnormal duplication of part of this chromosome. It is not known how this duplicated genetic material results in the signs and symptoms of periventricular heterotopia. ### Learn more about the genes and chromosome associated with Periventricular heterotopia * ARFGEF2 * FLNA * chromosome 5 Additional Information from NCBI Gene: * NEDD4L ## Inheritance Pattern Periventricular heterotopia can have different inheritance patterns. When this condition is caused by mutations in the FLNA gene, it is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In X-linked periventricular heterotopia, males experience much more severe symptoms of the disorder than females, and in most cases die before birth. In about 50 percent of cases of X-linked periventricular heterotopia, an affected person inherits the mutation from a mother who is also affected. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. Periventricular heterotopia caused by mutations in the ARFGEF2 gene is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Individuals with periventricular heterotopia in whom ARFGEF2 gene mutations have been identified have a severe form of the disorder, including microcephaly, severe developmental delay, and seizures beginning in infancy. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Periventricular heterotopia

c1842563

medlineplus

https://medlineplus.gov/genetics/condition/periventricular-heterotopia/

{"gard": ["12724"], "mesh": ["C564292"], "omim": ["608097", "300049", "608098", "617201"], "synonyms": []}

Dopamine-responsive dystonia Other namesSegawa syndrome, Segawa's disease, Segawa's dystonia, hereditary progressive dystonia with diurnal fluctuation SpecialtyNeurology, medical genetics Dopamine-responsive dystonia (DRD) also known as Segawa syndrome (SS), is a genetic movement disorder which usually manifests itself during early childhood at around ages 5–8 years (variable start age). Characteristic symptoms are increased muscle tone (dystonia, such as clubfoot) and Parkinsonian features, typically absent in the morning or after rest but worsening during the day and with exertion. Children with dopamine-responsive dystonia are often misdiagnosed as having cerebral palsy. The disorder responds well to treatment with levodopa. ## Contents * 1 Signs and symptoms * 2 Genetics * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 Research * 7 History * 8 References * 9 External links ## Signs and symptoms[edit] The disease typically starts in one limb, typically one leg. Progressive dystonia results in clubfoot and tiptoe walking. The symptoms can spread to all four limbs around age 18, after which progression slows and eventually symptoms reach a plateau. There can be regression in developmental milestones (both motor and mental skills) and failure to thrive in the absence of treatment. In addition, dopamine-responsive dystonia is typically characterized by signs of parkinsonism that may be relatively subtle. Such signs may include slowness of movement (bradykinesia), tremors, stiffness and resistance to movement (rigidity), balance difficulties, and postural instability. Approximately 25 percent also have abnormally exaggerated reflex responses (hyperreflexia), particularly in the legs. These symptoms can result in a presentation that is similar in appearance to that of Parkinson's disease. Many patients experience improvement with sleep, are relatively free of symptoms in the morning, and develop increasingly severe symptoms as the day progresses (i.e., diurnal fluctuation). Accordingly, this disorder has sometimes been referred to as "progressive hereditary dystonia with diurnal fluctuations." Yet some people with dopamine-responsive dystonia do not experience such diurnal fluctuations, causing many researchers to prefer other disease terms. Other symptoms - footwear * excessive wear at toes, but little wear on heels, thus replacement of shoes every college term/semester. Other symptoms - handwriting * near normal handwriting at infants/kindergarten (ages 3–5 school) years. * poor handwriting at pre-teens (ages 8–11 school) years. * very poor (worse) handwriting during teen (qv GCSE/A level-public exams) years. * bad handwriting (worsening) during post-teen (qv university exams) years. * very bad handwriting (still worsening) during adult (qv post-graduate exams) years. * worsening pattern of sloppy handwriting best observed by school teachers via termly reports. * child sufferer displays unhappy childhood facial expressions (possibly depression). ## Genetics[edit] Autosomal dominant and autosomal recessive forms of the disease have been reported. Mutations in several genes have been shown to cause dopamine-responsive dystonia. The precursor of the neurotransmitter dopamine, L-dopa, is synthesised from tyrosine by the enzyme tyrosine hydroxylase and utilises tetrahydrobiopterin (BH4) as a cofactor. A mutation in the gene GCH1, which encodes the enzyme GTP cyclohydrolase I, disrupts the production of BH4, decreasing dopamine levels (hypodopaminergia). This results in autosomal-dominant dopamine-responsive dystonia . Mutations in the genes for tyrosine hydroxylase and sepiapterin reductase result in autosomal-recessive forms of the disease. When the latter enzyme is affected, the condition tends to be more severe. The activity of dopaminergic neurons in the nigrostriatal pathway normally peaks during the morning and also decreases with age until after age 20, which explains why the symptoms worsen during the course of the day and with increasing age until the third decade of life. ## Diagnosis[edit] Due to the condition's rarity, it is frequently misdiagnosed, often as cerebral palsy. This results in patients often living their entire childhood with the condition untreated. The diagnosis of dopamine-responsive dystonia can be made from a typical history, a trial of dopamine medications, and genetic testing. Not all patients show mutations in the GCH1 gene (GTP cyclohydrolase I), which makes genetic testing imperfect. Sometimes a lumbar puncture is performed to measure concentrations of biopterin and neopterin, which can help determine the exact form of dopamine-responsive movement disorder: early onset parkinsonism (reduced biopterin and normal neopterin), GTP cyclohydrolase I deficiency (both decreased) and tyrosine hydroxylase deficiency (both normal). In approximately half of cases, a phenylalanine loading test can be used to show decreased conversion from the amino acid phenylalanine to tyrosine. This process uses BH4 as a cofactor. During a sleep study (polysomnography), decreased twitching may be noticed during REM sleep. An MRI scan of the brain can be used to look for conditions that can mimic dopamine-responsive dystonia (for example, metal deposition in the basal ganglia can indicate Wilson's disease or pantothenate kinase-associated neurodegeneration). Nuclear imaging of the brain using positron emission tomography (PET scan) shows a normal radiolabelled dopamine uptake in dopamine-responsive dystonia, contrary to the decreased uptake in Parkinson's disease. Other differential diagnoses include metabolic disorders (such as GM2 gangliosidosis, phenylketonuria, hypothyroidism, Leigh disease) primarily dystonic juvenile parkinsonism, autosomal recessive early onset parkinsonism with diurnal fluctuation, early onset idiopathic parkinsonism, focal dystonias, dystonia musculorum deformans and dyspeptic dystonia with hiatal hernia. Diagnosis - main * typically referral by GP to specialist Neurological Hospital e.g. National Hospital in London. * very hard to diagnose as condition is dynamic w.r.t. time-of-day AND dynamic w.r.t. age of patient. * correct diagnosis only made by a consultant neurologist with a complete 24-hour day-cycle observation (with video/film) at a hospital, i.e., morning (day1)->noon->afternoon->evening->late-night->sleep->morning (day2). * patient with suspected dopamine-responsive dystonia required to walk in around hospital in front of Neuro'-consultant at selected daytime intervals to observe worsening walking pattern coincident with increased muscle tension in limbs. * throughout the day, reducing leg-gait, thus shoe heels catching one another. * diurnal affect of condition: morning (fresh/energetic), lunch (stiff limbs), afternoon (very stiff limbs), evening (limbs worsening), bedtime (limbs near frozen). * muscle tension in thighs/arms: morning (normal), lunch (abnormal), afternoon (very abnormal), evening (bad), bedtime (frozen solid). Diagnosis - additional * lack of self-esteem at school/college/university -> eating disorders in youth thus weight gains. * lack of energy during late-daytime (teens/adult) -> compensate by over-eating. ## Treatment[edit] In those with dopamine-responsive dystonia, symptoms typically dramatically improve with low-dose administration of levodopa, which is a biochemically significant metabolite of the amino acid phenylalanine, as well as a biological precursor of the catecholamine dopamine, a neurotransmitter. (Neurotransmitters are naturally produced molecules that may be sequestered following the propagation of an action potential down a nerve towards the axon terminal, which in turn may cross the synaptic junction between neurons, enabling neurons to communicate in a variety of ways.) Low-dose L-dopa usually results in near-complete or total reversal of all associated symptoms for these patients. In addition, the effectiveness of such therapy is typically long term, without the complications that often occur for those with Parkinson's disease who undergo L-dopa treatment. Thus, most experts indicate that this disorder is most appropriately known as dopa-responsive dystonia. No data are available on mortality associated with dopamine-responsive dystonia, but patients surviving beyond the fifth decade with treatment have been reported. However, in severe, early autosomal recessive forms of the disease, patients have been known to pass away during childhood. Girls seem to be somewhat more commonly affected. The disease less commonly begins during puberty or after age 20, and very rarely, cases in older adults have been reported. Due to commonly being misdiagnosed, it is common for the disease to remain untreated. When left untreated, patients often need Achilles' tendon surgery by the age of 21. They will also struggle with walking, an ability that will degrade throughout the day. Power napping can provide temporary relief in untreated patients. It also impairs development into adulthood, reduces balance, and reduces calf muscle development. Socially, it can result in depression, lack of social skills, and inability to find employment. ## Epidemiology[edit] This condition is very rare, only affecting one in two million people. It is more common in females than in males. There are several hundred cases in the United States, 25 known cases in the United Kingdom, and less than that in Australia and New Zealand. ## Research[edit] Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders.[1] ## History[edit] The disease is named after Dr. Masaya Segawa, who provided an early clinical description.[2] ## References[edit] 1. ^ "Patient registry". 2. ^ Segawa M, Hosaka A, Miyagawa F, Nomura Y, Imai H (1976). "Hereditary progressive dystonia with marked diurnal fluctuation". Advances in Neurology. 14: 215–33. PMID 945938. ## External links[edit] * GeneReview/NCBI/NIH/UW entry on GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia * GeneReview/NCBI/NIH/UW entry on Tyrosine Hydroxylase Deficiency Classification D * ICD-10: G24.1 * OMIM: 600225 * MeSH: C538007 External resources * eMedicine: neuro/168 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Dopamine-responsive dystonia

c1851920

wikipedia

https://en.wikipedia.org/wiki/Dopamine-responsive_dystonia

{"gard": ["9817"], "mesh": ["C538007"], "umls": ["C1851920"], "icd-10": ["G24.1"], "orphanet": ["255"], "wikidata": ["Q689777"]}

A rare, genetic, non-severe combined immunodeficiency disease characterized by immunodeficiency (manifested by recurrent and/or severe bacterial and viral infections), destructive noninfectious granulomas involving skin, mucosa and internal organs, and various autoimmune manifestations (including cytopenias, vitiligo, psoriasis, myasthenia gravis, enteropathy). Immunophenotypically, T-cell and B-cell lymphopenia, hypogammaglobulinemia, abnormal specific antibody production and impaired T-cell function are observed. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Combined immunodeficiency with granulomatosis

c2673536

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157949

{"mesh": ["C567115"], "omim": ["233650"], "umls": ["C2673536"], "icd-10": ["D81.1"], "synonyms": ["CID due to RAG 1/2 deficiency", "Combined immunodeficiency due to RAG 1/2 deficiency"]}

A number sign (#) is used with this entry because of evidence that presynaptic congenital myasthenic syndrome-7 (CMS7) is caused by heterozygous mutation in the SYT2 gene (600104) on chromosome 1q32. Description Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. CMS7 is an autosomal dominant CMS resulting from a presynaptic defect; patients have onset of symptoms in early childhood (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). Clinical Features Herrmann et al. (2014) reported 2 unrelated multigenerational families with congenital myasthenic syndrome. The first family was from the United States and contained 4 patients who presented in early childhood with foot deformities, including pes cavus and hammertoes. They had variable proximal and distal limb weakness, muscle fatigue that improved with rest, mild gait difficulties, and reduced deep tendon reflexes that could be elicited after brief exercise. Two of 4 individuals also had hearing loss, which was associated with vertigo in 1. Electrophysiologic studies showed reduced compound muscle action potential (CMAP) amplitudes, consistent with presynaptic dysfunction of the NMJ, and marked CMAP facilitation following brief exercise. The second family was from the United Kingdom and contained 6 affected individuals. The patients presented in early childhood with foot deformities as well as congenital hip dislocation. There was distal weakness and atrophy of the lower extremities and absent deep tendon reflexes. Electromyography showed a slight reinnervation of distal muscles, consistent with a motor neuropathy. Sensory nerve conduction studies were normal in all individuals from both families. Whittaker et al. (2015) reported the electrophysiologic findings of affected members of the 2 families with CMS9 reported by Herrmann et al. (2014). Repetitive nerve stimulation resulted in large decrements of the motor amplitude, consistent with myasthenic syndrome, and maximum voluntary contraction resulted in posttetanic potentiation lasting up to 60 minutes. These findings were consistent with a presynaptic defect at the neuromuscular junction. Two patients in 1 family showed no therapeutic response to pyridostigmine, but showed slight improvement in exercise tolerance with 3,4-diaminopyridine. The improvement with 3,4-diaminopyridine was confirmed by single-fiber EMG studies on 1 of the patients. Inheritance The transmission pattern of presynaptic congenital myasthenic syndrome in the families reported by Herrmann et al. (2014) was consistent with autosomal dominant inheritance. Molecular Genetics In 2 unrelated Caucasian families with CMS7, Herrmann et al. (2014) identified 2 different heterozygous missense mutations in the SYT2 gene (D307A, 600104.0001 and P308L, 600104.0002). The mutations, which were found by whole-exome sequencing, segregated with the disorder in both families. Transfection of D362A (the Drosophila mutation corresponding to human D307A) in the Drosophila ortholog Dsyt1 was unable to rescue neurotransmitter release defects in Dsyt1-null flies. Flies transfected with the mutation lacked synchronous neurotransmitter release at the NMJ, showed enhanced asynchronous release, and exhibited increased spontaneous fusion rates with a strong dominant-negative effect. The findings indicated that the D362A mutation abolished the ability of the protein to support calcium-triggered neurotransmitter release in peripheral motor nerve terminals. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss (2 patients) SKELETAL Pelvis \- Hip dislocation, congenital (1 family) MUSCLE, SOFT TISSUES \- Distal muscle weakness (lower limbs more severely affected than upper limbs) \- Proximal muscle weakness (in some patients) \- Easy fatigability with exercise \- Gait abnormalities \- Impaired toe-walking \- Impaired heel-walking \- Muscle atrophy (in some patients) \- Low-amplitude compound muscle action potential (CMAP) \- Postexercise CMAP amplitude facilitation \- Presynaptic defect at the neuromuscular junction \- Evidence of reinnervation seen on EMG (1 family) NEUROLOGIC Peripheral Nervous System \- Hyporeflexia \- Areflexia \- Motor neuropathy (1 family) MISCELLANEOUS \- Two unrelated families have been reported (last curated September 2014) \- Onset in early childhood MOLECULAR BASIS \- Caused by mutation in the synaptotagmin-2 gene (SYT2, 600104.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MYASTHENIC SYNDROME, CONGENITAL, 7, PRESYNAPTIC

c0751884

omim

https://www.omim.org/entry/616040

{"doid": ["0110659"], "mesh": ["D020294"], "omim": ["616040"], "orphanet": ["98914", "590"], "synonyms": ["Alternative titles", "MYASTHENIC SYNDROME, PRESYNAPTIC, CONGENITAL, WITH OR WITHOUT MOTOR NEUROPATHY"], "genereviews": ["NBK1168"]}

Rare genetic disorder of the white matter of the brain Alexander disease Brain of a 4-year-old boy with Alexander disease showing macroencephaly and periventricular leukomalacia (note brownish discoloration around the cerebral ventricles) SpecialtyEndocrinology, neurology Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first 2 years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size and seizures. The juvenile form of Alexander disease has an onset between the ages of 2 and 13 years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder. According to the National Institute of Neurological Disorders and Stroke, the destruction of white matter is accompanied by the formation of Rosenthal fibers—abnormal clumps of protein that accumulate in astrocytes in the brain. The disease occurs in both males and females, and no ethnic, racial, geographic or cultural/economic differences are seen in its distribution. Alexander disease is a progressive and often fatal disease.[1] ## Contents * 1 Presentation * 2 Cause * 3 Pathology * 4 Diagnosis * 5 Treatment * 6 Prognosis * 7 Prevalence * 8 See also * 9 References * 10 External links ## Presentation[edit] Delays in development of some physical, psychological and behavioral skills; progressive enlargement of the head (macrocephaly), seizures, spasticity, and in some cases also hydrocephalus, idiopathic intracranial hypertension, and dementia.[2] ## Cause[edit] Alexander disease is a genetic disorder affecting the midbrain and cerebellum of the central nervous system. It is caused by mutations in the gene for glial fibrillary acidic protein (GFAP)[3][4][5] that maps to chromosome 17q21\. It is inherited in an autosomal recessive manner, such that the child of a parent with the disease has a 50% chance of inheriting the condition, if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations.[2] Alexander disease belongs to leukodystrophies, a group of diseases that affect the growth or development of the myelin sheath. The destruction of white matter in the brain is accompanied by the formation of fibrous, eosinophilic deposits known as Rosenthal fibers.[2][6][7] Rosenthal fibers appear not to be present in healthy people,[6][8] but occur in specific diseases, like some forms of cancer, Alzheimer’s, Parkinson’s, Huntington’s, and ALS.[6][8][9] The Rosenthal fibers found in Alexander disease do not share the distribution or concentration of other diseases and disorders.[6] ## Pathology[edit] Alexander disease causes the gradual loss of bodily functions and the ability to talk. It also causes an overload of long-chain fatty acids in the brain, which destroy the myelin sheath. The cause of Alexander disease is a mutation in the gene encoding GFAP.[2][6][3][4][10][9][excessive citations] A CT scan shows: * Decreased density of white matter * Frontal lobe predominance * Dilated lateral ventricles may present ## Diagnosis[edit] Detecting the signs of Alexander disease is possible with magnetic resonance imaging (MRI), which looks for specific changes in the brain that may be tell-tale signs for the disease.[11][12] It is even possible to detect adult-onset Alexander disease with MRI.[10] Alexander disease may also be revealed by genetic testing for its known cause.[13][14] A rough diagnosis may also be made through revealing of clinical symptoms, including enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.[8] ## Treatment[edit] No cure or standard procedure for treatment is known, although a University of Wisconsin study shows promise with gene editing of the astrocytes.[2][6][9] A bone marrow transplant has been attempted on a child, but it made no improvement.[15][16] Hydrocephalus may be seen in younger patients and can be relieved with surgery or by implanting a shunt to relieve pressure.[17] ## Prognosis[edit] The prognosis is generally poor. With early onset, death usually occurs within 10 years from the onset of symptoms. Individuals with the infantile form usually die before the age of seven.[18] Usually, the later the disease occurs, the slower its course.[2][6] ## Prevalence[edit] Its occurrence is very rare. The infantile form occurs from birth to 2 years of age.[5] The average duration of the infantile form is usually about 3 years. Onset of the juvenile form presents between 2 and 12 years of age.[5] Duration of this form is in most cases about 6 years. The adult form occurs after 12 years.[5] In younger patients, seizures, megalencephaly, developmental delay, and spasticity are usually present. Neonatal onset is also reported.[19] Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms and spasticity predominate. Symptoms of the adult form may also resemble multiple sclerosis.[2] No more than 500 cases have been reported.[2] ## See also[edit] * The Myelin Project * The Stennis Foundation ## References[edit] 1. ^ "Alexander Disease Information Page". National Institute of Neurological Disorders and Stroke. 2018. This article incorporates text from this source, which is in the public domain. 2. ^ a b c d e f g h GeneReviews/NCBI/NIH/UW entry on Alexander disease 3. ^ a b Li R, Messing A, Goldman JE, Brenner M (2002). "GFAP mutations in Alexander disease". Int. J. Dev. Neurosci. 20 (3–5): 259–68. doi:10.1016/s0736-5748(02)00019-9. PMID 12175861. S2CID 13541342. 4. ^ a b Quinlan RA, Brenner M, Goldman JE, Messing A (June 2007). "GFAP and its role in Alexander disease". Exp. Cell Res. 313 (10): 2077–87. doi:10.1016/j.yexcr.2007.04.004. PMC 2702672. PMID 17498694. 5. ^ a b c d Messing A, Brenner M, Feany MB, Nedergaard M, Goldman JE (April 2012). "Alexander disease". J. Neurosci. 32 (15): 5017–23. doi:10.1523/JNEUROSCI.5384-11.2012. PMC 3336214. PMID 22496548. 6. ^ a b c d e f g alexander_disease at NINDS 7. ^ "Cause of brain disease found" -BBC News 8. ^ a b c "Archived copy". Archived from the original on 2010-04-28. Retrieved 2010-06-14.CS1 maint: archived copy as title (link) 9. ^ a b c "Mutation in common protein triggers tangles, chaos inside brain cells". news.wisc.edu. Retrieved 2018-11-16. 10. ^ a b Farina L, Pareyson D, Minati L, et al. (June 2008). "Can MR imaging diagnose adult-onset Alexander disease?". AJNR Am J Neuroradiol. 29 (6): 1190–6. doi:10.3174/ajnr.A1060. PMID 18388212. 11. ^ Labauge P (June 2009). "Magnetic resonance findings in leucodystrophies and MS". Int MS J. 16 (2): 47–56. PMID 19671368. 12. ^ van der Knaap MS, Naidu S, Breiter SN, et al. (March 2001). "Alexander disease: diagnosis with MR imaging". AJNR Am J Neuroradiol. 22 (3): 541–52. PMID 11237983. 13. ^ Johnson AB (2002). "Alexander disease: a review and the gene". Int. J. Dev. Neurosci. 20 (3–5): 391–4. doi:10.1016/S0736-5748(02)00045-X. PMID 12175878. S2CID 12408421. 14. ^ Sawaishi, Y (August 2009). "Review of Alexander disease: beyond the classical concept of leukodystrophy". Brain Dev. 31 (7): 493–8. doi:10.1016/j.braindev.2009.03.006. PMID 19386454. S2CID 206312570. 15. ^ Staba MJ, Goldman S, Johnson FL, Huttenlocher PR (August 1997). "Allogeneic bone marrow transplantation for Alexander's disease". Bone Marrow Transplant. 20 (3): 247–9. doi:10.1038/sj.bmt.1700871. PMID 9257894. 16. ^ Messing A, LaPash Daniels CM, Hagemann TL (October 2010). "Strategies for treatment in Alexander disease". Neurotherapeutics. 7 (4): 507–15. doi:10.1016/j.nurt.2010.05.013. PMC 2948554. PMID 20880512. 17. ^ "Alexander Disease - United Leukodystrophy Foundation United Leukodystrophy Foundation". ulf.org. Retrieved 2016-11-08. 18. ^ "Alexander Disease Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". www.ninds.nih.gov. Archived from the original on 2012-05-14. Retrieved 2016-11-03. 19. ^ Singh N, Bixby C, Etienne D, Tubbs RS, Loukas M (December 2012). "Alexander's disease: reassessment of a neonatal form". Childs Nerv Syst. 28 (12): 2029–31. doi:10.1007/s00381-012-1868-8. PMID 22890470. S2CID 5851209. ## External links[edit] Wikimedia Commons has media related to Alexander disease. * OMIM entries on Alexander disease * Infantile-onset Alexander disease in a child with long-term follow-up by serial magnetic resonance imaging: a case report * Alexander Disease: New Insights From Genetics Classification D * ICD-10: E75.2 * ICD-9-CM: 331.89 * OMIM: 203450 137780 137780 203450 * MeSH: D038261 External resources * GeneReviews: Alexander disease * Orphanet: 58 * v * t * e Multiple sclerosis and other demyelinating diseases of the central nervous system Signs and symptoms * Ataxia * Depression * Diplopia * Dysarthria * Dysphagia * Fatigue * Incontinence * Nystagmus * Optic neuritis * Pain * Uhthoff's phenomenon Investigations and diagnosis * Multiple sclerosis diagnosis * McDonald criteria * Poser criteria * Clinical * Clinically isolated syndrome * Expanded Disability Status Scale * Serological and CSF * Oligoclonal bands * Radiological * Radiologically isolated syndrome * Lesional demyelinations of the central nervous system * Dawson's fingers Approved[by whom?] treatment * Management of multiple sclerosis * Alemtuzumab * Cladribine * Dimethyl fumarate * Fingolimod * Glatiramer acetate * Interferon beta-1a * Interferon beta-1b * Mitoxantrone * Natalizumab * Ocrelizumab * Ozanimod * Siponimod * Teriflunomide Other treatments * Former * Daclizumab * Multiple sclerosis research Demyleinating diseases Autoimmune * Multiple sclerosis * Neuromyelitis optica * Diffuse myelinoclastic sclerosis Inflammatory * Acute disseminated encephalomyelitis * MOG antibody disease * Balo concentric sclerosis * Marburg acute multiple sclerosis * Neuromyelitis optica * Diffuse myelinoclastic sclerosis * Tumefactive multiple sclerosis * Experimental autoimmune encephalomyelitis Hereditary * Adrenoleukodystrophy * Alexander disease * Canavan disease * Krabbe disease * Metachromatic leukodystrophy * Pelizaeus–Merzbacher disease * Leukoencephalopathy with vanishing white matter * Megalencephalic leukoencephalopathy with subcortical cysts * CAMFAK syndrome Other * Central pontine myelinolysis * Marchiafava–Bignami disease * Mitochondrial DNA depletion syndrome Other * List of multiple sclerosis organizations * List of people with multiple sclerosis * Multiple sclerosis drug pipeline * Pathophysiology * v * t * e Cytoskeletal defects Microfilaments Myofilament Actin * Hypertrophic cardiomyopathy 11 * Dilated cardiomyopathy 1AA * DFNA20 * Nemaline myopathy 3 Myosin * Elejalde syndrome * Hypertrophic cardiomyopathy 1, 8, 10 * Usher syndrome 1B * Freeman–Sheldon syndrome * DFN A3, 4, 11, 17, 22; B2, 30, 37, 48 * May–Hegglin anomaly Troponin * Hypertrophic cardiomyopathy 7, 2 * Nemaline myopathy 4, 5 Tropomyosin * Hypertrophic cardiomyopathy 3 * Nemaline myopathy 1 Titin * Hypertrophic cardiomyopathy 9 Other * Fibrillin * Marfan syndrome * Weill–Marchesani syndrome * Filamin * FG syndrome 2 * Boomerang dysplasia * Larsen syndrome * Terminal osseous dysplasia with pigmentary defects IF 1/2 * Keratinopathy (keratosis, keratoderma, hyperkeratosis): KRT1 * Striate palmoplantar keratoderma 3 * Epidermolytic hyperkeratosis * IHCM * KRT2E (Ichthyosis bullosa of Siemens) * KRT3 (Meesmann juvenile epithelial corneal dystrophy) * KRT4 (White sponge nevus) * KRT5 (Epidermolysis bullosa simplex) * KRT8 (Familial cirrhosis) * KRT10 (Epidermolytic hyperkeratosis) * KRT12 (Meesmann juvenile epithelial corneal dystrophy) * KRT13 (White sponge nevus) * KRT14 (Epidermolysis bullosa simplex) * KRT17 (Steatocystoma multiplex) * KRT18 (Familial cirrhosis) * KRT81/KRT83/KRT86 (Monilethrix) * Naegeli–Franceschetti–Jadassohn syndrome * Reticular pigmented anomaly of the flexures 3 * Desmin: Desmin-related myofibrillar myopathy * Dilated cardiomyopathy 1I * GFAP: Alexander disease * Peripherin: Amyotrophic lateral sclerosis 4 * Neurofilament: Parkinson's disease * Charcot–Marie–Tooth disease 1F, 2E * Amyotrophic lateral sclerosis 5 * Laminopathy: LMNA * Mandibuloacral dysplasia * Dunnigan Familial partial lipodystrophy * Emery–Dreifuss muscular dystrophy 2 * Limb-girdle muscular dystrophy 1B * Charcot–Marie–Tooth disease 2B1 * LMNB * Barraquer–Simons syndrome * LEMD3 * Buschke–Ollendorff syndrome * Osteopoikilosis * LBR * Pelger–Huet anomaly * Hydrops-ectopic calcification-moth-eaten skeletal dysplasia Microtubules Kinesin * Charcot–Marie–Tooth disease 2A * Hereditary spastic paraplegia 10 Dynein * Primary ciliary dyskinesia * Short rib-polydactyly syndrome 3 * Asphyxiating thoracic dysplasia 3 Other * Tauopathy * Cavernous venous malformation Membrane * Spectrin: Spinocerebellar ataxia 5 * Hereditary spherocytosis 2, 3 * Hereditary elliptocytosis 2, 3 Ankyrin: Long QT syndrome 4 * Hereditary spherocytosis 1 Catenin * APC * Gardner's syndrome * Familial adenomatous polyposis * plakoglobin (Naxos syndrome) * GAN (Giant axonal neuropathy) Other * desmoplakin: Striate palmoplantar keratoderma 2 * Carvajal syndrome * Arrhythmogenic right ventricular dysplasia 8 * plectin: Epidermolysis bullosa simplex with muscular dystrophy * Epidermolysis bullosa simplex of Ogna * plakophilin: Skin fragility syndrome * Arrhythmogenic right ventricular dysplasia 9 * centrosome: PCNT (Microcephalic osteodysplastic primordial dwarfism type II) Related topics: Cytoskeletal proteins *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Alexander disease

c0270726

wikipedia

https://en.wikipedia.org/wiki/Alexander_disease

{"gard": ["5774"], "mesh": ["D038261"], "umls": ["C0270726"], "icd-9": ["331.89"], "icd-10": ["E75.2"], "orphanet": ["58"], "wikidata": ["Q567820"]}

Lisch epithelial corneal dystrophy Other namesBand-shaped and whorled microcystic dystrophy of the corneal epithelium X-linked recessive is the inheritance pattern of this condition SpecialtyOphthalmology Lisch epithelial corneal dystrophy (LECD), also known as band-shaped and whorled microcystic dystrophy of the corneal epithelium, is a rare form of corneal dystrophy first described in 1992 by Lisch et al.[1] In one study it was linked to chromosomal region Xp22.3, with as yet unknown candidate genes.[2] The main features of this disease are bilateral or unilateral gray band-shaped and feathery opacities. They sometimes take on a form of a whirlpool, repeating the known pattern of corneal epithelium renewal. Abrasion of the epithelium in 3 patients brought only temporary relief, with abnormal epithelium regrowth in several months. Epithelial cells in the zones of opacity were shown to have diffuse cytoplasmic vacuoles with as yet unestablished content. ## References[edit] 1. ^ Lisch W, Steuhl KP, Lisch C, Weidle EG, Emmig CT, Cohen KL, Perry HD (July 1992). "A new, band-shaped and whorled microcystic dystrophy of the corneal epithelium". Am. J. Ophthalmol. 114 (1): 35–44. doi:10.1016/S0002-9394(14)77410-0. PMID 1621784. 2. ^ Lisch W, Büttner A, Oeffner F, Böddeker I, Engel H, Lisch C, Ziegler A, Grzeschik K (October 2000). "Lisch corneal dystrophy is genetically distinct from Meesmann corneal dystrophy and maps to xp22.3". Am. J. Ophthalmol. 130 (4): 461–8. doi:10.1016/S0002-9394(00)00494-3. PMID 11024418. ## External links[edit] Classification D * ICD-10: H18.5 * OMIM: 300778 * MeSH: C567588 C567588, C567588 External resources * Orphanet: 98955 * v * t * e Types of corneal dystrophy Epithelial and subepithelial * Epithelial basement membrane dystrophy * Gelatinous drop-like corneal dystrophy * Lisch epithelial corneal dystrophy * Meesmann corneal dystrophy * Subepithelial mucinous corneal dystrophy Bowman's membrane * Reis–Bucklers corneal dystrophy * Thiel-Behnke dystrophy Stroma * Congenital stromal corneal dystrophy * Fleck corneal dystrophy * Granular corneal dystrophy * Lattice corneal dystrophy * Macular corneal dystrophy * Posterior amorphous corneal dystrophy * Schnyder crystalline corneal dystrophy Descemet's membrane and endothelial * Congenital hereditary endothelial dystrophy * Fuchs' dystrophy * Posterior polymorphous corneal dystrophy * X-linked endothelial corneal dystrophy This article about an ophthalmic disease is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Lisch epithelial corneal dystrophy

c2749050

wikipedia

https://en.wikipedia.org/wiki/Lisch_epithelial_corneal_dystrophy

{"mesh": ["C567588"], "umls": ["C2749050"], "orphanet": ["98955"], "wikidata": ["Q4162391"]}

Immune reconstitution inflammatory syndrome SpecialtyImmunology Immune reconstitution inflammatory syndrome (IRIS) is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.[1] ## Contents * 1 In HIV infection and immunosuppression * 2 In cryptococcal meningitis * 3 In bats recovering from white-nose syndrome * 4 See also * 5 References * 6 Further reading * 7 External links ## In HIV infection and immunosuppression[edit] The suppression of CD4 T cells by HIV (or by immunosuppressive drugs) causes a decrease in the body's normal response to certain infections. Not only does this make it more difficult to fight the infection, it may mean that a level of infection that would normally produce symptoms is instead undetected (subclinical infection). If the CD4 count rapidly increases (due to effective treatment of HIV, or removal of other causes of immunosuppression), a sudden increase in the inflammatory response produces nonspecific symptoms such as fever, and in some cases a worsening of damage to the infected tissue.[citation needed] There are two common IRIS scenarios. The first is the “unmasking” of an occult opportunistic infection. The second is the “paradoxical” symptomatic relapse of a prior infection despite microbiologic treatment success. Often in paradoxical IRIS, microbiologic cultures are sterile. In either scenario, there is hypothesized reconstitution of antigen-specific T cell-mediated immunity with activation of the immune system following HIV therapy against persisting antigen, whether present as intact organisms, dead organisms, or debris.[2] Though these symptoms can be dangerous, they also indicate that the body may now have a better chance to defeat the infection. The best treatment for this condition is unknown. In paradoxical IRIS reactions, the events will usually spontaneously get better with time without any additional therapy. In unmasking IRIS, the most common treatment is to administer antibiotic or antiviral drugs against the infectious organism. In some severe cases, anti-inflammatory medications, such as corticosteroids are needed to suppress inflammation until the infection has been eliminated.[citation needed] Infections most commonly associated with IRIS include Mycobacterium tuberculosis and cryptococcal meningitis. Persons living with AIDS are more at risk for IRIS if they are starting HAART for the first time, or if they have recently been treated for an opportunistic infection (OI). It is generally advised that when patients have low initial CD4 T cell count and opportunistic infection at the time of their HIV diagnosis, they receive treatment to control the opportunistic infections before HAART is initiated approximately two weeks later. This is true for most OIs, except for OIs involving the central nervous system.[citation needed] ## In cryptococcal meningitis[edit] IRIS is particularly problematic in cryptococcal meningitis as IRIS is fairly common and can be fatal.[3] IRIS has been described in immunocompetent hosts who have meningitis caused by Cryptococcus gattii and Cryptococcus neoformans var. grubii, environmental fungi which often affect immunocompetent hosts. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.[citation needed] Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is typically sterile, and there is no increase in CSF cryptococcal antigen titer.[4] The increasing inflammation can cause brain injury or be fatal.[5][6][7] The general mechanism behind IRIS is increased inflammation as the recovering immune system recognizes the antigens of the fungus as immunosuppression is reversed. Cryptococcal IRIS has three phases: 1. before HAART, with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance; 2. during initial HAART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and 3. at IRIS, a cytokine storm with a predominant type-1 helper T-cell interferon-gamma response.[3][4][8] Three clinical predictors of cryptococcal-related paradoxical IRIS risk include:[citation needed] 1. lack of initial CSF pleocytosis (i.e. low CSF white blood cell count); 2. elevated C-reactive protein; 3. failure to sterilize the CSF before immune recovery. IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom Cryptococcus neoformans is the usual pathogen. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration. Steroids given to persons with anti-fungal treatment failure / cryptococcal relapse (in whom CSF cultures are not sterile) can be a fatal iatrogenic error.[9] ## In bats recovering from white-nose syndrome[edit] Bats recovering from white-nose syndrome (WNS) may be the first natural occurrence of IRIS, in a report released by the USGS.[10] WNS is typified by a cutaneous infection of the fungus Pseudogymnoascus destructans during hibernation, when the immune system is naturally suppressed to conserve energy through the winter. This study suggests that bats undergoing an intense inflammation at the site of infection after a return to euthermia is a form of IRIS.[11] ## See also[edit] * List of cutaneous conditions * Jarisch-Herxheimer reaction, another systemic inflammatory syndrome that arises after antimicrobial treatment ## References[edit] 1. ^ Shelburne, Samuel A; Visnegarwala, Fehmida; Darcourt, Jorge; Graviss, Edward A; Giordano, Thomas P; White, A Clinton; Hamill, Richard J (March 2005). "Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy". AIDS. 19 (4): 399–406. doi:10.1097/01.aids.0000161769.06158.8a. PMID 15750393. S2CID 2062992. 2. ^ Bohjanen, Paul R.; Boulware, David R. (2008). "HIV Immune Reconstitution Inflammatory Syndrome". Global HIV/AIDS Medicine. pp. 193–205. doi:10.1016/B978-1-4160-2882-6.50022-8. ISBN 978-1-4160-2882-6. 3. ^ a b Boulware, David R.; Meya, David B.; Bergemann, Tracy L.; Wiesner, Darin L.; Rhein, Joshua; Musubire, Abdu; Lee, Sarah J.; Kambugu, Andrew; Janoff, Edward N.; Bohjanen, Paul R. (21 December 2010). "Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study". PLOS Medicine. 7 (12): e1000384. doi:10.1371/journal.pmed.1000384. PMC 3014618. PMID 21253011. 4. ^ a b Boulware, David R.; Bonham, Shulamith C.; Meya, David B.; Wiesner, Darin L.; Park, Gregory S.; Kambugu, Andrew; Janoff, Edward N.; Bohjanen, Paul R. (15 September 2010). "Paucity of Initial Cerebrospinal Fluid Inflammation in Cryptococcal Meningitis Is Associated with Subsequent Immune Reconstitution Inflammatory Syndrome". The Journal of Infectious Diseases. 202 (6): 962–970. doi:10.1086/655785. PMC 2924457. PMID 20677939. 5. ^ Lane, M.; McBride, J.; Archer, J. (23 August 2004). "Steroid responsive late deterioration in Cryptococcus neoformans variety gattii meningitis". Neurology. 63 (4): 713–714. doi:10.1212/01.wnl.0000134677.29120.62. PMID 15326249. S2CID 42308361. 6. ^ Einsiedel, L.; Gordon, D. L.; Dyer, J. R. (15 October 2004). "Paradoxical Inflammatory Reaction during Treatment of Cryptococcus neoformans var. gattii Meningitis in an HIV-Seronegative Woman". Clinical Infectious Diseases. 39 (8): e78–e82. doi:10.1086/424746. PMID 15486830. 7. ^ Ecevit, Ismail Zafer; Clancy, Cornelius J.; Schmalfuss, Ilona M.; Nguyen, M. Hong (2006). "The Poor Prognosis of Central Nervous System Cryptococcosis among Nonimmunosuppressed Patients: A Call for Better Disease Recognition and Evaluation of Adjuncts to Antifungal Therapy". Clinical Infectious Diseases. 42 (10): 1443–1447. doi:10.1086/503570. JSTOR 4484756. PMID 16619158. 8. ^ Wiesner, Darin L.; Boulware, David R. (4 August 2011). "Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome (IRIS): Pathogenesis and its Clinical Implications". Current Fungal Infection Reports. 5 (4): 252–261. doi:10.1007/s12281-011-0064-8. PMC 3289516. PMID 22389746. 9. ^ Musubire, AK; Meya, BD; Mayanja-Kizza, H; Lukande, R; Wiesner, LD; Bohjanen, P; R Boulware, RD (2012). "Challenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings". African Health Sciences. 12 (2): 226–230. doi:10.4314/ahs.v12i2.23. PMC 3462548. PMID 23056032. 10. ^ "White-Nose Syndrome Bat Recovery May Present Challenges Similar to Those in Some Recovering AIDS Patients" (Press release). USGS. November 19, 2012. Retrieved February 22, 2020. 11. ^ Meteyer, Carol; Barber, Daniel; Mandl, Judith (2012-11-15). "Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome". Virulence. 3 (7): 583–588. doi:10.4161/viru.22330. PMC 3545935. PMID 23154286. ## Further reading[edit] * Bolognia, Jean; Schaffer, Julie V; Cerroni, Lorenzo, eds. (2018). "Immune Reconstitution Inflammatory Syndrome (IRIS)". Dermatology. p. 1378. ISBN 978-0-7020-6342-8. OCLC 1016978099. ## External links[edit] * "Immune Reconstitution Syndrome" at TheBody.com (by Nicholas Cheonis, Winter 2004/2005) *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy

Immune reconstitution inflammatory syndrome

c1619738

wikipedia

https://en.wikipedia.org/wiki/Immune_reconstitution_inflammatory_syndrome

{"mesh": ["D054019"], "wikidata": ["Q539986"]}

Luo et al. (1995) performed affected-sib-pair analyses in 104 Caucasian families to map genes predisposed to insulin-dependent diabetes mellitus (IDDM; see 222100). They observed linkage for D6S446 (maximum lod = 2.8) and for D6S264 (maximum lod = 2.0) on 6q25-q27. Together with a previously reported data set, linkage could be firmly established (maximum lod score = 3.4 for D6S264), and the disease locus was designated IDDM8. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy

DIABETES MELLITUS, INSULIN-DEPENDENT, 8

c1833218

omim

https://www.omim.org/entry/600883

{"mesh": ["C563433"], "omim": ["600883"], "synonyms": ["Alternative titles", "INSULIN-DEPENDENT DIABETES MELLITUS 8"]}

A number sign (#) is used with this entry because transient neonatal diabetes mellitus-1 (TNDM1; '6q diabetes') is caused by overexpression of the paternal allele of the imprinted locus at chromosome 6q24, which contains only 2 expressed genes, PLAGL1 (603044) and HYMAI (606546). Some TNMD1 cases are caused by homozygous or compound heterozygous mutations in the ZFP57 gene (612192) at chromosome 6p22, which affects the methylation status of the imprinted locus at 6q24. Description Neonatal diabetes mellitus (NDM), defined as insulin-requiring hyperglycemia within the first month of life, is a rare entity, with an estimated incidence of 1 in 400,000 neonates (Shield, 2000). In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes (606176). In a significant number of patients with transient neonatal diabetes mellitus, type II diabetes appears later in life (Arthur et al., 1997). The major cause of transient neonatal diabetes (TND) is aberrant expression of imprinted genes at chromosome 6q24, associated in 20% of cases with DNA hypomethylation at the TND differentially methylated region (DMR), which lies within the imprinted promoter of the PLAGL1 gene (603044; Mackay et al., 2005). Over 50% of individuals with TND and hypomethylation at 6q24 also show mosaic DNA hypomethylation at other imprinted loci throughout the genome and a range of additional clinical features. ### Genetic Heterogeneity of Transient Neonatal Diabetes TNDM2 (610374) is caused by mutation in the ABCC8 gene (600509) on chromosome 11p15.1. TNDM3 (610582) is caused by mutation in the KCNJ11 gene (600937), also located on 11p15.1. Clinical Features Temple et al. (1996) reviewed the manifestations of transient neonatal diabetes mellitus and the evidence for an imprinted, paternally expressed gene on chromosome 6q22-q23. They reported that TNDM occurs with a frequency of approximately 1 in 500,000 births. Patients are born with intrauterine growth retardation and present within the first 6 weeks of life with severe failure to thrive, hyperglycemia, and dehydration. Temple et al. (1996) noted that there is evidence for failure of insulin (176730) production in response to glucose feeding and that insulin therapy is usually required. The condition usually resolves within the first 6 months of life. However, there is a predisposition toward type 2 (insulin resistant) diabetes (see 601283) later in life. Christian et al. (1999) reported 2 patients who presented at birth with neonatal diabetes mellitus (NDM): one with paternal uniparental disomy for chromosome 6 and one with normal, biparental inheritance. The first child presented with low birth weight, macroglossia, hypertelorism, and clubfoot in addition to NDM. In this patient hyperglycemia was transient, and insulin treatment was discontinued at 4 months of age. The second child also presented with low birth weight but was normal in appearance, and insulin dependence continued after 5 years. Genetic analysis with polymorphic DNA markers for chromosome 6 indicated the presence of paternal uniparental disomy (UPD6) in the first case and normal, biparental inheritance in the second case. Christian et al. (1999) found reports of 8 previous cases of UPD6 of which 6 showed NDM. Three cases with paternal UPD6 also included additional anomalies, such as macroglossia, not usually associated with NDM. Christian et al. (1999) suggested, therefore, that the simultaneous finding of NDM and macroglossia should be a strong indicator for genetic testing. The genetic finding of paternal UPD6 allows prediction of a transient, rather than a permanent, form of diabetes mellitus and no increased recurrence risk of transient NDM in subsequent pregnancies. Marquis et al. (2000) described 2 patients who suffered from transient neonatal diabetes mellitus (TNDM) due to paternal isodisomy of chromosome 6. One patient, 5 years old at the time of report, had severe intrauterine growth retardation, but recovered normal growth parameters. The other patient, 12 years old at the time of report, had a normal birth weight but showed impaired postnatal growth; in addition to TNDM, this patient presented with cardiac and thyroid abnormalities. Mackay et al. (2006) reported 2 unrelated TNDM patients who had loss of maternal methylation both at 6q24 and at the centromeric DMR on 11p15.5 (KCNQ1OT1; 604115), which is involved in imprinting abnormalities in Beckwith-Wiedemann syndrome. Both patients presented with intrauterine growth retardation and TNDM without features of overgrowth. However, both had moderate macroglossia and abdominal wall defects, features occasionally found in both BWS and TNDM. In a review, Yorifuji et al. (2018) stated that the most important clinical feature of chromosome 6q24-related diabetes mellitus is a small-for-gestational-age birthweight, which reflects the lack of insulin in utero. They noted that many patients relapse after puberty. Diabetes is then permanent and is characterized by diminished insulin secretion without obesity and the absence of autoantibodies, which mimics maturity-onset diabetes of the young (MODY; see 125850). Diagnosis Bisulfite sequencing of the differentially methylated region (DMR) of 6q24 facilitated development of a diagnostic test for TNDM based on ratiometric methylation-specific PCR. Mackay et al. (2005) applied this method to 45 cases of TNDM, including 12 with paternal UPD6, 11 with an isolated methylation mutation at 6q24, 16 with a duplication of 6q24, and 6 of unknown etiology, together with 29 normal controls. All were correctly assigned. Mapping Mackay et al. (2008) studied a transient neonatal diabetes cohort which contained 13 probands with hypomethylation of multiple imprinted loci from 12 families. Six families were consanguineous, including 1 with 2 affected sibs. Genomewide SNP genotyping revealed a single region of homozygosity within 6p22.2-6p21.1 shared between 5 consanguineous pedigrees and the proband of the sixth, who was homozygous by descent. ### Mapping to Chromosome 6q Temple et al. (1996) reported a family with TNDM that showed linkage to D6S310, a marker in the 6q22-q23 region. Gardner et al. (1999) refined the critical region in transient NDM to a region of 6q24 defined by markers D6S1699 and D6S1010, within an interval of approximately 5.4 Mb. By further sequencing, Gardner et al. (2000) refined the region to a 300 to 400 kb region which contains several CpG islands. At one island, they noted differential DNA methylation between patients with paternal UPD of chromosome 6 and normal controls. In addition, 2 patients with TNDM, in whom neither paternal UPD of chromosome 6 nor duplication of 6q24 had been found, showed a DNA methylation pattern identical to that of patients with paternal UPD of chromosome 6. Control individuals showed a hemizygous methylation pattern. The authors concluded that TNDM can be associated with a methylation change and that there is a novel methylation imprint on chromosome 6 associated with TNDM. Pathogenesis ### Paternal Isodisomy or Duplication Temple et al. (1996) reported a family with a duplication in the 6q22-6q23 region associated with TNDM. The association between TNDM and either paternal isodisomy or duplication of 6q22-q23 raised the possibility of an imprinted gene in this location. Arthur et al. (1997) reported diabetes that developed in a baby girl immediately after birth and resolved after 7 weeks of insulin treatment. Because of her relatively coarse facial features and a protruding tongue, cytogenetic analysis was performed, showing an inverted duplication of 6q: invdup(6)(q22q23). The duplicated segment was located between DNA loci D6S308 and D6S1684. Arthur et al. (1997) concluded that the patient findings supported the assumption that an imprinted gene exists on 6q22-q23. The duplication in the patient reported by Arthur et al. (1997) was of paternal origin and spans the same region as that in a family reported by Temple et al. (1996). Gardner et al. (1998) analyzed samples from their cohort of patients with transient neonatal diabetes mellitus by uniparental disomy of chromosome 6 using polymorphic microsatellite repeat analysis. They reported the fifth case of paternal uniparental disomy of chromosome 6 associated with classic transient neonatal diabetes mellitus and estimated that uniparental disomy of chromosome 6 accounts for approximately one-fifth of cases of this syndrome. Since either duplication of a portion of chromosome 6q or uniparental disomy have been associated with transient neonatal diabetes mellitus, overexpression of an imprinted gene in this disorder is suggested. Prior to the report by Das et al. (2000), all patients with transient neonatal diabetes mellitus and uniparental disomy had had complete paternal isodisomy. Das et al. (2000) described a patient with neonatal diabetes, macroglossia, and craniofacial abnormalities who had partial paternal uniparental disomy of chromosome 6 involving the distal portion of 6q (6q24-qter). This observation demonstrated that mitotic recombination of chromosome 6 can also give rise to uniparental disomy and neonatal diabetes, a situation similar to that observed in Beckwith-Wiedemann syndrome (BWS; 130650), another imprinting disorder. Temple and Shield (2002) reviewed TNDM as a disorder of imprinting. They noted that 3 genetic mechanisms had been shown to result in TNDM: paternal uniparental isodisomy of chromosome 6, paternally inherited duplication of 6q24, and a methylation defect at a CpG island overlapping exon 1 of ZAC/HYMAI. ### Hypomethylation of Imprinted Loci Kant et al. (2005) reported female monochorionic, triamniotic, monozygous triplets, 2 of whom had TNDM. Methylation-specific PCR showed that the 2 affected children had isolated loss of maternal methylation within the TNDM DMR; the third unaffected child had normal PCR results. The discordant phenotype in 2 of 3 triplets suggested that the imprinting error may have preceded twinning in this case. Arima et al. (2001) showed that the differentially methylated CpG island that partially overlaps Zac1 (PLAGL1; 603044) and Hymai (606546) at the mouse locus syntenic for 6q24 is a likely imprinting control region (ICR) for the 120- to 200-kb domain. The region is unmethylated in sperm but probably methylated in oocytes, a difference that persists between parental alleles throughout pre- and postimplantation development. Within this ICR, there is a region that exhibits a high degree of homology between mouse and human and acts as a strong transcriptional repressor when methylated. In 5 of 6 TNDM patients studied with a normal karyotype, loss of methylation at 8 CpG sites within the region was demonstrated. ZAC/PLAGL1 is a transcriptional regulator of the type 1 receptor for pituitary adenylate cyclase-activating polypeptide (102981), potent known insulin secretagogue and an important mediator of autocrine control of insulin secretion in the pancreatic islet. The authors proposed that the ICR adjacent to ZAC may regulate expression of imprinted genes within the domain, and that epigenetic or genetic mutations of this region probably result in TNDM by affecting expression of ZAC in the pancreas and/or the pituitary. Mackay et al. (2006) performed DNA methylation analysis on a cohort of 12 patients with TNDM and total loss of maternal methylation on 6q24. Six of these patients showed a spectrum of methylation loss that was mosaic with respect to the extent of the methylation loss, the tissues affected, and the genetic loci involved. These patients had higher birth weight and were more phenotypically diverse than other TNDM patients, presumably reflecting the influence of dysregulation of multiple imprinted genes. Mackay et al. (2006) proposed the existence of a maternal hypomethylation syndrome and suggested that any patient with methylation loss at 1 maternally-methylated locus might also manifest methylation loss at other loci, potentially complicating or even confounding the clinical presentation. Molecular Genetics The mosaic DNA hypomethylation of multiple imprinted loci throughout the genome in over 50% of individuals with transient neonatal diabetes suggested disruption of imprinting not in the germline but during very early embryonic development. Using genomewide SNP genotyping, Mackay et al. (2008) identified a single region of homozygosity within chromosome 6p22.2-6p21.1 common to 5 consanguineous pedigrees and a proband who was homozygous by descent. On the basis of selection under the twin criteria of involvement in DNA binding or transcription regulation and expression in mouse oocyte or early zygote, and because of its expression in undifferentiated stem cell lineages and downregulation upon stem cell differentiation, Mackay et al. (2008) chose ZFP57 (612192) as the best candidate among the genes in the critical interval on 6p22.2-6p21.1. They identified ZFP57 mutations in 7 families with hypomethylation of multiple imprinted loci. Missense, nonsense, and frameshift mutations were identified. In addition to showing the cardinal epigenetic feature of TND, hypomethylation of the TND differentially methylated region (DMR), individuals with ZFP57 mutations were all hypomethylated at the PEG3 (601483) and GRB10 (601523) differentially methylated regions (DMRs). Hypomethylation of the KCNQ1OT1 (604115) and PEG1 (601029) DMRs was found in individuals with or without mutations in ZFP57. The diabetic presentation was typical for 6q TND in the 8 infant probands. Mackay et al. (2008) found that 6 of 9 individuals with TNDM and ZFP57 mutations had additional clinical features atypical of TNDM associated with hypomethylation at 6q24. Developmental delay was noted in 6 cases, including 2 with severe developmental delay and hypoplasia of the corpus callosum; however, ZFP57 mutation was also compatible with normal intelligence and development. Three probands were reported to have cardiac defects. These anomalies are less prevalent among individuals with hypomethylation of multiple imprinted loci but without mutations in ZFP57. Genotype/Phenotype Correlations In a study of 97 patients with diabetes diagnosed in the first 6 months of life whose diabetes remitted before the age of 5 years, 64 of whom had previously been reported, Flanagan et al. (2007) found that 70 of 97 (72%) had an abnormality at the 6q24 locus: 27 (39%) had paternal uniparental isodisomy, 28 (40%) had a duplication of the paternal allele, and 15 (22%) had a methylation defect. Of the remaining 28 TNDM patients without 6q24 abnormalities, 13 were found to have a mutation in the ABCC8 gene (600509) and 12 in the KCNJ11 gene (600937); in 3 patients no mutation was found. There were no significant differences in clinical characteristics between patients with ABCC8 and KCNJ11 mutations, whereas patients with a 6q24 abnormality had a significantly lower birth weight and an earlier diagnosis and remission than patients with K(ATP) channel mutations (p less than 0.001 for all). Atypical phenotypes were observed in all 3 patients in whom the genetic etiology was not defined, including premature birth, epilepsy, and multiple episodes of relapse and remission. Of 16 Japanese patients with TNDM, Suzuki et al. (2007) identified the 6q24 abnormality in 11 and a KCNJ11 mutation in 2; of 15 patients with PNDM, they identified a KCNJ11 mutation in 7 and an ABCC8 mutation in 2. Compared to patients with a KCNJ11 mutation, patients with the 6q24 abnormality had earlier onset of diabetes, a lower frequency of diabetic ketoacidosis at onset, and a higher proportion of patients with macroglossia at initial presentation. Diatloff-Zito et al. (2007) reported a group of 13 sporadic transient neonatal diabetes cases, including 5 with birth defects (congenital abnormalities of heart, brain, and bone) and 8 without. Two of the patients had paternal uniparental disomy-6 (UPD6); of the remaining 11 cases, 2 had complete and 3 had partial loss of the maternal methylation signature upstream of the ZAC1-HYMAI imprinted genes in non-UPD cases. There was 1 case of hemizygous deletion among all 13 cases, in a patient with severe congenital malformations. Diatloff-Zito et al. (2007) raised the hypothesis that the deletion had an effect on regulatory elements critical for imprinting and tissue-specific gene expression in early development. Animal Model The inheritance pattern of transient neonatal diabetes mellitus implicates overexpression of 1 or both genes within the TNDM locus: ZAC (603044), which encodes a proapoptotic zinc finger protein, and HYMAI (606546), which encodes an untranslated mRNA. To investigate the consequences for pancreatic function, Ma et al. (2004) developed a high-copy transgenic mouse line carrying the human TNDM locus. Neonates of this line displayed hyperglycemia, and older adults, glucose intolerance. Neonatal hyperglycemia occurred only on paternal transmission, analogous to paternal dependence of TNDM in humans. The embryonic pancreata of these mice showed reductions in expression of endocrine differentiation factors and numbers of insulin-staining structures. By contrast, beta-cell mass was normal or elevated at all postnatal stages, whereas pancreatic insulin content in neonates and peak serum insulin levels after glucose infusion in adults were reduced. Expression of human ZAC and HYMAI in these transgenic mice thus recapitulated key features of TNDM and implicated impaired development of the endocrine pancreas and beta-cell function in disease pathogenesis. Other Features Hurst and McVean (1997) examined the conflict theory for the evolution of genomic imprinting. The theory proposes that imprinting is an intraindividual manifestation of classic parent-offspring conflict. The theory predicts that imprinted genes expressed from the paternally derived genome should be enhancers of pre- and postnatal growth, while those expressed from the maternally derived genome should be growth suppressors. Hurst and McVean (1997) examined this prediction by reviewing the literature on growth of human and mouse progeny that inherited both copies (or part thereof) of a particular chromosome from only 1 parent. They found that much of the data do not support the conflict theory hypothesis. They pointed to paternal uniparental disomy of chromosome 6 (UPD6), which is associated with severe growth retardation. The conflict theory would suggest that growth should be enhanced. In their Figure 1, they illustrated the patient reported by Ferguson and Milner (1970). INHERITANCE \- Autosomal dominant (loss of maternal allele) GROWTH Other \- Intrauterine growth retardation \- Severe failure to thrive METABOLIC FEATURES \- Dehydration ENDOCRINE FEATURES \- Transient neonatal diabetes mellitus (TNDM) \- Late predisposition to type 2 (insulin resistant) diabetes LABORATORY ABNORMALITIES \- Hyperglycemia MISCELLANEOUS \- Imprinted disorder \- Usual resolution within 6 months \- Insulin therapy usually required MOLECULAR BASIS \- Caused by loss of maternal allele at 6q24 \- Caused by mutation in the homolog of the mouse zinc finger protein 57 gene (ZFP57, 612192.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy

DIABETES MELLITUS, TRANSIENT NEONATAL, 1

c1832386

omim

https://www.omim.org/entry/601410

{"doid": ["0060334"], "mesh": ["C563322"], "omim": ["601410"], "orphanet": ["99886"], "synonyms": ["Alternative titles", "6q24-RELATED DIABETES MELLITUS", "TNDM", "DMTN"], "genereviews": ["NBK1534"]}

A number sign (#) is used with this entry because individuals heterozygous for mutation in the ABCC6 gene (603234) in the overwhelming majority of cases express limited manifestations of the pseudoxanthoma elasticum phenotype. In rare cases heterozygosity for mutations in the ABCC6 gene appears to result in expression of the full PXE phenotype in 2 generations (see 603234.0018). A digenic form of PXE resulting from an ABCC6 mutation (603234.0001) and a GGCX mutation (137167.0012) has been reported. For a phenotypic description of PXE, see 264800. Clinical Features Hausser and Anton-Lamprecht (1991) described a family in which the mother and grandmother died because of major vascular complications of PXE. Three adolescent sibs showed no clinical manifestations of PXE. However, ultrastructural investigation of overtly normal skin in sites of predilection gave a positive diagnosis. Dermal connective tissue showed a specific aberrant pattern; elastin (130160) of elastic fibers regularly contained small foci of calcification resembling those in perilesional skin of the mother and other PXE patients; in collagen bundles adjacent to altered elastic fibers, collagen fibrils occurred with thickened diameters and flower-like contours. Van Soest et al. (1997) reported a family from a genetically isolated population in the Netherlands with autosomal recessive PXE in which vascular symptoms appeared in 40 to 50% of the heterozygotes. Molecular Genetics Bacchelli et al. (1999) and Sherer et al. (2001) presented evidence that heterozygous mutant family members of affected individuals present limited manifestations of PXE. Bergen et al. (2000), Le Saux et al. (2000), and Ringpfeil et al. (2000) identified missense, nonsense, and splice site mutations, as well as deletions and insertions, in the ABCC6 gene (603234) accounting for pseudoxanthoma elasticum (264800). Mutations appeared to represent autosomal recessive (Le Saux et al., 2000) and autosomal dominant (Bergen et al., 2000) modes of inheritance, and sporadic cases. The R114X mutation (603234.0001) was found in families segregating autosomal dominant PXE and in families segregating autosomal recessive PXE. Plomp et al. (2004) described a family in which criteria for 'definite' PXE were met in 2 generations and in which an arg1459-to-cys substitution (R1459C) in the ABCC protein was detected on 1 allele only (603234.0018). They stated that the R1459C mutation might be one that could cause PXE in the heterozygous state. In their review of families with putative autosomal dominant PXE, including this family and 2 others examined by them, the authors noted that they did not find a single family with definite PXE in 3 or more generations. Bergen (2006) stated that the family with the apparently heterozygous R1459C mutation studied by Plomp et al. (2004) remained 'an interesting puzzle and is perhaps the always existing 'exception to the rule'.' Miksch et al. (2005) performed a mutation screen in ABCC6 using haplotype analysis in conjunction with direct sequencing to achieve a mutation detection rate of 97%. The resultant data indicated that the inheritance of PXE is exclusively autosomal recessive, and that all mutations in the ABCC6 gene associated with PXE appear to lead to loss of function of the protein. The authors suggested that clinical carriers of the trait with a haplotypic heterozygous allelic status for one of the familial disease alleles may express a forme fruste of the disorder that can be characterized, in part, by category II diagnostic criteria (Neldner and Struk, 2002) according to the consensus conference (Lebwohl et al., 1994). Such carriers may have positive skin biopsy of nonlesional skin and/or show mottled hyperpigmentation or angioid streaks, but will not exhibit the long-term manifestations and complications of the disorder that are the consequences of the loss of function of both ABCC6 alleles. Miksch et al. (2005) stated that in the families examined by them, none of the heterozygotes for a large deletion showed any apparent clinical signs of PXE according to category I diagnostic criteria. ### PXE, Forme Fruste, Digenic, ABCC6/GGCX In a woman and her sister with biopsy-confirmed PXE, Li et al. (2009) identified compound heterozygosity for a mutation in the ABCC6 gene (R1141X; 603234.0001) mutation and a mutation in the GGCX gene (V255M; 137167.0012). Neither had evidence of a coagulopathy, but skin biopsies showed undercarboxylated matrix gla proteins (MGP; 154870) in the areas of abnormal mineralization. Since R1141X in the heterozygous state is usually not associated with clinical features, the findings suggested that women had digenic inheritance of PXE. In contrast, 2 other family members who were compound heterozygous for R1141X and another mutation in the GGCX gene (S300F; 137167.0013) had no signs of either disorder on clinical exam but refused to participate in further clinical testing. Plasma levels of total undercarboxylated MGP in the 2 clinically unaffected individuals were at the lower end of normal. Although the reasons for the lack of clinical findings in these latter individuals remained unclear, Li et al. (2009) concluded that undercarboxylation of MGP plays a critical role in aberrant mineralization of tissues in PXE. History Wise (1966) stated that about a quarter of all families with 2 or more cases of PXE have cases in successive generations. He noted that no quantitative or qualitative difference between the cases could be discerned in families with successive generations affected (autosomal dominant) and families with unaffected but consanguineous parents (autosomal recessive). In a series of 100 personally studied cases, Neldner (1988) found no instance of 3-generation involvement. Indeed, only 3 patients of the 100 were considered to have autosomal dominant inheritance: a mother-daughter pair and a third patient whose father had biopsy-proven PXE but was not a member of the study. In addition, there were 3 families with 3 affected sibs each and 4 families with 2 affected sibs. The 100 patients came from 88 separate kindreds. Three of the patients from single-patient sibships had cousins with PXE. Struk et al. (1997) stated that an autosomal dominant pattern of transmission of PXE occurs in approximately 10% of affected families. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Angioid streaks of the retina \- Macular degeneration \- Decreased visual acuity \- Myopia \- Blue sclerae \- Retinal hemorrhage \- Peau d'orange retinal changes \- Salmon spots Mouth \- High arched palate \- Yellowish lip mucosal nodules CARDIOVASCULAR Heart \- Mitral valve prolapse Vascular \- Angina \- Claudication \- Premature occlusive vascular disease \- Arteriosclerosis \- Medial calcification of medium-sized and major arteries \- Diminished or absent peripheral pulses CHEST Ribs Sternum Clavicles & Scapulae \- Pectus deformities ABDOMEN Gastrointestinal \- Gastrointestinal hemorrhage SKELETAL Skull \- Calcification of falx cerebri Spine \- Kyphosis \- Scoliosis SKIN, NAILS, & HAIR Skin \- Small, yellow papules (mouth, neck, axilla, elbows, groin, periumbilical region) \- Peau d'orange \- Elastosis perforans serpiginosa NEUROLOGIC Central Nervous System \- Cerebral hemorrhage MISCELLANEOUS \- Allelic to autosomal recessive PXE ( 264800 ) MOLECULAR BASIS \- Caused by mutations in the ATP-binding cassette, subfamily C, member 6 gene (ABCC6, 603234.0005 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy

PSEUDOXANTHOMA ELASTICUM, FORME FRUSTE

c0033847

omim

https://www.omim.org/entry/177850

{"doid": ["2738"], "mesh": ["D011561"], "omim": ["177850"], "orphanet": ["758"], "genereviews": ["NBK1113"]}

Paroxysmal extreme pain disorder is a condition characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. The area of flushing typically corresponds to the site of the pain. The pain attacks experienced by people with paroxysmal extreme pain disorder usually last seconds to minutes, but in some cases can last hours. These attacks can start as early as infancy. Early in life, the pain is typically concentrated in the lower part of the body, especially around the rectum, and is usually triggered by a bowel movement. Some children may develop constipation, which is thought to be due to fear of triggering a pain attack. Pain attacks in these young children may also be accompanied by seizures, slow heartbeat, or short pauses in breathing (apnea). As a person with paroxysmal extreme pain disorder ages, the location of pain changes. Pain attacks switch from affecting the lower body to affecting the head and face, especially the eyes and jaw. Triggers of these pain attacks include changes in temperature (such as a cold wind) and emotional distress as well as eating spicy foods and drinking cold drinks. Paroxysmal extreme pain disorder is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. ## Frequency Paroxysmal extreme pain disorder is a rare condition; approximately 80 affected individuals have been described in the scientific literature. ## Causes Mutations in the SCN9A gene cause paroxysmal extreme pain disorder. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. The SCN9A gene mutations that cause paroxysmal extreme pain disorder result in NaV1.7 sodium channels that do not close completely when it is turned off, allowing sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the pain attacks experienced by people with paroxysmal extreme pain disorder. It is unknown why the pain attacks associated with this condition change location over time or what causes the other features of this condition such as seizures and changes in breathing. ### Learn more about the gene associated with Paroxysmal extreme pain disorder * SCN9A ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy

Paroxysmal extreme pain disorder

c1833661

medlineplus

https://medlineplus.gov/genetics/condition/paroxysmal-extreme-pain-disorder/

{"gard": ["12854"], "mesh": ["C563475"], "omim": ["167400"], "synonyms": []}

## Clinical Features Temtamy and McKusick (1978) observed a mother and son with double nails on the little toes--one on top of the other. The woman's grandson through an unaffected daughter had postaxial polydactyly. Limbs \- Double nails on fifth toes Inheritance \- Autosomal dominant ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy

DOUBLE NAIL FOR FIFTH TOE

c1852023

omim

https://www.omim.org/entry/126500

{"mesh": ["C565090"], "omim": ["126500"]}

Opioid use disorder Other namesOpioid addiction,[1] problematic opioid use,[1] opioid abuse,[2] opioid dependence[3] Molecular structure of morphine SpecialtyAddiction Medicine, Psychiatry SymptomsStrong desire to use opioids, increased tolerance to opioids, failure to meet obligations, trouble with reducing use, withdrawal syndrome with discontinuation[4][5] ComplicationsOpioid overdose, hepatitis C, marriage problems, unemployment, poverty[4][5] DurationLong term[6] CausesOpioids[3] Diagnostic methodBased on criteria in the DSM-5[4] Differential diagnosisAlcoholism TreatmentOpioid replacement therapy, behavioral therapy, twelve-step programs, take home naloxone[7][8][9] MedicationBuprenorphine, methadone, naltrexone[7][10] Frequency27 million (c. 0.4%)[11][4] Deaths122,000 (2015)[12] Opioid use disorder (OUD) is a substance use disorder relating to the use of an opioid. Any such disorder causes significant impairment or distress.[3] Signs of the disorder include a strong desire to use opioids, increased tolerance to opioids, difficulty fulfilling obligations, trouble reducing use, and withdrawal symptoms with discontinuation.[4][5] Opioid withdrawal symptoms may include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood.[5] Addiction and dependence are components of a substance use disorder.[13] Complications may include opioid overdose, suicide, HIV/AIDS, hepatitis C, and problems at school, work, or home.[4][5] Opioids include substances such as heroin, morphine, fentanyl, codeine,dihydrocodeine, oxycodone, and hydrocodone.[5][6] In the United States, a majority of heroin users begin by using prescription opioids, that may also be bought illegally.[14][15] Risk factors for misuse include a history of substance use, substance use among family and friends, mental illness, low socioeconomic status, and race.[16][17] Diagnosis may be based on criteria by the American Psychiatric Association in the DSM-5.[4] If more than two of eleven criteria are present during a year, the diagnosis is said to be present.[4] If a person is appropriately taking opioids for a medical condition, issues of tolerance and withdrawal do not apply.[4] Individuals with an opioid use disorder are often treated with opioid replacement therapy using methadone or buprenorphine.[7] Being on such treatment reduces the risk of death.[7] Additionally, individuals may benefit from cognitive behavioral therapy, other forms of support from mental health professionals such as individual or group therapy, twelve-step programs, and other peer support programs.[8] The medication naltrexone may also be useful to prevent relapse.[10] Naloxone is useful for treating an opioid overdose and giving those at risk naloxone to take home is beneficial.[9] In 2013, opioid use disorders affected about 0.4% of people.[4] As of 2016, about 27 million people are affected.[11] Long term opioid use occurs in about 4% of people following their use for trauma or surgery related pain.[18] Onset is often in young adulthood.[4] Males are affected more often than females.[4] It resulted in 122,000 deaths worldwide in 2015,[12] up from 18,000 deaths in 1990.[19] In the United States during 2016, there were more than 42,000 deaths due to opioid overdose, of which more than 15,000 were the result of heroin use.[20] ## Contents * 1 Signs and symptoms * 1.1 Withdrawal * 1.2 Opioid intoxication * 1.3 Opioid overdose * 2 Cause * 3 Mechanism * 3.1 Addiction * 3.2 Dependence * 3.3 Opioid receptors * 3.3.1 118A>G variant * 3.3.2 Non-opioid receptor genes * 4 Diagnosis * 5 Prevention * 5.1 Opioid related deaths * 6 Management * 6.1 Medications * 6.1.1 Methadone * 6.1.2 Buprenorphine * 6.1.3 Other opioids * 6.1.4 Naltrexone * 6.2 Behavioral therapy * 6.2.1 Cognitive behavioral therapy * 6.2.2 Twelve-step programs * 6.2.3 Digital care programs * 7 Epidemiology * 7.1 United States * 8 History * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] Material used for intravenous injection of opioids Signs and symptoms include:[4][5] * Drug seeking behavior * Increased use over time * Legal or social ramifications secondary to drug use * Multiple prescriptions from different providers * Multiple medical complications from drug use (HIV/AIDS, hospitalizations, abscesses) * Opioid cravings * Withdrawal symptoms Addiction and dependence are components of a substance use disorder and addiction represents the more severe form.[13] Opioid dependence can occur as physical dependence, psychological dependence, or both.[21] ### Withdrawal[edit] Opioid withdrawal can occur with a sudden decrease in, or the cessation of opioids after prolonged use.[22][23] Onset of withdrawal depends on which opioid was used last.[24] With heroin this typically occurs five hours after use, while with methadone it might not occur until two days later.[24] The length of time that major symptoms occur also depends on the opioid used.[24] For heroin withdrawal, symptoms are typically greatest at two to four days, and can last for up to two weeks.[25][24] Less significant symptoms may remain for an even longer period, in which case the withdrawal is known as post-acute-withdrawal syndrome.[24] * Agitation[4] * Anxiety[4] * Muscle pains[4] * Increased tearing[4] * Trouble sleeping[4] * Runny nose[4] * Sweating[4] * Yawning[4] * Goose bumps[4] * Dilated pupils[4] * Diarrhea[4] * Fast heart rate[24] * High blood pressure[24] * Abdominal cramps[24] * Shakiness[24] * Cravings[24] * Sneezing[24] Treatment of withdrawal may include methadone and buprenorphine. Medications for nausea or diarrhea may also be used.[23] ### Opioid intoxication[edit] Signs and symptoms of opioid intoxication include:[5][26] * Decreased perception of pain * Euphoria * Confusion * Desire to sleep * Nausea * Constipation * Miosis * Bradycardia * Hypotension * Hypokinesis (slowed movement) * Head nodding * Slurred speech * Hypothermia ### Opioid overdose[edit] Main article: Opioid overdose Fentanyl 2 mg. A lethal dose in most people.[27] Signs and symptoms of opioid overdose include, but are not limited to:[28] * Pin-point pupils may occur. Patient presenting with dilated pupils may still be suffering an opioid overdose. * Decreased heart rate * Decreased body temperature * Decreased breathing * Altered level of consciousness. People may be unresponsive or unconscious. * Pulmonary edema (fluid accumulation in the lungs) * Shock * Death ## Cause[edit] Opioid use disorder can develop as a result of self-medication, though this is controversial.[29] Scoring systems have been derived to assess the likelihood of opiate addiction in chronic pain patients.[30] Prescription opioids are the source of nearly half of misused opioids and the majority of these are initiated for trauma or surgery pain management.[18] According to position papers on the treatment of opioid dependence published by the United Nations Office on Drugs and Crime and the World Health Organization, care providers should not treat opioid use disorder as the result of a weak moral character or will but as a medical condition.[16][31][32] Some evidence suggests the possibility that opioid use disorders occur due to genetic or other chemical mechanisms which may be difficult to identify or change, such as dysregulation of brain circuitry involving reward and volition. However, the exact mechanisms involved are unclear, leading to debate regarding where the influence of biology and free will.[33][34] ## Mechanism[edit] ### Addiction[edit] Addiction is a brain disorder characterized by compulsive drug use despite adverse consequences.[13][35][36][37] Addiction is a component of a substance use disorder and represents the most severe form of the disorder.[13] Overexpression of the gene transcription factor ΔFosB in the nucleus accumbens plays a crucial role in the development of an addiction to opioids and other addictive drugs by sensitizing drug reward and amplifying compulsive drug-seeking behavior.[35][38][39][40] Like other addictive drugs, overuse of opioids leads to increased ΔFosB expression in the nucleus accumbens.[38][39][40][41] Opioids affect dopamine neurotransmission in the nucleus accumbens via the disinhibition of dopaminergic pathways as a result of inhibiting the GABA-based projections to the ventral tegmental area (VTA) from the rostromedial tegmental nucleus (RMTg), which negatively modulate dopamine neurotransmission.[42][43] In other words, opioids inhibit the projections from the RMTg to the VTA, which in turn disinhibits the dopaminergic pathways that project from the VTA to the nucleus accumbens and elsewhere in the brain.[42][43] Neuroimaging has shown functional and structural alterations in the brain.[44] A 2017 study showed that chronic intake of opioids, such as heroin, may cause long-term effects in the orbitofrontal area (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety.[45] Moreover, neuroimaging and neuropsychological studies demonstrated dysregulation of circuits associated with emotion, stress and high impulsivity.[46] ### Dependence[edit] Drug dependence is an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake).[35][36][37] Dependence is a component of a substance use disorder.[13][47] Opioid dependence can manifest as physical dependence, psychological dependence, or both.[21][36][47] Increased brain-derived neurotrophic factor (BDNF) signaling in the ventral tegmental area (VTA) has been shown to mediate opioid-induced withdrawal symptoms via downregulation of insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and mechanistic target of rapamycin complex 2 (mTORC2).[35][48] As a result of downregulated signaling through these proteins, opiates cause VTA neuronal hyperexcitability and shrinkage (specifically, the size of the neuronal soma is reduced).[35] It has been shown that when an opiate-naive person begins using opiates in concentrations that induce euphoria, BDNF signaling increases in the VTA.[49] Upregulation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway by cAMP response element binding protein (CREB), a gene transcription factor, in the nucleus accumbens is a common mechanism of psychological dependence among several classes of drugs of abuse.[21][35] Upregulation of the same pathway in the locus coeruleus is also a mechanism responsible for certain aspects of opioid-induced physical dependence.[21][35] ### Opioid receptors[edit] A genetic basis for the efficacy of opioids in the treatment of pain has been demonstrated for several specific variations; however, the evidence for clinical differences in opioid effects is ambiguous. The pharmacogenomics of the opioid receptors and their endogenous ligands have been the subject of intensive activity in association studies. These studies test broadly for a number of phenotypes, including opioid dependence, cocaine dependence, alcohol dependence, methamphetamine dependence/psychosis, response to naltrexone treatment, personality traits, and others. Major and minor variants have been reported for every receptor and ligand coding gene in both coding sequences, as well as regulatory regions. Newer approaches shift away from analysis of specific genes and regions, and are based on an unbiased screen of genes across the entire genome, which have no apparent relationship to the phenotype in question. These GWAS studies yield a number of implicated genes, although many of them code for seemingly unrelated proteins in processes such as cell adhesion, transcriptional regulation, cell structure determination, and RNA, DNA, and protein handling/modifying.[50] #### 118A>G variant[edit] While over 100 variants have been identified for the opioid mu-receptor, the most studied mu-receptor variant is the non-synonymous 118A>G variant, which results in functional changes to the receptor, including lower binding site availability, reduced mRNA levels, altered signal transduction, and increased affinity for beta-endorphin. In theory, all of these functional changes would reduce the impact of exogenous opioids, requiring a higher dose to achieve the same therapeutic effect. This points to a potential for greater addictive capacity in these individuals who require higher dosages to achieve pain control. However, evidence linking the 118A>G variant to opioid dependence is mixed, with associations shown in a number of study groups, but negative results in other groups. One explanation for the mixed results is the possibility of other variants which are in linkage disequilibrium with the 118A>G variant and thus contribute to different haplotype patterns that more specifically associated with opioid dependence.[51] #### Non-opioid receptor genes[edit] The preproenkephalin gene, PENK, encodes for the endogenous opiates that modulate pain perception, and are implicated in reward and addiction. (CA) repeats in the 3' flanking sequence of the PENK gene was associated with greater likelihood of opiate dependence in repeated studies. Variability in the MCR2 gene, encoding melanocortin receptor type 2 has been associated with both protective effects and increased susceptibility to heroin addiction. The CYP2B6 gene of the cytochrome P450 family also mediates breakdown of opioids and thus may play a role in dependence and overdose.[52] ## Diagnosis[edit] The DSM-5 guidelines for the diagnosis of opioid use disorder require that the individual has a significant impairment or distress related to opioid uses.[4] To make the diagnosis two or more of eleven criteria must be present in a given year:[4] 1. More opioids are taken than intended 2. The individual is unable to decrease the number of opioids used 3. Large amounts of time are spent trying to obtain opioids, use opioids, or recover from taking them 4. The individual has cravings for opioids 5. Difficulty fulfilling professional duties at work or school 6. Continued use of opioids leading to social and interpersonal consequences 7. Decreased social or recreational activities 8. Using opioids despite being in physically dangerous settings 9. Continued use despite opioids worsening physical or psychological health (i.e. depression, constipation) 10. Tolerance 11. Withdrawal The severity can be classified as mild, moderate, or severe based on the number of criteria present.[6] ## Prevention[edit] The CDC gives specific recommendations for prescribers regarding initiation of opioids, clinically appropriate use of opioids, and assessing possible risks associated with opioid therapy.[53] Large retail pharmacy chains in the US are implementing protocols, guidelines, and initiatives to take back unused opioids, providing naloxone kits, and being vigilant for suspicious prescriptions.[54][55] Insurance programs can help limit opioid use by setting quantity limits on prescriptions or requiring prior authorizations for certain medications.[56] ### Opioid related deaths[edit] Naloxone is used for the emergency treatment of an overdose.[57] It can be given by many routes (e.g., intramuscular, intravenous, subcutaneous, intranasal, and inhalation) and acts quickly by displacing opioids from opioid receptors and preventing activation of these receptors by opioids.[58] Naloxone kits are recommended for laypersons who may witness an opioid overdose, for individuals with large prescriptions for opioids, those in substance use treatment programs, or who have been recently released from incarceration.[59] Since this is a life-saving medication, many areas of the United States have implemented standing orders for law enforcement to carry and give naloxone as needed.[60][61] In addition, naloxone could be used to challenge a person's opioid abstinence status prior to starting a medication such as naltrexone, which is used in the management of opioid addiction.[62] Good Samaritan laws typically protect bystanders that administer naloxone. In the United States, at least 40 states have Good Samaritan laws to encourage bystanders to take action without fear of prosecution.[63] As of 2019, 48 states allow for a pharmacist to have the authority to distribute naloxone without an individual prescription.[64] ## Management[edit] Opioid use disorders typically require long-term treatment and care with the goal of reducing risks for the individual, reducing criminal behaviour, and improving the long-term physical and psychological condition of the person.[32] Some strategies aim to reduce drug use and lead to abstinence from opioids, while others attempt to stabilize on prescribed methadone or buprenorphine with continued replacement therapy indefinitely.[32] No single treatment works for everyone, so several strategies have been developed including therapy and drugs.[32][65]' As of 2013 in the US, there was a significant increase of prescription opioid abuse compared to illegal opiates like heroin.[66] This development has also implications for the prevention, treatment and therapy of opioid dependence.[67] Though treatment reduces mortality rates, the period during the first four weeks after treatment begins and the four weeks after treatment ceases are the times that carry the highest risk for drug-related deaths. These periods of increased vulnerability are significant because many of those in treatment leave programs during these critical periods.[7] ### Medications[edit] See also: Heroin-assisted treatment Opioid replacement therapy (ORT) involves replacing an opioid, such as heroin, with a longer acting but less euphoric opioid.[68][69] Commonly used drugs for ORT are methadone or buprenorphine which are taken under medical supervision.[69] As of 2018[update], buprenorphine/naloxone is preferentially recommended, as the addition of the opioid antagonist naloxone is believed to reduce the risk of abuse via injection or insufflation without causing impairment.[70][71] The driving principle behind ORT is the program's capacity to facilitate a resumption of stability in the user's life, while the patient experiences reduced symptoms of drug withdrawal and less intense drug cravings; a strong euphoric effect is not experienced as a result of the treatment drug.[69] In some countries (not the US, or Australia),[69] regulations enforce a limited time for people on ORT programs that conclude when a stable economic and psychosocial situation is achieved. (People with HIV/AIDS or hepatitis C are usually excluded from this requirement.) In practice, 40–65% of patients maintain abstinence from additional opioids while receiving opioid replacement therapy and 70–95% can reduce their use significantly.[69] Along with this is a concurrent elimination or reduction in medical (improper diluents, non-sterile injecting equipment), psychosocial (mental health, relationships), and legal (arrest and imprisonment) issues that can arise from the use of illegal opioids.[69] Clonidine or lofexidine can help treat the symptoms of withdrawal.[72] Participation in methadone and buprenorphine treatment reduces the risk of mortality due to overdose.[7] The starting of methadone and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies.[7] ORT has proven to be the most effective treatment for improving the health and living condition of people experiencing illegal opiate use or dependence, including mortality reduction[69][73][7] and overall societal costs, such as the economic loss from drug-related crime and healthcare expenditure.[69] ORT is endorsed by the World Health Organization, United Nations Office on Drugs and Crime and UNAIDS as being effective at reducing injection, lowering risk for HIV/AIDS, and promoting adherence to antiretroviral therapy.[7] Buprenorphine and methadone work by reducing opioid cravings, easing withdrawal symptoms, and blocking the euphoric effects of opioids via cross-tolerance,[74] and in the case of buprenorphine, a high-affinity partial agonist, also due to opioid receptor saturation.[75] It is this property of buprenorphine that can induce acute withdrawal when administered before other opioids have left the body. Naltrexone, a μ-opioid receptor antagonist, also blocks the euphoric effects of opioids by occupying the opioid receptor, but it does not activate it, so it does not produce sedation, analgesia, or euphoria, and thus it has no potential for abuse or diversion.[76][77] In the United States, since March 2020 as a result of the COVID-19 pandemic, buprenorphine may be dispensed via telemedicine.[78] #### Methadone[edit] * v * t * e Receptor binding affinities of isomers of methadone[79][80] Compound Affinities (Ki, in nM) Ratios MOR DOR KOR SERT NET NMDAR M:D:K SERT:NET Racemic methadone 1.7 435 405 ND ND 2,500–8,300 1:256:238 ND Dextromethadone 19.7 960 1,370 992 12,700 2,600–7,400 1:49:70 1:13 Levomethadone 0.945 371 1,860 14.1 702 2,800–3,400 1:393:1968 1:50 Main article: Methadone maintenance Methadone maintenance treatment (MMT), a form of opioid replacement therapy, reduces and/or eliminates the use of illegal opiates, the criminality associated with opiate use, and allows patients to improve their health and social productivity.[81][82] Methadone is a μ-opioid receptor agonist. If initial doses during the beginning of treatment are too high or are concurrent with illicit opioid use, this may present an increased risk of death from overdose.[7] In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with opiate injection, such as hepatitis and HIV.[81] The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with opiates. Methadone maintenance is medically safe and non-sedating.[81] It is also indicated for pregnant women addicted to opiates.[81] For individuals who wish to completely move away from drugs, they can start a methadone reduction program. A methadone reduction program is where an individual is prescribed an amount of methadone which is increased until withdrawal symptoms subside, after a period of stability, the dose will then be gradually reduced until the individual is either free of the need for methadone or is at a level which allows a switch to a different opiate with an easier withdrawal profile, such as suboxone. Methadone toxicity has been shown to be associated with specific phenotypes of CYP2B6.[83] Some impairment in cognition has been demonstrated in those using methadone.[46][84] Currently, 55 countries worldwide use methadone replacement therapy, while some countries such as Russia do not.[85] #### Buprenorphine[edit] Buprenorphine/naloxone tablet Buprenorphine is a partial opioid receptor agonist. Unlike methadone and other full opioid receptor agonists, buprenorphine is less likely to cause respiratory depression due to its ceiling effect.[76] Treatment with buprenorphine may be associated with reduced mortality.[7] Buprenorphine under the tongue is often used to manage opioid dependence. Preparations were approved for this use in the United States in 2002.[86] Some formulations of buprenorphine incorporate the opiate antagonist naloxone during the production of the pill form to prevent people from crushing the tablets and injecting them, instead of using the sublingual (under the tongue) route of administration.[69] #### Other opioids[edit] See also: Heroin maintenance Evidence of effects of heroin maintenance compared to methadone are unclear as of 2010.[87] A Cochrane review found some evidence in opioid users who had not improved with other treatments.[88] In Switzerland, Germany, the Netherlands, and the United Kingdom, long-term injecting drug users who do not benefit from methadone and other medication options may be treated with injectable heroin that is administered under the supervision of medical staff.[89] Other countries where it is available include Spain, Denmark, Belgium, Canada, and Luxembourg.[90] Dihydrocodeine in both extended-release and immediate-release form are also sometimes used for maintenance treatment as an alternative to methadone or buprenorphine in some European countries.[91] Dihydrocodeine is an opioid agonist.[92] It may be used as a second line treatment.[93] A 2020 systematic review found low quality evidence that dihydrocodeine may be no more effective than other routinely used medication interventions in reducing illicit opiate use.[94] An extended-release morphine confers a possible reduction of opioid use and with fewer depressive symptoms but overall more adverse effects when compared to other forms of long-acting opioids. Retention in treatment was not found to be significantly different.[95] It is used in Switzerland and more recently in Canada.[96] #### Naltrexone[edit] Naltrexone is an opioid receptor antagonist used for the treatment of opioid addiction.[97][98] Naltrexone is not as widely used as buprenorphine or methadone for OUD due to low rates of patient acceptance, non-adherence due to daily dosing, and difficulty achieving abstinence from opioids before beginning treatment. Additionally, dosing naltrexone after recent opioid use could lead to precipitated withdrawal. Conversely, naltrexone antagonism at the opioid receptor can be overcome with higher doses of opioids.[99] Naltrexone monthly IM injections received FDA approval in 2010, for the treatment of opioid dependence in abstinent opioid users.[97][100] ### Behavioral therapy[edit] Further information: Addiction § Behavioral therapy #### Cognitive behavioral therapy[edit] Cognitive behavioral therapy (CBT), a form of psychosocial intervention that is used to improve mental health, may not be as effective as other forms of treatment.[101] CBT primarily focuses on an individual's coping strategies to help change their cognition, behaviors and emotions about the problem. This intervention has demonstrated success in many psychiatric conditions (e.g., depression) and substance use disorders (e.g., tobacco).[102] However, the use of CBT alone in opioid dependence has declined due to the lack of efficacy, and many are relying on medication therapy or medication therapy with CBT, since both were found to be more efficacious than CBT alone. A form of CBT therapy known as motivational interviewing (MI) is often used opioid use disorder. MI leverages a person intrinsic motivation to recover through education, formulation of relapse prevention strategies, reward for adherence to treatment guidelines, and positive thinking to keep motivation high—which are based on a person's socioeconomic status, gender, race, ethnicity, sexual orientation, and their readiness to recover.[103][104][105] #### Twelve-step programs[edit] Main article: Twelve-step program While medical treatment may help with the initial symptoms of opioid withdrawal, once the first stages of withdrawal are through, a method for long-term preventative care is attendance at 12-step groups such as Narcotics Anonymous.[106] Narcotics Anonymous is a global service that provides multilingual recovery information and public meetings free of charge.[107] Some evidence supports the use of these programs in adolescents as well.[108] The 12-step program is an adapted form of the Alcoholics Anonymous program. The program strives to help create behavioural change by fostering peer-support and self-help programs. The model helps assert the gravity of addiction by enforcing the idea that addicts must surrender to the fact that they are addicted and be able to recognize the problem. It also helps maintain self-control and restraint to help promote one's capabilities.[109] #### Digital care programs[edit] Digital care programs (see telehealth or digital health) have increased in number since the Coronavirus pandemic mandated the increased usage of remote healthcare options. These programs offer treatment and continuing care remotely, via smartphone and desktop applications. This often includes remote substance testing, access to peer support meetings, recovery coaching or therapy, and self-guided learning modules. Examples of digital care programs for opioid use disorder include: Chess, Pear Therapeutics, DynamiCare Health, Kaden Health and WeConnect. ## Epidemiology[edit] See also: Opioid epidemic Globally, the number of people with opioid dependence increased from 10.4 million in 1990 to 15.5 million in 2010.[7] In 2016, the numbers rose to 27 million people who experienced this disorder.[11] Opioid use disorders resulted in 122,000 deaths worldwide in 2015,[12] up from 18,000 deaths in 1990.[19] Deaths from all causes rose from 47.5 million in 1990 to 55.8 million in 2013.[19][12] ### United States[edit] Main article: Opioid epidemic in the United States Overdose deaths involving opioids, United States. Deaths per 100,000 population by year.[110] The current epidemic of opioid abuse is the most lethal drug epidemic in American history.[15] In 2008, there were four times as many deaths due to overdose than there were in 1999.[111] In 2017, in the US, "the age-adjusted drug poisoning death rate involving opioid analgesics increased from 1.4 to 5.4 deaths per 100,000 population between 1999 and 2010, decreased to 5.1 in 2012 and 2013, then increased to 5.9 in 2014, and to 7.0 in 2015. The age-adjusted drug poisoning death rate involving heroin doubled from 0.7 to 1.4 deaths per 100,000 resident population between 1999 and 2011 and then continued to increase to 4.1 in 2015."[112] In 2017, the U.S. Department of Health and Human Services (HHS) announced a public health emergency due to an increase in the misuse of opioids.[113] The administration introduced a strategic framework called the Five-Point Opioid Strategy, which includes providing access recovery services, increasing the availability of reversing agents for overdose, funding opioid misuse and pain research, changing treatments of people managing pain, and updating public health reports related to combating opioid drug misuse.[113][114] The US epidemic in the 2000s is related to a number of factors.[16] Rates of opioid use and dependency vary by age, sex, race, and socioeconomic status.[16] With respect to race the discrepancy in deaths is thought to be due to an interplay between physician prescribing and lack of access to healthcare and certain prescription drugs.[16] Men are at higher risk for opioid use and dependency than women,[115][116] and men also account for more opioid overdoses than women, although this gap is closing.[115] Women are more likely to be prescribed pain relievers, be given higher doses, use them for longer durations, and may become dependent upon them faster.[117] Deaths due to opioid use also tend to skew at older ages than deaths from use of other illicit drugs.[116][118][119] This does not reflect opioid use as a whole, which includes individuals in younger age demographics. Overdoses from opioids are highest among individuals who are between the ages of 40 and 50,[119] in contrast to heroin overdoses, which are highest among individuals who are between the ages of 20 and 30.[118] 21- to 35-year-olds represent 77% of individuals who enter treatment for opioid use disorder,[120] however, the average age of first-time use of prescription painkillers was 21.2 years of age in 2013.[121] Among the middle class means of acquiring funds have included Elder financial abuse through a vulnerability of financial transactions of selling items and international dealers noticing a lack of enforcement in their transaction scams throughout the Caribbean.[122] In 2018, the Massachusetts Supreme Judicial Court found that a probationer with opioid use disorder could be detained for a parole violation after she tested positive for fentanyl.[123][124] * Charts of deaths involving specific opioids and classes of opioids * US yearly deaths from all opioid drugs. Included in this number are opioid analgesics, along with heroin and illicit synthetic opioids.[125] * US yearly deaths involving other synthetic opioids, predominately Fentanyl.[125] * US yearly deaths involving prescription opioids. Non-methadone synthetics is a category dominated by illegally acquired fentanyl, and has been excluded.[125] * US yearly overdose deaths involving heroin.[125] ## History[edit] Opiate misuse has been recorded at least since 300 BC. Greek mythology describes Nepenthe (Greek “free from sorrow”) and how it was used by the hero of the Odyssey. Opioids have been used in the Near East for centuries. The purification of and isolation of opiates occurred in the early 19th century.[28] Levacetylmethadol was previously used to treat opioid dependence. In 2003 the drug's manufacturer discontinued production. There are no available generic versions. LAAM produced long-lasting effects, which allowed the person receiving treatment to visit a clinic only three times per week, as opposed to daily as with methadone.[126] In 2001, levacetylmethadol was removed from the European market due to reports of life-threatening ventricular rhythm disorders.[127] In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.[128] ## See also[edit] * Benzodiazepine withdrawal syndrome * Doctor shopping * Hyperkatifeia, hypersensitivity to emotional distress in the context of opioid abuse * Physical dependence * Post-acute-withdrawal syndrome * Prescription drug abuse ## References[edit] 1. ^ a b "FDA approves first buprenorphine implant for treatment of opioid dependence". U.S. Food and Drug Administration (FDA) (Press release). 26 May 2016. Retrieved 16 March 2017. 2. ^ "3 Patient Assessment". Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. 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Eldred, 101 N.E.3d 911 (Mass. 2018). 125. ^ a b c d Overdose Death Rates. By National Institute on Drug Abuse (NIDA). 126. ^ James W. Kalat, Biological Psychology. Cengage Learning. Page 81. 127. ^ EMEA 19 April 2001 EMEA Public Statement on the Recommendation to Suspend the Marketing Authorisation for Orlaam (Levacetylmethadol) in the European Union 128. ^ US FDA Safety Alerts: Orlaam (levomethadyl acetate hydrochloride) Page Last Updated: 20 August 2013 Archived 18 January 2017 at the Wayback Machine ## External links[edit] * Heroin information from the National Institute on Drug Abuse * Opioid information at Opioids.Net * Opioid Dependence Treatment and Guidelines * Opioid Risk Tool (ORT) for Narcotic Abuse Classification D * ICD-10: F11.2 * ICD-9-CM: 304.0 * MeSH: D009293 * v * t * e Psychoactive substance-related disorder General * SID * Substance intoxication / Drug overdose * Substance-induced psychosis * Withdrawal: * Craving * Neonatal withdrawal * Post-acute-withdrawal syndrome (PAWS) * SUD * Substance abuse / Substance-related disorders * Physical dependence / Psychological dependence / Substance dependence Combined substance use * SUD * Polysubstance dependence * SID * Combined drug intoxication (CDI) Alcohol SID Cardiovascular diseases * Alcoholic cardiomyopathy * Alcohol flush reaction (AFR) Gastrointestinal diseases * Alcoholic liver disease (ALD): * Alcoholic hepatitis * Auto-brewery syndrome (ABS) Endocrine diseases * Alcoholic ketoacidosis (AKA) Nervous system diseases * Alcohol-related dementia (ARD) * Alcohol intoxication * Hangover Neurological disorders * Alcoholic hallucinosis * Alcoholic polyneuropathy * Alcohol-related brain damage * Alcohol withdrawal syndrome (AWS): * Alcoholic hallucinosis * Delirium tremens (DTs) * Fetal alcohol spectrum disorder (FASD) * Fetal alcohol syndrome (FAS) * Korsakoff syndrome * Positional alcohol nystagmus (PAN) * Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis) * Wernicke encephalopathy (WE) Respiratory tract diseases * Alcohol-induced respiratory reactions * Alcoholic lung disease SUD * Alcoholism (alcohol use disorder (AUD)) * Binge drinking Caffeine * SID * Caffeine-induced anxiety disorder * Caffeine-induced sleep disorder * Caffeinism * SUD * Caffeine dependence Cannabis * SID * Cannabis arteritis * Cannabinoid hyperemesis syndrome (CHS) * SUD * Amotivational syndrome * Cannabis use disorder (CUD) * Synthetic cannabinoid use disorder Cocaine * SID * Cocaine intoxication * Prenatal cocaine exposure (PCE) * SUD * Cocaine dependence Hallucinogen * SID * Acute intoxication from hallucinogens (bad trip) * Hallucinogen persisting perception disorder (HPPD) Nicotine * SID * Nicotine poisoning * Nicotine withdrawal * SUD * Nicotine dependence Opioids * SID * Opioid overdose * SUD * Opioid use disorder (OUD) Sedative / hypnotic * SID * Kindling (sedative–hypnotic withdrawal) * benzodiazepine: SID * Benzodiazepine overdose * Benzodiazepine withdrawal * SUD * Benzodiazepine use disorder (BUD) * Benzodiazepine dependence * barbiturate: SID * Barbiturate overdose * SUD * Barbiturate dependence Stimulants * SID * Stimulant psychosis * amphetamine: SUD * Amphetamine dependence Volatile solvent * SID * Sudden sniffing death syndrome (SSDS) * Toluene toxicity * SUD * Inhalant abuse * v * t * e Opioid receptor modulators MOR * Agonists (abridged; see here for a full list): 3-HO-PCP * 7-Acetoxymitragynine * 7-Hydroxymitragynine * ψ-Akuammigine * α-Chlornaltrexamine * α-Narcotine * Acetyldihydrocodeine * Acetylfentanyl * Acrylfentanyl * Adrenorphin (metorphamide) * AH-7921 * Akuammicine * Akuammidine * Alfentanil * Anileridine * Apparicine * β-Endorphin * BAM-12P * BAM-18P * BAM-22P * Benzhydrocodone * Benzylmorphine * Bezitramide * Biphalin * BU08070 * Buprenorphine * Butorphan * Butorphanol * Butyrfentanyl * BW373U86 * Carfentanil * Casokefamide * Cebranopadol * Chloroxymorphamine * Codeine * DADLE * DAMGO (DAGO) * Dermorphin * Desmetramadol (desmethyltramadol) * Desomorphine * Dextromoramide * Dextropropoxyphene (propoxyphene) * Dezocine * Dimenoxadol * Dimethylaminopivalophenone * Eluxadoline * Diamorphine (heroin) * Dihydrocodeine * Dihydroetorphine * Dihydromorphine * Dinalbuphine sebacate * Diphenoxylate * Dipipanone * Dynorphin A * Embutramide * Endomorphin-1 * Endomorphin-2 * Eseroline * Ethylmorphine * Etorphine * Fentanyl * Fluorophen * Frakefamide * Furanylfentanyl * Hemorphin-4 * Herkinorin * Hodgkinsine * Hydrocodone * Hydromorphinol * Hydromorphone * IBNtxA * Ketamine * Ketobemidone * Kratom * Laudanosine * Lefetamine * Leu-enkephalin * Levacetylmethadol * Levomethorphan * Levorphanol * Lexanopadol * Loperamide * Loxicodegol * LS-115509 * Matrine * Meptazinol * Met-enkephalin (metenkefalin) * Methadone * Metkefamide * Metopon * Mitragynine * Mitragynine pseudoindoxyl * Morphiceptin * Morphine * Nalbuphine * NalBzOH * Nalmexone * Naltalimide * Neopine * NFEPP * Nicocodeine * Nicodicodine * Nicomorphine * NKTR-181 * Norketamine * Octreotide * Oliceridine * OM-3-MNZ * Oripavine * Oxycodone * Oxymorphazone * Oxymorphonazine * Oxymorphone * Oxymorphone phenylhydrazone * OxyPNPH * Papaver somniferum (opium) * Pentazocine * Pericine * Pethidine (meperidine) * Phenazocine * Phencyclidine * Piminodine * Piritramide * PL-017 * Prodine * Propiram * PZM21 * Racemethorphan * Racemorphan * Remifentanil * Salsolinol * SC-17599 * Sinomenine * Sufentanil * Tapentadol * Tetrahydropapaveroline * TH-030418 * Thebaine * Thienorphine * Tianeptine * Tilidine * Tramadol * Trimebutine * TRIMU 5 * TRV734 * Tubotaiwine * U-47700 * Valorphin * Viminol * Xorphanol * PAMs: BMS-986121 * BMS-986122 * Antagonists: (3S,4S)-Picenadol * 2-(S)-N,N-(R)-Viminol * 3CS-nalmefene * 4-Caffeoyl-1,5-quinide * 4′-Hydroxyflavanone * 4',7-Dihydroxyflavone * 6β-Naltrexol * 6β-Naltrexol-d4 * 18-MC * α-Gliadin * β-Chlornaltrexamine * β-Funaltrexamine * Akuammine * Alvimopan * AM-251 * Apigenin * AT-076 * Axelopran * Bevenopran * Catechin * Catechin gallate * Clocinnamox * CTAP * CTOP * Cyclofoxy * Cyprodime * Diacetylnalorphine * Diprenorphine * ECG * EGC * Epicatechin * Eptazocine * Gemazocine * Ginsenoside R * Hyperoside * Ibogaine * Levallorphan * Lobeline * LY-255582 * LY-2196044 * Methocinnamox * Methylnaltrexone * Methylsamidorphan chloride * Naldemedine * Nalmefene * Nalodeine (N-allylnorcodeine) * Nalorphine * Nalorphine dinicotinate * Naloxazone * Naloxegol * Naloxol * Naloxonazine * Naloxone * Naltrexazone * Naltrexonazine * Naltrexone * Naltrindole * Naringenin * Noribogaine * Oxilorphan * Pawhuskin A * Rimonabant * Quadazocine * Samidorphan * Taxifolin * Unknown/unsorted: Cannabidiol * Coronaridine * Cyproterone acetate * Dihydroakuuamine * Tabernanthine * Tetrahydrocannabinol DOR * Agonists: 3CS-nalmefene * 6'-GNTI * 7-SIOM * ADL-5747 (PF-04856881) * ADL-5859 * Alazocine (SKF-10047) * Amoxapine * AR-M100390 (ARM390) * AZD2327 * β-Endorphin * BAM-18P * Biphalin * BU-48 * Butorphan * Butorphanol * BW373U86 * Casokefamide * Cebranopadol * Codeine * Cyclazocine * DADLE * Deltorphin A * Deltorphin I * Deltorphin II * Desmethylclozapine * Desmetramadol (desmethyltramadol) * Dezocine * Diamorphine (heroin) * Dihydroetorphine * Dihydromorphine * DPDPE * DPI-221 * DPI-3290 * DSLET * Ethylketazocine * Etorphine * Fentanyl * FIT * Fluorophen * Hemorphin-4 * Hydrocodone * Hydromorphone * Ibogaine * Isomethadone * JNJ-20788560 * KNT-127 * Kratom * Laudanosine * Leu-enkephalin * Levomethorphan * Levorphanol * Lexanopadol * Lofentanil * Met-enkephalin (metenkefalin) * Metazocine * Metkefamide * Mitragynine * Mitragynine pseudoindoxyl * Morphine * N-Phenethyl-14-ethoxymetopon * Norbuprenorphine * NalBzOH * Oripavine * Oxycodone * Oxymorphone * Pethidine (meperidine) * Proglumide * Racemethorphan * Racemorphan * RWJ-394674 * Samidorphan * SB-235863 * SNC-80 * SNC-162 * TAN-67 (SB-205,607) * TH-030418 * Thebaine * Thiobromadol (C-8813) * Tonazocine * Tramadol * TRV250 * Xorphanol * Zenazocine * Antagonists: 4',7-Dihydroxyflavone * 5'-NTII * 6β-Naltrexol * 6β-Naltrexol-d4 * α-Santolol * β-Chlornaltrexamine * Apigenin * AT-076 * Axelopran * Bevenopran * BNTX * Catechin * Catechin gallate * Clocinnamox * Diacetylnalorphine * Diprenorphine * ECG * EGC * Eluxadoline * Epicatechin * ICI-154129 * ICI-174864 * LY-255582 * LY-2196044 * Methylnaltrexone * Methylnaltrindole * N-Benzylnaltrindole * Nalmefene * Nalorphine * Naltrexone * Naltriben * Naltrindole * Naloxone * Naringenin * Noribogaine * Pawhuskin A * Quadazocine * SDM25N * SoRI-9409 * Taxifolin * Thienorphine * Unknown/unsorted: 18-MC * Cannabidiol * Coronaridine * Cyproterone acetate * Tabernanthine * Tetrahydrocannabinol KOR * Agonists: 3CS-nalmefene * 6'-GNTI * 8-CAC * 18-MC * 14-Methoxymetopon * β-Chlornaltrexamine * β-Funaltrexamine * Adrenorphin (metorphamide) * Akuuamicine * Alazocine (SKF-10047) * Allomatrine * Apadoline * Asimadoline * BAM-12P * BAM-18P * BAM-22P * Big dynorphin * Bremazocine * BRL-52537 * Butorphan * Butorphanol * BW373U86 * Cebranopadol * Ciprefadol * CR665 * Cyclazocine * Cyclorphan * Cyprenorphine * Desmetramadol (desmethyltramadol) * Diamorphine (heroin) * Diacetylnalorphine * Difelikefalin * Dihydroetorphine * Dihydromorphine * Dinalbuphine sebacate * Diprenorphine * Dynorphin A * Dynorphin B (rimorphin) * Eluxadoline * Enadoline * Eptazocine * Erinacine E * Ethylketazocine * Etorphine * Fedotozine * Fentanyl * Gemazocine * GR-89696 * GR-103545 * Hemorphin-4 * Herkinorin * HS665 * Hydromorphone * HZ-2 * Ibogaine * ICI-199,441 * ICI-204,448 * Ketamine * Ketazocine * Laudanosine * Leumorphin (dynorphin B-29) * Levallorphan * Levomethorphan * Levorphanol * Lexanopadol * Lofentanil * LPK-26 * Lufuradom * Matrine * MB-1C-OH * Menthol * Metazocine * Metkefamide * Mianserin * Mirtazapine * Morphine * Moxazocine * MR-2034 * N-MPPP * Nalbuphine * NalBzOH * Nalfurafine * Nalmefene * Nalodeine (N-allylnorcodeine) * Nalorphine * Naltriben * Niravoline * Norbuprenorphine * Norbuprenorphine-3-glucuronide * Noribogaine * Norketamine * Oripavine * Oxilorphan * Oxycodone * Pentazocine * Pethidine (meperidine) * Phenazocine * Proxorphan * Racemethorphan * Racemorphan * RB-64 * Salvinorin A (salvia) * Salvinorin B ethoxymethyl ether * Salvinorin B methoxymethyl ether * Samidorphan * Spiradoline (U-62,066) * TH-030418 * Thienorphine * Tifluadom * Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline) * U-50488 * U-54,494A * U-69,593 * Xorphanol * Antagonists: 4′-Hydroxyflavanone * 4',7-Dihydroxyflavone * 5'-GNTI * 6'-GNTI * 6β-Naltrexol * 6β-Naltrexol-d4 * β-Chlornaltrexamine * Buprenorphine/samidorphan * Amentoflavone * ANTI * Apigenin * Arodyne * AT-076 * Aticaprant * Axelopran * AZ-MTAB * Binaltorphimine * BU09059 * Buprenorphine * Catechin * Catechin gallate * CERC-501 (LY-2456302) * Clocinnamox * Cyclofoxy * Dezocine * DIPPA * EGC * ECG * Epicatechin * Hyperoside * JDTic * LY-255582 * LY-2196044 * LY-2444296 * LY-2459989 * LY-2795050 * MeJDTic * Methylnaltrexone * ML190 * ML350 * MR-2266 * N-Fluoropropyl-JDTic * Naloxone * Naltrexone * Naltrindole * Naringenin * Norbinaltorphimine * Noribogaine * Pawhuskin A * PF-4455242 * RB-64 * Quadazocine * Taxifolin * UPHIT * Zyklophin * Unknown/unsorted: Akuammicine * Akuammine * Coronaridine * Cyproterone acetate * Dihydroakuuamine * Ibogamine * Tabernanthine NOP * Agonists: (Arg14,Lys15)Nociceptin * ((pF)Phe4)Nociceptin(1-13)NH2 * (Phe1Ψ(CH2-NH)Gly2)Nociceptin(1-13)NH2 * Ac-RYYRWK-NH2 * Ac-RYYRIK-NH2 * BU08070 * Buprenorphine * Cebranopadol * Dihydroetorphine * Etorphine * JNJ-19385899 * Levomethorphan * Levorphanol * Levorphanol * Lexanopadol * MCOPPB * MT-7716 * NNC 63-0532 * Nociceptin (orphanin FQ) * Nociceptin (1-11) * Nociceptin (1-13)NH2 * Norbuprenorphine * Racemethorphan * Racemorphan * Ro64-6198 * Ro65-6570 * SCH-221510 * SCH-486757 * SR-8993 * SR-16435 * TH-030418 * Antagonists: (Nphe1)Nociceptin(1-13)NH2 * AT-076 * BAN-ORL-24 * BTRX-246040 (LY-2940094) * J-113,397 * JTC-801 * NalBzOH * Nociceptin (1-7) * Nocistatin * SB-612,111 * SR-16430 * Thienorphine * Trap-101 * UFP-101 Unsorted * β-Casomorphins * Amidorphin * BAM-20P * Cytochrophin-4 * Deprolorphin * Gliadorphin (gluteomorphin) * Gluten exorphins * Hemorphins * Kava constituents * MEAGL * MEAP * NEM * Neoendorphins * Nepetalactone (catnip) * Peptide B * Peptide E * Peptide F * Peptide I * Rubiscolins * Soymorphins Others * Enkephalinase inhibitors: Amastatin * BL-2401 * Candoxatril * D -Phenylalanine * Dexecadotril (retorphan) * Ecadotril (sinorphan) * Kelatorphan * Racecadotril (acetorphan) * RB-101 * RB-120 * RB-3007 * Opiorphan * Selank * Semax * Spinorphin * Thiorphan * Tynorphin * Ubenimex (bestatin) * Propeptides: β-Lipotropin (proendorphin) * Prodynorphin * Proenkephalin * Pronociceptin * Proopiomelanocortin (POMC) * Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer) See also: Receptor/signaling modulators • Signaling peptide/protein receptor modulators * v * t * e Reinforcement disorders: Addiction and Dependence Addiction Drug * Alcohol * Amphetamine * Cocaine * Methamphetamine * Methylphenidate * Nicotine * Opioid Behavioral * Financial * Gambling * Shopping * Palatable food * Sex-related * Intercourse * Pornography * Internet-related * Internet addiction disorder * Internet sex addiction * Video game addiction * Digital media addictions Cellular mechanisms * Transcriptional * ΔFosB * c-Fos * Cdk5 * CREB * GluR2 * NF-κB * Epigenetic * G9a * G9a-like protein * HDAC1 * HDAC2 * HDAC3 * HDAC4 * HDAC5 * HDAC9 * HDAC10 * SIRT1 * SIRT2 * ... Dependence Concepts * Physical dependence * Psychological dependence * Withdrawal Disorders * Drugs * Alcoholism * Amphetamine * Barbiturate * Benzodiazepine * Caffeine * Cannabis * Cocaine * Nicotine * Opioid * Non-drug stimuli * Tanning dependence Treatment and management Detoxification * Alcohol detoxification * Drug detoxification Behavioral therapies * Cognitive behavioral therapy * Relapse prevention * Contingency management * Community reinforcement approach and family training * Motivational enhancement therapy * Motivational interviewing * Motivational therapy * Physical exercise Treatment programs * Drug rehab * Residential treatment center * Heroin-assisted treatment * Intensive outpatient program * Methadone maintenance * Smoking cessation * Nicotine replacement therapy * Tobacco cessation clinics in India * Twelve-step program Support groups * Addiction recovery groups * List of twelve-step groups Harm reduction * Category:Harm reduction * Drug checking * Reagent testing * Low-threshold treatment programs * Managed alcohol program * Moderation Management * Needle exchange program * Responsible drug use * Stimulant maintenance * Supervised injection site * Tobacco harm reduction See also * Addiction medicine * Allen Carr * Category:Addiction * Discrimination against drug addicts * Dopamine dysregulation syndrome * Cognitive control * Inhibitory control * Motivational salience * Incentive salience * Sober companion * Category * v * t * e Treatment of drug dependence (N07B) Nicotine dependence * Bupropion * Cytisine * Lobeline * Mecamylamine * Varenicline * AA (Clonidine) Alcohol dependence * AD inhibitor (Disulfiram * Calcium carbimide * Hydrogen cyanamide) * Acamprosate * Opioid antagonists * Naltrexone * Nalmefene) * κ-Opioid receptor antagonists * Aticaprant * Topiramate * AA (Clonidine) * Baclofen * Phenibut Opioid dependence * AA (Clonidine * Lofexidine) * Ibogaine * Opioids * Buprenorphine (+naloxone) * Levacetylmethadol * Methadone * Dihydrocodeine * Dihydroetorphine * Hydromorphone (extended-release) * Morphine (extended-release) * Opioid antagonists (Naltrexone * Nalmefene) Benzodiazepine dependence * AA (Clonidine) * Benzodiazepines (Diazepam * Lorazepam * Chlordiazepoxide * Oxazepam) * Barbiturates (Phenobarbital) Research Salvia divinorum * v * t * e Unnecessary health care Causes * Direct-to-consumer advertising * Overscreening * Overdiagnosis * Fee-for-service * Defensive medicine * Unwarranted variation * Overmedication * Overmedicalization * Prescription cascade * Quaternary prevention * Disease mongering * Political abuse of psychiatry Overused health care * Caesarean delivery on maternal request * Antibiotic misuse * Benzodiazepine use disorder * Effects of long-term benzodiazepine use * Opioid use disorder * Psychoactive drug * Proton-pump inhibitor * Polypharmacy * treatment of incidentaloma Tools and Situations * Deprescribing * Choosing Wisely * Medication discontinuation * Withdrawal syndrome * Antidepressant discontinuation syndrome * Benzodiazepine withdrawal syndrome Works about unnecessary health care * Overtreated * The Treatment Trap * Selling Sickness * Overdosed America *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor

Opioid use disorder

c0029095

wikipedia

https://en.wikipedia.org/wiki/Opioid_use_disorder

{"mesh": ["D009293"], "umls": ["C0029095"], "wikidata": ["Q1639178"]}

## Description Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by utero-vaginal atresia in an otherwise phenotypically normal female with a normal 46,XX karyotype. Anomalies of the genital tract range from upper vaginal atresia to total mullerian agenesis with urinary tract abnormalities. It has an incidence of approximately 1 in 5,000 newborn girls (Cheroki et al., 2006). The abnormality of sexual development in MRKH syndrome is the same as that in the MURCS association (601076), in which cervicothoracic somite anomalies, unilateral renal agenesis, and conductive deafness are also seen. Mullerian aplasia and hyperandrogenism (158330) is caused by mutation in the WNT4 gene (603490). Familial cases of unilateral or bilateral renal agenesis in combination with mullerian anomalies have also been reported (see urogenital adysplasia, 191830). Clinical Features The features, in addition to congenital absence of the vagina, are normal female secondary sexual characteristics, rudimentary uterus in the form of bilateral and noncanaliculated muscular buds, normal tubes and ovaries and normal endocrine and cytogenetic evaluations. Anger et al. (1966) reported 3 affected sisters. Phaneuf (1947) described the malformation in 2 pairs of sisters whose mothers were sisters. Bryan et al. (1949) mentioned that in one of their 100 cases a sister had congenital absence of the vagina and 2 had a sister with primary amenorrhea. Jones and Mermut (1972) concluded that most of the earlier reported cases, except those of Anger et al. (1966), were instances of testicular feminization (300068). They reported 2 affected sisters. Karyotype was normal. Las Casas dos Santos (1888) reported familial cases and referred to a report by Squarey of 3 sisters who had a maternal aunt with no menstruation and 3 other sterile aunts; to a report by Phillips of 2 sisters with congenital absence of the uterus and vagina (with no supporting information) and to a report by Hauff of a person with no uterus, tubes or ovaries, whose sister had 2 daughters with the same condition. The last is clearly testicular feminization, because the author had an opportunity to look for the ovaries (Jones, 1972). Wulfsberg and Grigbsy (1990) reported the Rokitansky sequence in association with facioauriculovertebral sequence (Goldenhar syndrome; 164210) and found reports of 3 other such cases (Rapin and Ruben, 1976; Willemsen, 1982; Winer-Muram et al., 1984). Shokeir (1978) described 18 unrelated females, aged 15 to 28, with aplasia of the mullerian duct derivatives. Their complaints were amenorrhea and difficulty or pain on attempting sexual intercourse; absence of the vagina and failure to palpate the uterus rectally were features in all. Female sexual identification, libido, and female secondary sexual characteristics, as well as stature, intellect, hearing, and vision, were normal. Laparoscopy showed absent uterus, absent or rudimentary tubes, and normal ovaries. Of the eighteen, 14 had affected relatives. The pedigree pattern was consistent with female-limited autosomal dominant inheritance. The disorder was transmitted through normal males. Because of the observation that female rats showed delayed vaginal opening and reduced oocyte number when born to mothers fed on a high-galactose diet (Chen et al., 1981), Cramer et al. (1987) analyzed blood for transferase in 4 mother-daughter pairs in which the daughter had mullerian aplasia. In 2 of the mother-daughter pairs, they found deficiency of transferase. One was a Duarte heterozygote (both mother and daughter); a sister did not have mullerian aplasia, but had premature menopause. In the second pair, the Los Angeles type of transferase deficiency was found in heterozygous state in the mother and daughter. In that instance, the mother was a very heavy milk consumer. See galactosemia (230400). Bau et al. (1994) reported the case of a 32-year-old woman with the Rokitansky sequence in association with bilateral femoral hypoplasia (proximal femoral focal deficiency). She had a short vagina and by ultrasound absence of the uterus with normal kidneys. Guerrier et al. (2006) reviewed the clinical features of the MRKH syndrome and MURCS association phenotypes and discussed genetic hypotheses. Morcel et al. (2007) reviewed the clinical features and management of MRKH syndrome. ### Urogenital Adysplasia Buchta et al. (1973) described a woman with unilateral renal agenesis who gave birth to 2 children with the same condition and a third child with bilateral renal agenesis. Another female family member lacked a left kidney and fallopian tube and had a uterus bicornis with normal right fallopian tube. The elder of 2 daughters with unilateral renal aplasia had primary amenorrhea due to vaginal atresia with absence of the fallopian tubes and uterus (Opitz, 1987). Buchta et al. (1973) postulated a relationship between renal adysplasia and vaginal atresia, also known as Mayer-Rokitansky-Kuster syndrome. Knudsen et al. (1979) reported a 38-year-old man with unilateral renal agenesis and an ipsilateral seminal vesicle cyst whose sister had embryologically analogous malformations, Gartner duct cyst, bicornuated uterus, and renal agenesis. Schimke and King (1980) observed 3-generation transmission of renal agenesis-dysgenesis with uterine anomaly. The proband was found on work-up, prompted by premarital examination, to have a didelphic uterus with a blind-ending left vaginal pouch, and absent left kidney. The woman subsequently gave birth to a premature female infant who died soon after birth from pulmonary insufficiency. The infant had dolichocephaly, low-set ears, and deformed nose. Autopsy showed pulmonary hypoplasia and 'nearly total renal agenesis.' The vagina, uterus, and Fallopian tubes were grossly normal. The proband's father had unilateral renal agenesis. Schimke and King (1980) suggested that developmental defects in the mesonephric and paramesonephric ducts may have a common genetic basis. They suggested the designation 'hereditary urogenital adysplasia' for the combination of anomalies of the mullerian duct with developmental errors of the urinary tract. Often the concurrence of such defects is poorly documented, seemingly because of concentration on one to the exclusion of the other. Battin et al. (1993) reported a family with unilateral or bilateral renal agenesis in combination with mullerian anomalies, such as vaginal atresia. The family provided support for an autosomal dominant pattern of inheritance with incomplete penetrance and variable expressivity in hereditary renal adysplasia associated with mullerian defects. Drummond et al. (2008) studied 6 Brazilian 46,XX patients with the MRKH defect, 2 of whom were sisters. All had normal secondary sexual characteristics, no clinical signs of hyperandrogenism, and rudimentary uterus and upper vaginal atresia on pelvic ultrasound; 2 patients also had unilateral renal agenesis, but none had skeletal or other associated malformations. Androgen levels were unremarkable in all but 1 patient, who had an elevated basal 17-hydroxyprogesterone level; ACTH-stimulated 17-hydroxyprogesterone levels in that patient were within normal limits, excluding congenital adrenal hyperplasia. Cytogenetics In 2 unrelated women with mullerian duct failure, Taneja et al. (1986) found an identical translocation, t(12;14)(q14;q31). The clinical features were primary amenorrhea with normal appearance, height, behavior, and secondary sexual characteristics, blind-ending vagina, and, by ultrasonography, absent fallopian tubes and uterus. The finding of the translocation suggested that a gene on chromosome 12 or 14 may be involved. Ogata et al. (2000) reported 10 Japanese patients with monosomy of chromosome 10q26. Six patients had urinary anomalies such as vesicoureteral reflux and hypoplastic kidney, and 8 had genital anomalies such as micropenis, hypospadias, cryptorchidism, and hypoplastic labia majora. Microsatellite analysis revealed that hemizygosity for the region distal to D10S186 was shared by cases with urinary anomalies, and that the region distal to D10S1248 was common to cases with genital anomalies. Eight patients had 2 copies of the PAX2 (167409), GFRA1 (601496), and EMX2 (600035) genes on distal 10q. Miyamoto et al. (1997) had found defects of urogenital development in mice lacking Emx2. Molecular Genetics Timmreck et al. (2003) examined the relationship between mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR; 602421) and congenital absence of the uterus and vagina (CAUV). CFTR mutations are associated with congenital bilateral absence of the vas deferens (CBAVD; 277180). CBAVD is caused by a disruption in the vas deferens, a wolffian duct derivative. Because the embryologic development of the mullerian ducts depends directly on the prior normal development of the wolffian ducts, the same gene products may be necessary for normal embryologic development of both ductal systems. Timmreck et al. (2003) studied DNA samples from 25 patients with CAUV for the presence of 33 of the most common CFTR mutations. Two patients were heterozygous for CFTR mutations. One was the W1282X mutation (602421.0022) and the other was the delF508 mutation (602421.0001). The incidence of the 33 CFTR mutations found in the patients with CAUV (8%) was twice that found in the general population (4%), but much less than the incidence of CFTR mutations in men with CBAVD (80%). Timmreck et al. (2003) concluded that it is unlikely that CFTR mutations cause CAUV in females but CAUV in females may be the same disorder as CAUVD in males who do not have CFTR mutations. Cheroki et al. (2006) reported a 17-year-old Brazilian girl who had a rudimentary uterus and vaginal agenesis with normal secondary sexual characteristics in whom they identified a 4-Mb deletion at chromosome 22q11. Additional features included mild to moderate learning disabilities, minor craniofacial anomalies with a long face, prominent nose, short philtrum, and high palate, mild dorso-lumbar scoliosis, and slight increase of the aortic arch. She also had hypothyroidism secondary to Hashimoto thyroiditis. Cheroki et al. (2006) noted that the patient's deletion included loci responsible for DiGeorge syndrome (188400) and velocardiofacial syndrome (192430). Cheroki et al. (2008) further mapped the rearrangement in this patient, revealing that the deletion spanned 2.5 Mb but was interrupted by a small chromosome segment with apparently normal copy number, containing the TBX1 gene (602054). The patient was also noted to have agenesis of the right kidney. Cheroki et al. (2008) performed array CGH on 14 female patients with mullerian aplasia and additional features, including urinary tract anomalies, cardiac and skeletal defects, hearing impairment, and mental retardation. Four (29%) of the 14 patients, 1 of whom was previously studied by Cheroki et al. (2006), were found to have submicroscopic copy number alterations affecting chromosomes 1q21.1, 17q12 (see 614527), 22q11.21, and Xq21.31. The alterations were also present in the unaffected mother of 1 patient, suggesting incomplete penetrance and/or variable expressivity. Cheroki et al. (2008) noted that these findings suggest involvement of previously unknown chromosomal regions in mullerian aplasia, specifically pointing to LHX1 (601999) and KLHL4 (300348) as candidate genes. Bernardini et al. (2009) reported 2 female patients with MRKH syndrome who had identical de novo 1.5-Mb deletions at chromosome 17q12. One was a 20-year-old woman with mildly dysmorphic facial features who presented for evaluation of primary amenorrhea and had complete absence of the uterus and vagina; pelvic MRI showed bilaterally normal ovaries and kidneys. The other patient was a 15-year-old girl who had bilateral renal cysts noted on fetal ultrasound and at 5 years of age had small, multicystic kidneys on ultrasound. At 12 years of age, menarche was complicated by hematocolpos due to agenesis of the upper and middle thirds of the vagina, which was surgically corrected. At laparoscopy, mullerian malformations were seen, including right unicornuate uterus, noncavitating rudimentary left horn, and right hematosalpinx. Growth and psychomotor development were normal in both patients, and both had normal blood glucose levels. Nik-Zainal et al. (2011) performed array CGH on DNA samples from a cohort of 63 individuals with mullerian aplasia and found that 9 (14%) had copy number variants, including 4 with microdeletion at 16p11.2, 4 with microdeletion at 17q12, and 1 with a microdeletion at distal 22q11.2. Microdeletions at 16p11.2 or 17q12 were found in 4 of 38 cases (10.5%) with isolated mullerian aplasia, and at 16p11.2, 17q12, or 22q11.2 in 5 of 25 cases (20%) with syndromic mullerian aplasia. ### Exclusion Studies Clement-Ziza et al. (2005) analyzed the WNT4 gene but identified no mutations in 19 patients with mullerian aplasia from 15 families, 11 of whom had symmetrical uterus abnormalities that are typical of RKH and 6 of whom had asymmetric uterus and renal anomalies; a full uterine survey was not available in 4 cases. Clement-Ziza et al. (2005) concluded that WNT4 is not a major disease-causing gene in MRKH anomaly. Cheroki et al. (2006) failed to find mutations in the WNT4 gene in 25 women with the MRKH anomaly. Biason-Lauber et al. (2007) found no mutations in the WNT4 gene in 5 patients with varying degrees of mullerian abnormalities, 2 of whom also had renal agenesis and dysplasia, and all of whom were negative for mutation in the TCF2 gene (189907). Philibert et al. (2008) found no mutations in the WNT4 gene in 27 adolescent girls with primary amenorrhea, XX karyotype, and mullerian duct abnormalities, who were negative for mutation in the TCF2 gene. In 6 Brazilian 46,XX patients with the MRKH defect, Drummond et al. (2008) sequenced the WNT4 gene but found no nucleotide variation in the coding exons. Bernardini et al. (2009) performed a focused chromosome 17 array CGH analysis in 20 consecutive MRKH patients but detected no abnormalities; direct sequencing of the candidate genes TCF2 and LHX1 (601999) revealed no pathogenic mutations. INHERITANCE \- Autosomal dominant GENITOURINARY External Genitalia (Female) \- Normal external genitalia Internal Genitalia (Female) \- Aplasia of Mullerian duct derivatives \- Dysgenesis of Mullerian duct derivatives \- Congenital absence or severe hypoplasia of the upper two-thirds of vagina \- Congenital absence or severe hypoplasia of uterus \- Aplastic Fallopian tubes (some) \- Functional ovaries ENDOCRINE FEATURES \- Normal female secondary sexual characteristics \- Amenorrhea, primary ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor

MAYER-ROKITANSKY-KUSTER-HAUSER SYNDROME

c0431648

omim

https://www.omim.org/entry/277000

{"mesh": ["C537371"], "omim": ["277000"], "orphanet": ["247775", "3109"], "synonyms": ["Alternative titles", "MRKH SYNDROME", "MULLERIAN APLASIA/DYSGENESIS", "VON MAYER-ROKITANSKY-KUSTER ANOMALY", "MRKH ANOMALY", "MRK ANOMALY", "UTERUS BIPARTITUS SOLIDUS RUDIMENTARIUS CUM VAGINA SOLIDA", "CONGENITAL ABSENCE OF UTERUS AND VAGINA"]}

Meth mouth The mouth of a person with symptoms similar to those caused by long-term use of methamphetamine Meth mouth is severe tooth decay and tooth loss, as well as tooth fracture, acid erosion, and other oral problems, potentially symptomatic of extended use of the drug methamphetamine. The condition is thought to be caused by a combination of side effects of the drug (clenching and grinding of teeth, dry mouth) and lifestyle factors (infrequent oral hygiene, frequent consumption of sugary drinks, as well as neglecting regular dental cleanings and preventive care), which may be present in long-term users. However, the legitimacy of meth mouth as a unique condition has been questioned because of the similar effects of some other drugs on teeth. Images of diseased mouths are often used in anti-drug campaigns. The condition is difficult to treat, and may involve fillings, fluoride to fight tooth decay and drugs that increase saliva for dry mouth, as well as oral hygiene instruction. It can be dangerous for active methamphetamine users to undergo dental surgery because of the cardiac problems that can result from the interaction of local anesthetic with the drug. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Treatment * 4 Uncertainty * 5 Society and culture * 6 See also * 7 References * 8 Bibliography * 9 External links ## Signs and symptoms[edit] Methamphetamine (informally referred to as "meth") is a stimulant drug with a high potential for addiction in its recreational users. It incurs physical and psychological side effects that users find desirable. Other side effects (like bruxism and stimulant psychosis) can result in users neglecting their dental health, eventually leading to advanced tooth decay (caries) and gum infections.[1] Further, a common side effect of stimulant drugs is xerostomia, which accelerates tooth decay.[2] As of 2012[update], methamphetamine is the most discussed illegal drug in dental literature for its extensive effect on users' dental health.[3] The teeth of some methamphetamine users appear to be dark and extensively eroded.[4] The epithet "meth mouth" is the result of these superficial presentations of advanced tooth decay and gum infection. Caries often occur in the cervical regions of teeth, where the tooth surface narrows at the junction of the crown and the root; decay is primarily centered on the buccal (cheek) side of the teeth, and on tooth surfaces that are adjacent to incisors and canines.[3][5] Eventually, the coronal tooth area (near the crown) can be affected by the decay and erosion.[6] The dental caries of meth mouth often progress slowly, perhaps because their advancement is hindered by intermittent hygienic practices.[5] The decay can lead to tooth fractures and severe pain.[3] In some cases, teeth are permanently damaged and must be removed.[5] Along with malnutrition and weight loss, the dental effects of methamphetamine use contribute to the appearance of premature aging seen in some users.[1] Methamphetamine users sometimes experience soreness in the joint of the jaw and dental attrition (tooth wear) due to bruxism, a common side effect of stimulant drugs.[5] This bruxism can occur continuously.[7] Chronic use of the drug might also cause trismus, the inability to open the jaw.[8] The effects of meth mouth are similar to those of Sjögren's syndrome, an autoimmune disease that causes a lack of saliva, which results in tooth decay.[5][6] ## Causes[edit] Powder methamphetamine on tin foil The hypothesized causes of meth mouth are a combination of MA side effects and lifestyle factors which may be present in users: * Dry mouth (xerostomia)[9] * Clenching and grinding of the teeth (bruxism) * Infrequent oral hygiene[9] * Frequent consumption of sugary, fizzy drinks[9] * Caustic nature of methamphetamine[9] The dental effects of long-term methamphetamine use are often attributed to its effects on saliva.[4] The reduction in saliva increases the likelihood of dental caries, enamel erosion, and periodontal disease. Although it is clear that use of the drug decreases saliva, the mechanism by which it does so is unclear. One theory is that the drug causes vasoconstriction (narrowing of the blood vessels) in salivary glands, decreasing salivary flow. This constriction is thought to be due to the activation of alpha-adrenergic receptors by both methamphetamine itself and norepinephrine, the levels of which are dramatically increased by methamphetamine use.[4][7] These factors can be compounded by dehydration, which occurs in many methamphetamine users after drug-induced increases in metabolism.[4] The characteristics of the saliva produced during use of the drug, which includes high protein content, may also contribute to the sensation of dry mouth.[6] Long-term methamphetamine use can cause parafunctional habits, routine actions of a body part that are different than their common use, which can result in tooth wear and exacerbate periodontal diseases.[5] One such habit that may affect the development of meth mouth is bruxism,[5] particularly as the drug's effects wane and stereotypy occurs, a phase that is often referred to as "tweaking".[6] This bruxism may be due to a drug-induced increase in monoamines.[7] Other behaviors of long-term methamphetamine users that may cause or accelerate the symptoms of meth mouth are the failure to pay attention to oral hygiene and excessive food intake during binges, especially sugary foods;[5][6] the drug's users often report strong cravings for sugar and consume large amounts of high-sugar beverages. The altered mental state that accompanies methamphetamine use lasts longer than that of some other common drugs, increasing the amount of time the user engages in drug-induced behavior.[1] Hydrochloric acid is used in methamphetamine's manufacturing process, but academic reviews have not supported the idea that the acid contributes to dental decay.[10][11] Speculation that oral consumption of the drug causes tooth decay by raising the acidity of users' mouths is also unsupported.[5][6] Meth mouth is generally most severe in users who inject the drug, rather than those who smoke, ingest or inhale it.[3] ## Treatment[edit] Rampant caries caused by methamphetamine abuse. The damaging effects of meth mouth on the teeth and gums for the most part are irreversible, although, if treated at an early stage, they can be dramatically reduced through the habitual use of common hygienic practices; Under normal circumstances, the user will not seek a remedy until the damage has already begun to take control causing severe mouth pain and general discomfort.[5] Because many drug users lack the access to dental treatment, due to affordability and poverty, it is important to take medical precautions to prolong the lifespan of the mouth, and health in general. [5] [3] Those who are willing to seek dental treatment should seek professional advice as soon as possible if they are experiencing any painful symptoms relatable to meth mouth from abusing methamphetamine.[12] Providing dental treatment to individuals who use methamphetamine can be dangerous, because the potential combination of local anesthetic and methamphetamine can cause serious heart problems.[13] There is also an increased risk of serious side effects if opioid medications are used in the patient's treatment.[4] Treatment of meth mouth usually attempts to increase the flow of saliva, halt tooth decay, and encourage behavioral changes. Toothpaste with fluoride is very important to the restoration of dental health.[5] Prescription fluoride rinses can adequately treat the condition as well.[13] Sialogogues, drugs that increase the amount of saliva in the mouth, can be used to treat dry mouth and protect against dental health problems. Pilocarpine and cevimeline are sialogogues approved by the Food and Drug Administration (FDA) to treat low salivation caused by Sjögren syndrome and may have the potential to effectively treat dry mouth caused by methamphetamine use.[13] ## Uncertainty[edit] There have not been any controlled studies on meth mouth, and several of its aspects are unclear.[11] Although the condition has been popularized by media coverage and case reports, no systematic studies have been conducted to conclusively tie methamphetamine use to symptoms that are commonly described as meth mouth. There are few ties between dental scholars and those who study drug use, and it can be difficult for dental researchers to find methamphetamine users to study.[14] Whether the drug has a unique effect on dental health has been questioned by a few academics, who note that the long-term use of several other drugs sometimes causes dental problems.[15] Several academic reviews have contradicted this perspective, affirming meth mouth's status as a discrete condition.[3][16][17] In favor of its unique status, these reviews cite the differences between methamphetamine-caused caries and those that occur for other reasons, such as cocaine use,[3][5] as well as the scope of the tooth decay found in some long-term methamphetamine users.[15] ## Society and culture[edit] Although most methamphetamine users lived in Asia in the early 2000s,[18] the use of the drug increased dramatically in other parts of the world in that decade.[14] In areas where use of the drug has become common, meth mouth is often widespread.[1][19] The condition is expensive to treat and has strained public health resources,[20][21] prompting concerns among dental authorities in several countries about the burden of treatment.[22][23] Images of meth mouth are usually considered disturbing and have been used in anti-drug campaigns,[24] even being placed on hoardings/billboards.[25] The condition is often mentioned in media coverage of methamphetamine,[24] and it has been included in media portrayals of drug abuse to demonstrate the scope of the drug's effects or to provoke disgust in the audience.[26][27] Opponents argue that the term is used to negatively stereotype methamphetamine users, and that it is falsely portrayed as inevitable or characteristic.[28] The drama series Breaking Bad, which centres around the production of crystal meth, features a number of minor characters who have meth mouth. The series creator Vince Gilligan has said one of his regrets about the series is that one of the lead characters, Jesse Pinkman, (played by Aaron Paul), had perfect teeth because he felt this was unrealistic, given the amount of meth the character consumed. ## See also[edit] * Faces of Meth ## References[edit] 1. ^ a b c d Winslow, Voorhees & Pehl 2007. 2. ^ "Xerostomia (Dry Mouth)". www.ada.org. Retrieved 2018-08-17. 3. ^ a b c d e f g Hussain, Frare & Berrios 2012. 4. ^ a b c d e Hamamoto & Rhodus 2009, p. 31. 5. ^ a b c d e f g h i j k l m Hamamoto & Rhodus 2009, p. 32. 6. ^ a b c d e f Goodchild & Donaldson 2007, p. 586. 7. ^ a b c Rusyniak 2011. 8. ^ Hamamoto & Rhodus 2009, pp. 31–32. 9. ^ a b c d De-Carolis, C; Boyd, GA; Mancinelli, L; Pagano, S; Eramo, S (1 March 2015). "Methamphetamine abuse and "meth mouth" in Europe". Medicina Oral, Patologia Oral y Cirugia Bucal. 20 (2): e205–10. doi:10.4317/medoral.20204. PMC 4393984. PMID 25662544. 10. ^ Goodchild & Donaldson 2007, p. 585. 11. ^ a b Karch 2008, p. 291. 12. ^ Hamamoto & Rhodus 2009, p. 30. 13. ^ a b c Hamamoto & Rhodus 2009, p. 33. 14. ^ a b Shetty et al. 2010. 15. ^ a b Goodchild & Donaldson 2007, p. 585–86. 16. ^ Goodchild & Donaldson 2007, p. 589. 17. ^ Hamamoto & Rhodus 2009, p. 34. 18. ^ Saini et al. 2005, p. 189. 19. ^ Treadwell, Northbridge & Bethea 2007, p. 337. 20. ^ Davey 2005. 21. ^ Kinkead & Romboy 2005. 22. ^ Naidoo 2009. 23. ^ Herald Sun & July 30, 2007. 24. ^ a b Weisheit & White 2009, p. 65. 25. ^ Verini 2009. 26. ^ Littmann 2012, p. 160. 27. ^ Billen 2009. 28. ^ Sullum, Jacob (20 February 2014). "Hyperbole Hurts: The Surprising Truth About Methamphetamine". Forbes. Retrieved 23 February 2014. ## Bibliography[edit] Books * Treadwell, Henry M.; Northbridge, Mary E.; Bethea, Traci N. (2007). "Building the Case for Oral Health Care for Prisoners". In Greifinger, Robert B. (ed.). Public Health Behind Bars: From Prisons to Communities. New York: Springer Science+Business Media. ISBN 978-0-387-71694-7.CS1 maint: ref=harv (link) * Karch, Steven B. (2008). Karch's Pathology of Drug Abuse (Fourth ed.). Boca Raton: CRC Press. ISBN 978-0-8493-7880-5.CS1 maint: ref=harv (link) * Littmann, Greg (2012). George Reish; David Koepsell; Robert Arp (eds.). Breaking Bad and Philosophy. Open Court Publishing. ISBN 978-0-8126-9764-3.CS1 maint: ref=harv (link) * Weisheit, Ralph; White, William L. (2009). Methamphetamine: Its History, Pharmacology, and Treatment. Center City, Minn: Hazelden Publishing. ISBN 978-1-59285-717-3.CS1 maint: ref=harv (link) Journals * Winslow, Bradford; Voorhees, Kenton; Pehl, Katherine (2007). "Methamphetamine Abuse". American Family Physician. 76 (8): 1169–1174. PMID 17990840.CS1 maint: ref=harv (link) * Goodchild, Jason; Donaldson, Mark (2007). "Methamphetamine Abuse and Dentistry: A Review of the Literature and Presentation of a Clinical Case". Quintessence International. 38 (7): 583–590. PMID 17694215.CS1 maint: ref=harv (link) * Hamamoto, D. T.; Rhodus, N. L. (2009). "Methamphetamine Abuse and Dentistry". Oral Diseases. 15 (1): 27–37. doi:10.1111/j.1601-0825.2008.01459.x. PMID 18992021.CS1 maint: ref=harv (link) * Hussain, Fahmida; Frare, Robert; Berrios, Karen (2012). "Drug Abuse Identification and Pain Management in Dental Patients: A Case Study and Literature Review". General Dentistry. 60 (4): 334–345. PMID 22782046.CS1 maint: ref=harv (link) * Rusyniak, Daniel (2011). "Neurologic Manifestations of Chronic Methamphetamine Abuse". Neurologic Clinics. 29 (3): 641–655. doi:10.1016/j.ncl.2011.05.004. PMC 3148451. PMID 21803215.CS1 maint: ref=harv (link) * Saini, Tarnjit; Edwardsa, Paul; Kimmesa, Nicole; Carrolla, Lucinda; Shanera, John; Dowdb, Frank (2005). "Etiology of Xerostomia and Dental Caries among Methamphetamine Abusers". Oral Health & Preventative Dentistry. 3 (3): 189–195. PMID 16355653. * Shetty, Vivek; Mooney, Larissa; Zigler, Corwin; Belin, Thomas; Murphy, Debra; Rawson, Richard (2010). "The Relationship Between Methamphetamine Use and Increased Dental Disease". The Journal of the American Dental Association. 141 (3): 307–318. doi:10.14219/jada.archive.2010.0165. PMC 2947197. PMID 20194387. Newspapers * "The Tooth on Drugs". Herald Sun. July 30, 2007. Retrieved September 12, 2012. * Billen, Andrew (August 10, 2009). "Louis Theroux: The City Addicted to Crystal Meth". The Times. Retrieved September 30, 2012.CS1 maint: ref=harv (link) * Davey, Monica (June 11, 2005). "Grisly Effect of One Drug: 'Meth Mouth'". The New York Times. Retrieved May 6, 2012.CS1 maint: ref=harv (link) * Kinkead, Lucinda Dillon; Romboy, Dennis (June 12, 2005). "Meth Mouth: Ugly Legacy of Drug is Taxing Utah Jail, Prison Medical Budgets". Deseret News. Retrieved August 31, 2012.CS1 maint: ref=harv (link) * Naidoo, Yugendree (August 3, 2009). "Dentists Face Tik Toothache". West Cape News. Retrieved September 11, 2012.CS1 maint: ref=harv (link) * Verini, James (May 1, 2009). "Meth Mouth: Tom Siebel's Brash Anti-Crystal Campaign". Fast Company. Retrieved August 28, 2012.CS1 maint: ref=harv (link) ## External links[edit] Wikimedia Commons has media related to Meth mouth. * American Dental Association Overview of Meth Mouth * Meth Mouth Image Gallery at CBSNews.com * v * t * e Methamphetamine Enantiomers * Dextromethamphetamine * Levomethamphetamine Neuropharmacology Biomolecular targets * TAAR1 (agonist) * σ1R (agonist) * σ2R (agonist) * α2A adrenoceptor (agonist) * α2B adrenoceptor (agonist) * α2C adrenoceptor (agonist) * MAO (competitive inhibitor) Inhibited transporters * DAT * NET * SERT * VMAT1 * VMAT2 * EAAT1 * EAAT2 * SLC22A3 * SLC22A5 Health * Amphetamine dependence * Meth mouth * Prenatal methamphetamine exposure History and culture * Amphetamine * Crystal Darkness * Crystal Meth Anonymous * Faces of Meth * History and culture of amphetamines * Montana Meth Project * No More Sunsets * Party and play * Rolling meth lab * Ya ba Law * Legal status * Combat Methamphetamine Epidemic Act of 2005 * Comprehensive Methamphetamine Control Act of 1996 * Illinois Methamphetamine Precursor Control Act Ethnicity and nationality * United States * Native Americans * Australia * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor

Meth mouth

None

wikipedia

https://en.wikipedia.org/wiki/Meth_mouth

{"wikidata": ["Q956605"]}

## Description Malpositioning, or ectopic placement, of teeth is believed to result from a disturbance of the tooth developmental structure. Various forms of the disorder tend to be associated with one another and with hypodontia. It is important to recognize any associations of tooth anomalies as early diagnosis of developmental disturbance in a single tooth may reveal a potential risk of future position or eruption disturbances of other teeth and thus allow early intervention (Bjerklin et al., 1992). Clinical Features In each of 4 Finnish kindreds, Svinhufvud et al. (1988) found a typical type of malposition of cuspids (canine teeth): palatal displacement of upper lateral incisor(s) and/or cuspid(s) in kindred A; labial displacement of upper cuspids, sometimes also lower cuspids, in kindred B; rotated upper cuspid(s) in kindred C; and labial cuspid(s), with rotated, malpositioned, or missing second bicuspids in kindred D. In each kindred other anomalies occurred, such as malposition, malformation, or hypodontia of upper lateral incisors, second bicuspids, and lower central incisors. Alexandrakis et al. (2000) described 2 patients with nasolacrimal duct obstruction (NLDO), presenting as epiphora, caused by ectopic eruption of teeth. Surgical removal of the ectopic teeth compressing the nasolacrimal duct resulted in resolution of the lacrimal drainage obstruction. The authors concluded that ectopic eruption of teeth should be added to the differential diagnosis of NLDO. Inheritance Bjerklin et al. (1992) evaluated and provided follow-up of 4 groups of children selected by a disturbance of tooth development. Ninety-two had ectopic eruption of maxillary first permanent molars; 93 had infraocclusion of primary molars; 91 had ectopic eruption of maxillary canines; and 97 aplasia of premolars. Among all children, 69 to 79% had only a single type of disturbance. There was an additional disturbance in 18 to 28% of children, and 2 additional disturbances in 2 to 3% of children. Chi-square contingency testing showed that infraocclusion of primary molars and aplasia of premolars exhibited a higher prevalence in both directions compared to the expected population prevalence. Ectopic eruption of maxillary canines showed a significantly higher prevalence than expected in all the other 3 groups. Finally, ectopic eruption of maxillary first permanent molars increased the likelihood of infraocclusion of primary molars. Bjerklin et al. (1992) concluded that there is a common, presumably hereditary, etiology for the 4 conditions. This would be consistent with different manifestations of a single syndrome with incomplete penetrance for each manifestation. Canine displacement can occur in either of 2 directions: palatal or facial. Palatal displacement more often results in maxillary canine impaction, which occurs in 1 to 3% of the population. Peck et al. (1994) provided a review of published papers that found that palatal canine displacement occurs with other dental anomalies, such as tooth agenesis or other ectopically positioned teeth, can occur bilaterally, and has been demonstrated in families. Differences in frequencies of the trait between population groups have also been observed, with relatively higher expression among Europeans. All of these findings suggested a genetic component to palatal canine displacement. Pirinen et al. (1996) found that 38 (36%) of 106 Finnish probands with palatal displacement of the canine also had congenital absence of permanent teeth, or hypodontia, which was 4.5 times the prevalence of hypodontia in the general population. Among these probands, family history allowed for the construction of 35 informative pedigrees. Autosomal dominant inheritance of missing teeth was noted in 13 of 35 pedigrees, and hypodontia was noted in about 20% of both first and second-degree relatives of probands with palatally impacted canines. Six of 35 pedigrees had a palatally impacted canine in several generations. The prevalence of this anomaly was 4.9% in the studied group, which was 2.5 times that of the general population. Pirinen et al. (1996) concluded that palatally displaced canine belongs to a spectrum of dental anomalies related to incisor-premolar hypodontia. In Malta, the prevalence of ectopic canines is 4 to 5.5%, possibly due to a founder effect. In a study of 63 affected Maltese probands and their families, Camilleri et al. (2008) found evidence for a single autosomal dominant gene with incomplete penetrance and variable expression. However, only 2 of 7 pairs of monozygotic twins were concordant for ectopic canines, suggesting that environmental or epigenetic factors may also be important. There was a female predominance (F:M of 1.89), which had been noted in earlier studies (Peck et al., 1994). INHERITANCE \- Autosomal dominant HEAD & NECK Teeth \- Ectopic teeth \- Malposition of teeth \- Hypodontia \- Palatal canine MISCELLANEOUS \- Incomplete penetrance \- Variable expressivity ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor

MALPOSITION OF TEETH WITH OR WITHOUT HYPODONTIA/OLIGODONTIA

c2752157

omim

https://www.omim.org/entry/189490

{"omim": ["189490"], "synonyms": ["Alternative titles", "ECTOPIC ERUPTION OF TEETH"]}

Perlman syndrome is a rare condition that affects the kidneys. People with this condition are generally born with renal abnormalities and have an increased risk for Wilms tumor, a rare kidney cancer that primarily affects children. Other signs and symptoms include a large birth size, low-muscle tone, characteristic facial features and developmental delay. Although the exact cause of Perlman syndrome is currently unknown, it appears to follow an autosomal recessive pattern of inheritance. Treatment is supportive and based on the signs and symptoms present in each person. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor

Perlman syndrome

c0796113

gard

https://rarediseases.info.nih.gov/diseases/3936/perlman-syndrome

{"mesh": ["C536399"], "omim": ["267000"], "umls": ["C0796113"], "orphanet": ["2849"], "synonyms": ["Nephroblastomatosis fetal ascites macrosomia and wilms tumor", "Renal hamartomas, nephroblastomatosis, and fetal gigantism"]}

## Summary ### Clinical characteristics. Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to older than 50 years; symptoms vary among and within families. * Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. * Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). * Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body. ### Diagnosis/testing. Wilson disease is suspected in a proband with varying combinations of hepatic, neurologic, and psychiatric findings. The diagnosis is established in most instances by a combination of biochemical findings (low serum copper and ceruloplasmin concentrations, and increased urinary copper excretion) and clinical findings (Kayser Fleischer corneal ring) or detection of biallelic ATP7B pathogenic variants on molecular genetic testing. Of note, when results from molecular genetic testing are not available to allow timely diagnosis, quantification of hepatic liver content (biopsy) may be required for diagnosis. In this instance, molecular genetic testing is strongly encouraged for confirmation of the diagnosis. ### Management. Treatment of manifestations: Treatment with copper chelating agents or zinc – initiated as soon as possible – can reduce hepatic, neurologic, and psychiatric findings in many symptomatic individuals. Treatment is life long. Copper chelating agents (D-penicillamine or trientine) increase urinary excretion of copper. High-dose oral zinc interferes with absorption of copper from the gastrointestinal tract and is most effective after initial decoppering with a chelating agent. Orthotopic liver transplantation is used for individuals who fail to respond to medical therapy or present with fulminant acute liver failure. Prevention of primary manifestations: Treatment with copper chelating agents or zinc can prevent the development of hepatic, neurologic, and psychiatric findings in asymptomatic affected individuals. Surveillance: At least twice annually: serum copper and ceruloplasmin, liver biochemistries, international normalized ratio, complete blood count, urinalysis, and physical examination including neurologic assessment. At least once annually: 24-hour urinary excretion of copper. Agents/circumstances to avoid: Foods very high in copper (liver, brain, chocolate, mushrooms, shellfish, and nuts), especially at the beginning of treatment. Evaluation of relatives at risk: If the pathogenic variants in an affected family member are known, molecular genetic testing of sibs of a proband allows early diagnosis and initiation of therapy before symptoms occur. If the pathogenic variants in an affected family member are not known, biochemical assessment of parameters of copper metabolism (serum copper, urinary copper, ceruloplasmin) and liver function tests as well as ultrasound imaging of the liver and slit lamp examination for the presence of Kayser-Fleischer rings can be conducted. Pregnancy management: Treatment must be continued during pregnancy because of the risk for fulminant hepatic failure or irreversible neurologic deterioration. Because of possible adverse effects on the fetus from chelating agents, the dose should be kept as low as possible. ### Genetic counseling. Wilson disease is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the ATP7B pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal testing and preimplantation genetic testing for pregnancies at increased risk for Wilson disease are possible. ## Diagnosis The diagnosis of Wilson disease cannot be made by a single test alone: a combination of tests is always required, as outlined in detail in the most current US guidelines, the American Association for the Study of Liver Diseases (AASLD) guidelines [Roberts & Schilsky 2008]. The diagnostic algorithm of the more recent European Association for Study of Liver (EASL) Clinical Practice Guidelines [European Association for Study of Liver 2012] is based on a diagnostic index ("Leipzig" score) proposed by an expert panel [Ferenci et al 2003]. This score includes clinical, biochemical, and molecular features, but has not been validated in large patient series. ### Suggestive Findings Wilson disease is suspected in individuals age three to 60 years (commonly 6-45 years) [Ferenci et al 2007] with varying combinations of hepatic, neurologic, psychiatric, and ocular findings. * Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. * Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). * Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. * Kayser-Fleisher rings, copper deposits in the periphery of the cornea, are observed in approximately 50%-60% of individuals with liver disease and about 90% of individuals with either neurologic findings or psychiatric disturbance. They are observed most reliably by slit lamp examination. ### Establishing the Diagnosis The diagnosis of Wilson disease is established in most instances by biochemical findings. If observed in combination with low ceruloplasmin levels, the presence of Kayser-Fleisher rings is almost pathognomonic. The diagnosis is confirmed by molecular genetic testing. Note: If timing during diagnostic testing is an issue and if the results from molecular genetic testing may not be available immediately, quantification of hepatic iron content (on biopsy) may be required. In this instance, molecular genetic testing is also strongly encouraged for confirmation (see Table 2 in Ferenci et al [2003]). #### Biochemical Findings The biochemical diagnosis of Wilson disease in a symptomatic individual relies on a combination of the following findings: * Low serum ceruloplasmin concentration * In children, interpretation of test results requires age correction or age-specific reference ranges. Note: Healthy newborns have low serum ceruloplasmin concentrations. The concentrations increase during the first six months of life and peak by age two to three years at a concentration that may exceed the healthy adult reference range. * In adults with Wilson disease, serum ceruloplasmin concentration is often below the normal range and typically very low. Note: A normal serum ceruloplasmin concentration is found in at least 5% of individuals with Wilson disease with neurologic symptoms and up to 40% of individuals with hepatic symptoms [Steindl et al 1997]. Serum ceruloplasmin concentration is, therefore, not a reliable screening test for Wilson disease. * Serum concentration of copper and of non-ceruloplasmin-bound copper * Most individuals with Wilson disease have a subnormal serum copper concentration that is proportional to the serum ceruloplasmin concentration. Note: Serum copper is low in healthy newborns. The concentrations increase during the first six months of life and by age two to three years peak at a concentration that may exceed the healthy adult reference range. * The combination of low ceruloplasmin serum concentration and a normal or high serum copper concentration may suggest excess non-ceruloplasmin-bound copper in the serum. Such high non-ceruloplasmin-bound serum copper concentrations often present as a result of copper overload; however, it is not reliable for diagnosis because of its high dependency on the accuracy of both the serum ceruloplasmin concentration and the serum copper concentration. The serum concentration of non-ceruloplasmin-bound copper (in µg/L) is most reliably estimated by subtracting the amount of copper associated with ceruloplasmin, determined by the enzymatic assay (ceruloplasmin in mg/L x 3.15) from the total serum copper concentration. Normal serum concentration of non-ceruloplasmin-bound copper is approximately 50-100 µ/L. In individuals with Wilson disease, the serum concentration of non-ceruloplasmin-bound copper is usually higher than 200 µ/L. Note: Enzymatic methods for quantification of ceruloplasmin measure holoceruloplasmin (i.e., with copper incorporated) and are therefore preferred, particularly for calculation of the free copper concentration [Walshe 2003b, Macintyre et al 2004]. * High urinary copper. Measurement of copper in three 24-hour urine collections, free from contamination by external sources of copper, is advised. The testing laboratory should be consulted regarding its trace-element urine collection protocol prior to initiating urine specimen collection. * Basal urinary copper excretion (without the use of chelating agent) is almost invariably elevated above 0.6 µmol/24 hours in the symptomatic individual. * A provocative test of urinary copper excretion following oral administration of D-penicillamine has been validated only in pediatric cohorts, but has proven useful in many cases [Martins da Costa et al 1992], although levels in affected individuals can overlap with those of heterozygotes. * Increased hepatic copper concentration. Hepatic copper concentration in Wilson disease is usually greater than 250 µg/g dry weight (normal: <55 µg/g dry weight [Nuttall et al 2003]); however, such levels may be seen in other chronic liver disorders and in cholestatic conditions as well. Note: (1) In later stages of Wilson disease, copper is distributed unevenly in the liver and measurement of hepatic copper concentration is less reliable. (2) Some individuals have only a moderately elevated hepatic copper concentration: 100 to 250 µg/g dry weight, which overlaps with values occasionally found in heterozygotes. Thus, hepatic copper concentration in this range does not exclude the diagnosis of Wilson disease. #### Molecular Genetic Testing The molecular diagnosis of Wilson disease relies on identification of biallelic pathogenic variants in ATP7B on molecular genetic testing (see Table 1). Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing. Single-gene testing. Sequence analysis of ATP7B is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. Targeted analysis for specific pathogenic variants can be performed first in individuals from specific populations: * Populations of European origin. p.His1069Gln accounts for 35%-45% of Wilson disease-causing alleles in a mixed European population [Tanzi et al 1993] and a greater percent in Eastern Europe [Caca et al 2001]. The frequency of this pathogenic variant may be somewhat lower in probands with childhood onset and in probands presenting with liver disease. * Asian populations. p.Arg778Leu is the only relatively common pathogenic variant, accounting for approximately 57% of Wilson disease-causing alleles in the Asian population younger than age 18 years [Thomas et al 1995]. * In Sardinia. A single pathogenic variant, a15-bp deletion in the 1-kb promoter region (c.-441_-427del15) is common [Loudianos et al 1999]. A multigene panel that includes ATP7B and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. More comprehensive genomic testing (when available) including exome sequencing, mitochondrial sequencing, and genome sequencing may be considered if single-gene testing (and/or use of a multigene panel that includes ATP7B) fails to confirm a diagnosis in an individual with features of Wilson disease. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Wilson Disease View in own window Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method ATP7BSequence analysis 398% 4 Gene-targeted deletion/duplication analysis 5Rare 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Stättermayer et al [2014] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. Large deletions and duplications, encompassing one or more exons, are rare. Exon and multiexon deletions have been reported (see, e.g., Møller et al [2005], Incollu et al [2011], Møller et al [2011], Tatsumi et al [2011]. ## Clinical Characteristics ### Clinical Description Wilson disease can manifest as hepatic, neurologic, hematologic, or psychiatric disturbances, or a combination of these, in individuals ranging in age from three years to older than 60 years. Phenotypic expression varies even within families. The phenotypic spectrum has further expanded through molecular genetic testing, which has confirmed the diagnosis in individuals with atypical clinical and biochemical findings [Cox & Roberts 2006, Ala et al 2007, Bandmann et al 2015]. Table 2 outlines the typical clinical findings of Wilson disease. Of note, the "classic triad" of liver disease, movement disorder, and Kayser-Fleischer ring is uncommon. ### Table 2. Clinical Findings in Individuals with Wilson Disease by Presenting Finding View in own window Presenting Finding% of IndividualsTypical Age of Presentation (Range)Liver DiseaseNeurologic DiseasePsychiatric DisturbanceKayser-Fleischer Rings Liver disease~40%6-45 (3-70)++/–+/–~50% Neurologic disease~40%Mid-teen to mid-adult (6-50)–/mild++/–~90% Psychiatric disturbance~20%Adolescent to young adult–/mild+/–+~90% Hemolytic anemiaFew %Adolescent to young adult+––+ Bruha et al [2011], Weiss et al [2011], Hofer et al [2012], Weiss et al [2013b] Liver disease. Wilson disease manifests as liver disease more commonly in children and younger adults, typically between ages six and 45 years; however, severe liver disease can be the initial finding in preschool-aged children [Wilson et al 2000] and in older adults. The clinical manifestations vary and can include the following findings: * Recurrent jaundice, possibly caused by hemolysis * Simple, acute, self-limited hepatitis-like illness with fatigue, anorexia, abdominal pain * Autoimmune hepatitis, often manifest acutely with fatigue, malaise, arthropathy, and rashes. This form of liver disease responds well to chelation therapy even if cirrhosis is present (see Management). * Fulminant hepatic failure with severe coagulopathy, encephalopathy, acute Coombs-negative intravascular hemolysis, and often rapidly progressive renal failure. Serum activity of aminotransferases is only moderately increased, and serum concentration of alkaline phosphatase is normal or extremely low. These individuals do not respond to chelation treatment and require urgent liver transplantation (see Management). * Chronic liver disease with portal hypertension, hepatosplenomegaly, ascites, low serum albumin concentration, and coagulopathy * Fatty liver of mild to moderate degree with abnormal liver function * Hemolytic anemia, with either acute or chronic hemolysis, a reflection of a high serum concentration of non-ceruloplasmin-bound copper, which leads to destruction of erythrocytes. Liver disease is likely to be present in such individuals, as are Kayser-Fleischer rings. Recurrent hemolysis predisposes to cholelithiasis, even in children. Neurologic disease. Neurologic involvement follows two general patterns: movement disorders or rigid dystonia. * Movement disorders tend to occur earlier and include tremors, poor coordination, loss of fine-motor control, micrographia (abnormally small, cramped handwriting), chorea, and/or choreoathetosis. * Spastic dystonia disorders manifest as mask-like facies, rigidity, and gait disturbance [Svetel et al 2001]. Pseudobulbar involvement such as dysarthria, drooling, and difficulty swallowing is more common in older individuals, but also occurs in children and adolescents. In contrast to the neurologic findings in individuals with a frank neurologic presentation, the neurologic findings in individuals with a hepatic presentation may be subtle. Mood disturbance (mainly depression; occasionally poor impulse control), changes in school performance, and/or difficulty with fine motor skills (especially handwriting) or gross motor skills may be observed. Psychiatric manifestations. The psychiatric manifestations are variable. Depression is common. Neurotic behavior includes phobias, compulsive behaviors, aggression, or antisocial behavior. Older individuals may have subtle psychopathology (e.g., progressive disorganization of personality with anxiety) and affective changes (e.g., labile mood and disinhibition). Intellectual deterioration may also occur with poor memory, difficulty in abstract thinking, and shortened attention span. Pure psychotic disorders are uncommon. Kayser-Fleischer rings result from copper deposition in Descemet's membrane of the cornea, and reflect a high degree of copper storage in the body. They do not affect vision and are reduced or disappear with effective decoppering treatment (see Management). Other findings * Renal involvement. Low-molecular weight proteinuria, microscopic hematuria, and Fanconi syndrome * Arthritis. Involvement of large joints from synovial copper accumulation * Reduced bone mineral density with a prevalence of osteoporosis in approximately 10% of affected individuals * Pancreatitis, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis of skeletal muscle, and various endocrine disorders * Sunflower cataracts observed occasionally on slit lamp examination Hepatocellular carcinoma rarely develops in Wilson disease: the estimated incidence is below 1% [Devarbhavi et al 2012]. However, abdominal malignancies have been reported in treated individuals [Walshe et al 2003]. Fertility and pregnancy. Most individuals with Wilson disease are fertile. Successful pregnancies of women with Wilson disease who received treatment have been reported [Brewer et al 2000, Tarnacka et al 2000, Furman et al 2001]. Prior to diagnosis and treatment, affected women may experience infertility or recurrent miscarriage. ### Genotype-Phenotype Correlations Pathogenic variants that abolish ATP7B function tend to result in a more severe phenotype than some missense variants [Cox 1996, Deguti et al 2004, Liu et al 2004, Panagiotakaki et al 2004]. Several studies have found a mean age of onset of 20 to 22 years in individuals homozygous for the common p.His1069Gln pathogenic variant [Stapelbroek et al 2004], although earlier onset also occurs. Marked differences between disease severity and clinical features in sibs suggest that the clinical outcome is influenced by modifying factors. It has been proposed that the clinical phenotype of Wilson disease is modified by pathogenic variants in other genes including MTHFR (encoding methylenetrahydrofolate reductase) [Gromadzka et al 2011], COMMD1 [Weiss et al 2006], ATOX1 [Simon et al 2008], and XIAP [Weiss et al 2010]. Although some minor associations have been reported, to date none of these genes is clinically relevant or has a significant diagnostic or predictive value. ### Nomenclature The neurologic form of Wilson disease has also been known as Westphal-Strumpell pseudosclerosis. ### Prevalence The prevalence of Wilson disease is estimated at one in 30,000 in most populations, with a corresponding carrier frequency in the general population of one in 90 [Bachmann et al 1991, Reilly et al 1993, Olivarez et al 2001]. Recent studies suggest a prevalence as high as one in 10,000 [Coffey et al 2013], especially in isolated populations such as Sardinia [Gialluisi et al 2013]. ## Differential Diagnosis Other liver diseases presenting with abnormal liver biochemistries with or without hepatomegaly that need to be considered include the following: * Chronic viral hepatitis * Autoimmune hepatitis * Non-alcoholic steatohepatitis (NASH) Note: Wilson disease must be specifically excluded in individuals thought to have NASH or the opportunity for life-saving treatment will be missed. * Primary sclerosing cholangitis (OMIM 613806) * Drug hepatotoxicity * HFE-associated hereditary hemochromatosis * Alpha-1-antitrypsin deficiency * Alcoholic liver disease * Primary biliary cirrhosis (OMIM 109720) Other liver diseases presenting as fulminant hepatic failure that need to be considered are acute viral hepatitis of any etiology and severe drug toxicity. Kayser-Fleischer rings are not specific for Wilson disease and may in extremely rare cases be seen in copper accumulation associated with cholestatic liver diseases or autoimmune hepatitis. Subnormal serum concentration of ceruloplasmin is not per se specific for Wilson disease, as ceruloplasmin synthesis can be reduced with acute liver failure or decompensated cirrhosis of any etiology. Decreased serum concentrations of ceruloplasmin are observed in protein-losing enteropathy, nephrotic syndrome, and malnutrition, but also in some heterozygotes for Wilson disease. Serum concentration of ceruloplasmin is physiologically low in neonates. Almost complete absence of ceruloplasmin is found in hereditary aceruloplasminemia, which results in iron storage [Miyajima et al 1987, Yoshida et al 1995]. Elevated liver copper content greater than 250 µg/g dry weight may be seen in other chronic liver disorders as well. As copper is secreted exclusively via the bile, hepatic copper concentration cannot be used as a diagnostic finding in persons with chronic cholestasis or impaired biliary excretion. Familial/environmental copper storage diseases not related to Wilson disease have been identified but are rare; the most common of these is Indian childhood cirrhosis. Other neurologic disorders that need to be considered: * Benign familial or essential tremors * Parkinson disease and its differential diagnoses, including: * Huntington disease * Dentatorubro-pallidoluysian atrophy (DRPLA) * Juvenile Parkinson disease, including Parkin type of early onset parkinsonism * Inherited forms of dystonia (see Dystonia Overview), including: * DYT1 early-onset primary dystonia * Dopa-responsive dystonia (DRD) * Neurodegenerative diseases * Drug effects or toxicity * Hyperthyroidism * Central nervous system neoplasia * Hereditary ataxias * Niemann-Pick disease type C (associated with liver disease) ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Wilson disease, the following evaluations are recommended: * Evaluation of severity of the liver disease by liver biopsy or by biochemical testing and imaging of the liver * Upper GI endoscopy to exclude or confirm esophageal varices * Detailed clinical neurologic assessment. A validated neurologic rating scale is available [Członkowska et al 2007]. * Brain MRI to assess for structural alteration * Assessment of kidney function * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations The goal of therapy is to institute treatment with chelating agents as soon as possible in individuals with symptomatic Wilson disease. See extensive review by the American Association for the Study of Liver Diseases [Roberts & Schilsky 2008] (full text) and EASL Clinical Practice Guidelines: Wilson's disease [European Association for Study of Liver 2012] (full text). * Treatment is life long, including during pregnancy. * If one treatment modality is discontinued, an alternative modality must be substituted. * Discontinuation of all treatment leads to hepatic and neurologic decompensation, which is usually refractory to further medical intervention. Copper chelating agents that increase urinary excretion of copper are the first-line treatment for persons with symptomatic Wilson disease. Note: Routine institution of chelation therapy before age three years has not been adequately assessed and may have adverse effects on growth. * D-penicillamine (chelator). Used since the 1950s as first-line therapy for Wilson disease [Durand et al 2001, Walshe 2003a], D-penicillamine is given as tablets by mouth two or three times daily. Pyridoxine must be given along with D-penicillamine. Twenty-four-hour urine copper excretion is used to confirm chelation and increased excretion of copper. Urinary copper values should be five to ten times normal; if the values are lower, non-compliance may be an issue, or body copper stores may have been adequately depleted. * Complete blood count and urinalysis must be monitored regularly during D-penicillamine therapy. Serious side effects can occur in up to 30% of individuals, and include: severe thrombocytopenia, leukopenia, aplastic anemia, proteinuria, nephrotic syndrome, polyserositis, Goodpasture syndrome, and severe skin reactions. An early allergic reaction with fever, rash, and proteinuria may occur. Evidence of any such side effects may require discontinuation of D-penicillamine and substitution of an alternate treatment. If such alternate therapies are unavailable, D-penicillamine-induced adverse events may be manageable by co-administration of steroids. * D-penicillamine inhibits collagen cross-linking and has some immunosuppressant properties. After decades of treatment, individuals may have abnormal skin and connective tissue collagen, and possible chronic depletion of copper and (possibly) other trace metals. * D-penicillamine should NOT be used simultaneously with zinc, pending adequate clinical assessment of this treatment strategy. * Trientine (chelator), also known as triethylene tetramine dihydrochloride (2,2,2-tetramine) or trien, is the usual second-line treatment for individuals who cannot tolerate D-penicillamine. It is gaining acceptance as a first-line drug because of good efficiency and better tolerance than D-penicillamine; however, it is still not generally available in all countries. * Complete blood count and urinalysis must be monitored regularly in all individuals on trientine. * Rare side effects include gastritis with nausea and, in cases of overtreatment, iron deficiency anemia. * Trientine should NOT be used simultaneously with zinc pending adequate assessment of this combination. Current reports suggest that the combination of trientine and zinc, temporally dispersed throughout the day such that each drug is administered 5-6 hours apart from the other, may be effective in severely decompensated hepatic Wilson disease [Santos Silva et al 1996, Askari et al 2003]. Zinc (metallothionein inducer). High-dose oral zinc interferes with absorption of copper from the gastrointestinal tract presumably by inducing enterocyte metallothionein, which preferentially binds copper from the intestinal contents and is lost in the feces as enterocytes are shed in normal turnover. Zinc therapy is most effective after initial decoppering with a chelating agent [Brewer 2001, Brewer et al 2001]. In selected cases, it can be used as an initial treatment [Milanino et al 1992, Linn et al 2009]. Zinc is taken as tablets by mouth at least twice (usually 3x) daily, before meals. The dose is based on the elemental zinc in the tablet. Twenty-four-hour urine copper excretion is used to monitor total body copper stores, which should decrease. Increase of urinary copper excretion under zinc therapy may indicate insufficient treatment efficacy [Weiss et al 2011]. The computed estimate of non-ceruloplasmin-bound copper may be used to titrate the zinc dose. Serum or urinary zinc concentration can be measured to monitor compliance in individuals taking zinc. Note: (1) Gastritis, a common side effect, can be reduced with the use of zinc acetate or zinc gluconate; (2) zinc should NOT be used simultaneously with any chelator, pending further clinical investigation. Antioxidants. Serum and hepatic vitamin E concentrations are reported to be low in individuals with Wilson disease [Sokol et al 1994, Ogihara et al 1995], likely because of excessive consumption to counteract free radicals produced by excess copper. Antioxidants such as vitamin E may be used along with a chelator or zinc in protecting tissues from damage. Restriction of foods very high in copper (liver, brain, chocolate, mushrooms, shellfish, and nuts) is likely prudent, especially at the beginning of treatment. It is recommended that individuals with special dietary needs (e.g., vegetarians) consult with a trained dietitian. Orthotopic liver transplantation (OLT) is reserved for individuals who fail to respond to medical therapy or cannot tolerate it because of serious adverse side effects [Schilsky et al 1994, Emre et al 2001, Sutcliffe et al 2003]. It remains controversial whether orthotopic liver transplantation should be a primary treatment for individuals with Wilson disease who have severe neurologic disease [Medici et al 2005, Weiss et al 2013a]. ### Prevention of Primary Manifestations Medical therapy is recommended for asymptomatic patients to prevent development of symptoms (see Treatment of Manifestations). ### Prevention of Secondary Complications Monitoring of patients under therapy should include routine assessments of treatment efficacy by biochemical testing and clinical evaluation: * Insufficient therapy, underdosage, or malcompliance could lead to reaccumulation of copper and development of new symptoms. * Adverse events related to medical treatment (especially under D-penicillamine treatment) should be evaluated. * Excessive long-term treatment could result in copper deficiency, leading to immobilization of iron (as observed in aceruloplasminemia) and to neurologic symptoms of copper deficiency [Horvath et al 2010, da Silva-Júnior et al 2011]. ### Surveillance According to current guidelines (AASLD [Roberts & Schilsky 2008] and EASL Clinical Practice Guidelines [European Association for Study of Liver 2012]), routine monitoring should include the following examinations: * At least twice annually: serum copper and ceruloplasmin, liver biochemistries, international normalized ratio, complete blood count, urinalysis, and physical examination including neurologic assessment Note: Patients receiving chelation therapy require a complete blood count and urinalysis regularly, no matter how long they have been on treatment * At least once annually: 24-hour urinary excretion of copper Note: Measurements are recommended more frequently if there are questions on compliance or if dosage of medications is adjusted. ### Agents/Circumstances to Avoid Foods very high in copper (liver, brain, chocolate, mushrooms, shellfish, and nuts) should be avoided, especially at the beginning of treatment. ### Evaluation of Relatives at Risk The goal is to identify those sibs of a proband who have Wilson disease preferably before symptoms occur so that the therapies described under Treatment of Manifestations can be initiated as soon as possible. Evaluations can include the following: * Molecular genetic testing if both ATP7B pathogenic variants in the proband are known * If the pathogenic variants in an affected family member are not known, biochemical assessment of parameters of copper metabolism (serum copper, urinary copper, ceruloplasmin) and liver function tests as well as ultrasound imaging of the liver and slit lamp examination for the presence of Kayser-Fleischer rings Note: Because presymptomatic individuals generally have a low serum concentration of ceruloplasmin and mildly increased basal 24-hour urinary copper excretion, biochemical testing can be used; however, sometimes asymptomatic affected individuals cannot be distinguished from heterozygotes. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Treatment must be continued during pregnancy because of the risk of fulminant hepatic failure. * D-penicillamine has been used in many pregnancies with no adverse outcomes; however, congenital connective tissue disorders encompassing inguinal hernias and skin laxity have been reported in some exposed infants. Such adverse outcomes may depend on dose, which should be kept as low as possible. The dose of D-penicillamine should be maintained at the lowest effective dose with the plan to reduce by approximately 30% in the third trimester if the mother has been well chelated prior to pregnancy. A possible over-chelated (copper deficiency) status prior to pregnancy or genetic characteristics of the mother can contribute to fetal abnormalities [Pinter et al 2004]. * Trientine has been used successfully during pregnancy, but the total number of reported cases is small. Reduction of the dose to the lowest effective dose is recommended using a comparable approach to that for D-penicillamine. * Zinc has been used effectively during pregnancy. See MotherToBaby for further information on medication use during pregnancy. ### Therapies Under Investigation Ammonium tetrathiomolybdate (chelator) interferes with copper absorption from the intestine and binds plasma copper with high affinity. It may be useful for treatment of severe neurologic Wilson disease because, unlike D-penicillamine, it appears not to be associated with early neurologic deterioration [Brewer et al 2003]. However, the ammonium salt has not proven suitable for oral formulations. Choline tetrathiomolybdate (chelator) is a more stable salt formulation of tetrathiomolybdate and is currently under investigation for Wilson disease [Weiss et al 2015]. Curcumin. Experimental in vitro studies suggest partially restored protein expression of some ATP7B mutants by curcumin [van den Berghe et al 2009]. This could enable novel treatment strategies in Wilson disease by directly enhancing the protein expression of mutated ATP7B with residual copper export activity. Furthermore, curcumin is an ideal antioxidant and an effective scavenger of reactive oxygen species and can act as a copper chelating agent. However, clinical data in patients with Wilson disease are not yet available. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor

Wilson Disease

c0019202

gene_reviews

https://www.ncbi.nlm.nih.gov/books/NBK1512/

{"mesh": ["D006527"], "synonyms": ["Hepatolenticular Degeneration"]}

Familial male limited precocious puberty (FMPP) is a gonadotropin-independent familial form of male-limited precocious puberty, generally presenting between 2-5 years of age as accelerated growth, early development of secondary sexual characteristics and reduced adult height. ## Epidemiology FMPP is a very rare condition; prevalence is less than 1/1,000,000. ## Clinical description FMPP presents in boys from 2-5 years of age with precocious signs of puberty including growth acceleration, penile enlargement, acne, pubic hair and facial hair. Spontaneous erection and masturbatory behavior are commonly observed. Testicular volume is moderately increased, in contrast to central precocious puberty (see this term) where testicular volume is markedly enlarged, similar to normal puberty. Presentation is variable, even between siblings, but most untreated patients have been reported to have premature epiphyseal fusion resulting in a compromised adult height. Aggressive behavior and social exclusion may occur. Mild oligospermia has been reported in some adults, but most individuals retain fertility. An increased risk of attention-deficit hyperactivity disorder (ADHD) has been observed. ## Etiology FMPP is caused by an activating mutation of the Lutropin-Choriogonadotropic Hormone Receptor gene (LHCGR, 2p21) which leads to increased levels of sex steroids in the context of low luteinizing hormone. This receptor's chronic activation leads to precocious testosterone production by Leydig cells. No effect is observed in female carriers due to the dual luteinizing hormone (LH)/ follicle stimulating hormone (FSH) signal necessary to promote ovarian stimulation. ## Diagnostic methods Patients display increased serum testosterone levels (typically 3- 20 nmol/l) and decreased secretion of gonadotropins, even after stimulation with luteinizing hormone-releasing hormone (LHRH). Radiological examination reveals skeletal maturation. Diagnosis is confirmed by genetic testing identifying activating mutations in the LHCGR gene. ## Differential diagnosis Differential diagnoses include other causes of precocious puberty associated with low levels of gonadotropins such as adrenal tumors, testicular Leydig cell tumors (ruled out by testicular ultrasound since they can be of small size), human chorionic gonadotropin (HCG)-secreting tumors, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, CAH due to 11-beta-hydroxylase deficiency, central precocious puberty (with detectable LH levels that can be stimulated by gonadotropin-releasing hormone (GnRH) or GnRH agonists) (see these terms), and occult exposure to androgens. ## Antenatal diagnosis Prenatal genetic screening is feasible when a proband has been identified. ## Genetic counseling Transmission is autosomal dominant. Mothers may act as silent carriers, with each son having a 50% risk of displaying FMPP. ## Management and treatment Treatment consists in reducing hyperandrogenism in children (sexual maturation, stature). Two options have been proposed. The first one consists of administrating the androgen antagonist bicalutamide (12.5-100 mg/d) together with aromatase inhibitors such as anastrozole (1 mg/d) or letrozole (2.5 mg/d) to normalize the growth rates until adult height has been reached. The second option consists of administrating androgen biosynthesis inhibitors such as ketoconazole (15 mg/kg/d) that result in a decrease in testosterone levels. In both cases, the treatments may be supplemented by GnRH therapy if central (gonadotropin-dependent) precocious puberty develops. Psychological counseling is needed to help the patient and family adjust to the stimulative effects of high androgen levels. ## Prognosis Prognosis is good; with treatment most patients reach an appropriate adult height. The disease does not seem to have any consequence during adulthood but this is based on limited clinical reports. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor

Familial male-limited precocious puberty

c0342549

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3000

{"gard": ["4475"], "mesh": ["C536961"], "omim": ["176410"], "umls": ["C0342549", "C1504412"], "icd-10": ["E30.1"], "synonyms": ["FMPP", "Familial gonadotropin-independent male-limited sexual precocity", "Male-limited precocious puberty", "Testotoxicosis"]}

This article needs editing for compliance with Wikipedia's Manual of Style. In particular, it has problems with not using MEDMOS. Please help improve it if you can. (July 2017) (Learn how and when to remove this template message) Estrogen insensitivity syndrome Other namesEIS; Complete estrogen insensitivity syndrome; CEIS[1] EIS results when the function of the estrogen receptor alpha (ERα) is impaired. The ERα protein (pictured) mediates most of the effects of estrogens in the human body. SpecialtyEndocrinology Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen deficiency or hypoestrogenism[2] which is caused by a defective estrogen receptor (ER) – specifically, the estrogen receptor alpha (ERα) – that results in an inability of estrogen to mediate its biological effects in the body.[3] Congenital estrogen deficiency can alternatively be caused by a defect in aromatase, the enzyme responsible for the biosynthesis of estrogens, a condition which is referred to as aromatase deficiency and is similar in symptomatology to EIS.[4] EIS is an extremely rare occurrence.[5][6] As of 2016, there have been three published reports of EIS, involving a total of five individuals.[6] The reports include a male case published in 1994,[7][8] a female case published in 2013,[5][9] and a familial case involving two sisters and a brother which was published in 2016.[6] EIS is analogous to androgen insensitivity syndrome (AIS), a condition in which the androgen receptor (AR) is defective and insensitive to androgens, such as testosterone and dihydrotestosterone (DHT). The functional opposite of EIS is hyperestrogenism, for instance that seen in aromatase excess syndrome. ## Contents * 1 History * 1.1 Male case * 1.2 Female case * 1.3 Familial case * 2 Research * 2.1 αERKO mice * 2.1.1 Females * 2.1.2 Males * 2.2 βERKO mice * 2.2.1 Females * 2.2.2 Males * 2.3 GPERKO mice * 3 Androgen insensitivity syndrome * 4 References * 5 Further reading * 6 External links ## History[edit] ### Male case[edit] In 1994, a 28-year-old man with EIS was reported.[7][8] He was fully masculinized.[10] At 204 cm, he had tall stature.[7] His epiphyses were unfused, and there was evidence of still-occurring slow linear growth (for comparison, his height at 16 years of age was 178 cm).[7] He also had markedly delayed skeletal maturation (bone age 15 years), a severely undermineralized skeleton, evidence of increased bone resorption, and very early-onset osteoporosis.[7] The genitalia, testes, and prostate of the patient were all normal and of normal size/volume.[7] The sperm count of the patient was normal (25 million/mL; normal, >20 million/mL), but his sperm viability was low (18%; normal, >50%), indicating some degree of infertility.[7] The patient also had early-onset temporal hair loss.[7] He reported no history of gender identity disorder, considered himself to have strong heterosexual interests, and had normal sexual function, including morning erections and nocturnal emissions.[7] Follicle-stimulating hormone and luteinizing hormone levels were considerably elevated (30–33 mIU/mL and 34–37 mIU/mL, respectively) and estradiol and estrone levels were markedly elevated (145 pg/mL and 119–272 pg/mL, respectively), while testosterone levels were normal (445 ng/dL).[7] Sex hormone-binding globulin levels were mildly elevated (6.0–10.0 nmol/L), while thyroxine-binding globulin, corticosteroid-binding globulin, and prolactin levels were all normal.[7] Osteocalcin and bone-specific alkaline phosphatase levels were both substantially elevated (18.7–21.6 ng/mL and 33.3–35.9 ng/mL, respectively).[7] Treatment with up to very high doses of estradiol (fourteen 100-μg Estraderm patches per week) had no effect on any of his symptoms of hypoestrogenism, did not produce any estrogenic effects such as gynecomastia, and had no effect on any of his physiological parameters (e.g., hormone levels or bone parameters), suggesting a profile of complete estrogen insensitivity syndrome.[7] ### Female case[edit] In 2013, an 18-year-old woman with EIS was reported.[5][9] DNA sequencing revealed a homozygous mutation in ESR1, the gene that encodes the ERα.[9] Within the ligand-binding domain, the neutral polar glutamine 375 was changed to a basic, polar histidine.[9] An in vitro assay of ERα-dependent gene transcription found that the EC50 for transactivation had been reduced by 240-fold relative to normal, non-mutated ERα, indicating an extreme reduction in the activity of the receptor.[9] Clinical signs suggested a profile of complete estrogen insensitivity syndrome with a resemblance to ERα knockout mice.[9] The patient presented with delayed puberty, including an absence of breast development (Tanner stage I) and primary amenorrhea, as well as intermittent pelvic pain.[9] Examination revealed markedly enlarged ovaries with multiple hemorrhagic cysts as the cause of the lower abdominal pain.[9] Estrogen levels were dramatically and persistently elevated (estradiol levels were 2,340 pg/mL, regarded as being about 10 times the normal level, and ranged from 750–3,500 pg/mL), gonadotropin levels were mildly elevated (follicle-stimulating hormone and luteinizing hormone levels were 6.7–19.1 mIU/mL and 5.8–13.2 mIU/mL, respectively), and testosterone levels were slightly elevated (33–88 ng/dL).[9] Inhibin A levels were also markedly elevated.[9] Sex hormone-binding globulin, corticosteroid-binding globulin, thyroxine-binding globulin, prolactin, and triglycerides, which are known to be elevated by estrogen, were all within normal ranges in spite of the extremely high levels of estrogen, and inhibin B levels were also normal.[9] Her relatively mildly elevated levels of gonadotropins were attributed to retained negative feedback by progesterone as well as by her elevated levels of testosterone and inhibin A, although it was acknowledged that possible effects of estrogen mediated by other receptors such as ERβ could not be excluded.[9] The patient had a small uterus, with an endometrial stripe that could not be clearly identified.[9] At the age of 15 years, 5 months, her bone age was 11 or 12 years, and at the age of 17 years, 8 months, her bone age was 13.5 years.[9] Her bone mass was lower than expected for her age, and levels of osteocalcin and C-terminal telopeptide were both elevated, suggesting an increased rate of bone turnover.[9] She was 162.6 cm tall, and her growth velocity indicated a lack of estrogen-induced growth spurt at puberty.[9] The patient had normal pubic hair development (Tanner stage IV) and severe facial acne, which could both be attributed to testosterone.[9] Her ovarian pathology was attributed to the elevated levels of gonadotropins.[9] In addition to her absence of breast development and areolar enlargement, the patient also appeared to show minimal widening of the hips and a lack of subcutaneous fat deposition, which is in accordance with the established role of estrogen and ERα in the development of female secondary sexual characteristics.[9][11] Treatment of the patient with conjugated estrogens and high doses of estradiol had no effect.[9] Although the authors of the paper considered her ERα to be essentially unresponsive to estrogen, they stated that they "[could not] exclude the possibility that some residual estrogen sensitivity could be present in some tissues", which is in accordance with the fact that the EC50 of her ERα had been reduced 240-fold but had not been abolished.[9] Treatment with a progestin, norethisterone, reduced her estradiol concentrations to normal levels and decreased the size of her ovaries and the number of ovarian cysts, alleviating her hypothalamic-pituitary-gonadal axis hyperactivity and ovarian pathology.[9] ### Familial case[edit] In 2016, a familial instance of EIS involving three siblings was reported.[6] The afflicted individuals were a 25-year-old female, a 21-year-old female, and an 18-year-old male.[6] The family was consanguineous, with the parents of the siblings being first cousins.[6] The parents were both heterozygous for the causative mutation and were healthy and normal, while the three affected siblings were homozygous for the mutation, and a fourth sibling, an unaffected sister, was heterozygous.[6] The fact that the heterozygous parents and heterozygous sister were unaffected indicates that the disorder is transmitted in an autosomal recessive manner and that a single normal allele is sufficient to achieve normal puberty and fertility, which is consistent with what has been observed in ERα knockout mice.[6] All three siblings presented with pubertal failure.[6] Both of the sisters had no breast development (i.e., Tanner stage I), illustrating how the ERα is absolutely required for normal mammary gland development.[6] The older sister was overweight (BMI 26.3) and had mild incidental adipomastia,[6] or adipose tissue deposition in the breasts without true glandular tissue, a trait that is not indicative of pubertal development.[12][13] The sisters had complete pubic hair maturation (i.e., Tanner stage V), while the brother had Tanner stage II pubic hair development and Tanner stage I gonadal maturation.[6] The right testis of the brother was cryptorchid, while the left testis was severely hypoplastic, with a volume of less than 1 mL.[6] Both of the sisters presented with primary amenorrhea and enlarged, multicystic ovaries, and the older sister had a small uterus and a thin endometrium.[6] The older sister had chest acne, which could be attributed to hyperandrogenism (see below).[6] All three siblings showed markedly delayed bone maturation for their chronological ages.[6] Surprisingly, the older sister was of normal height, while the younger sister was tall.[6] In all three siblings, estradiol levels were markedly elevated and gonadotropin levels were elevated.[6] In the sisters, estradiol levels were extremely high, more than 50-fold greater than normal levels, while gonadotropin levels were elevated 3-fold above the normal range.[6] Levels of progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, and dihydrotestosterone (DHT) were elevated in the sisters, while concentrations of adrenal steroids including cortisol, dehydroepiandrosterone (DHEA), 11β-hydroxyandrostenedione, 11-deoxycortisol, and 21-deoxycortisol were within normal ranges.[6] Levels of sex hormone-binding globulin (SHBG) were very low, which can be attributed to the absence of hepatic actions of estrogen.[6] In the older sister, anti-Müllerian hormone (AMH) levels were normal, while levels of inhibin A and inhibin B were significantly increased.[6] In the brother, levels of AMH and inhibin B were low, in conjunction with the patient's low concentrations of testosterone.[6] The low testosterone levels of the brother were probably related to his cryptorchidism, this symptom having not been previously reported in the earlier male case report of EIS.[6] Consistent with the brother's phenotype, cryptorchidism has been described in ERα knockout mice.[6] Because of the brother's low inhibin B levels, it was stated by the researchers that it was very likely that spermatogenesis would not occur in him.[6] Impaired negative feedback by estrogen on the hypothalamic-pituitary-gonadal (HPG) axis would account for the elevated estradiol and gonadotropin levels in the siblings and for the ovarian enlargement and cyst formation in the sisters.[6] All three siblings were homozygous for a missense mutation in the fifth coding exon of the ESR1 gene.[6] The mutation caused a change from guanine to adenine at complementary DNA nucleotide 1181 (c.1181G>A) in the gene, which resulted in the substitution of a histidine for an arginine at residue 394 (p.Arg394His) in the helix H5 of the ligand-binding domain (LBD) of the ERα protein.[6] This is a critical residue that is completely conserved among species and in the androgen receptor (AR) and mineralocorticoid receptor (MR).[6] Mutations involving the corresponding residue in the AR and MR have previously been associated with androgen insensitivity syndrome (AIS) and diminished sensitivity to mineralocorticoids, respectively.[6] Assays revealed that the mutated ERα showed strongly reduced transcriptional activity in response to stimulation by estradiol, with an ED50 that was approximately 65-fold greater than that of normal/wild-type ERα.[6] In the normal ERα, estradiol is anchored in the binding pocket of the receptor by three hydrogen bonds; the C3 and C17 hydroxyl groups of estradiol are anchored by the Glu353 and Arg394, and His524 residues of the ERα protein, respectively.[6] In the mutated ERα, the His394 residue is unable to properly anchor estradiol, which results in the dramatically reduced sensitivity and response of the receptor to estradiol relative to the normal ERα.[6] A group of other ERα agonists that included ethinylestradiol, diethylstilbestrol, tamoxifen, clomifene, and raloxifene were tested in their ability to promote transcriptional activity of the mutated ERα, but none of them were found to be more efficacious than estradiol in activating the mutated receptor and hence in overcoming the estrogen insensitivity of the siblings.[6] As the sisters had very high, supraphysiological levels of circulating estradiol, the authors cautioned that it could not be ruled out that estradiol may have exerted some functional influence on their phenotypes via signaling through the ERβ and GPER (i.e., that not all of the observed phenotypes may have simply been due to loss of ERα signaling).[6] Moreover, the authors noted that this might partially explain the variability in the phenotypes.[6] ## Research[edit] EIS can be experimentally induced in animals via knockout of the ER.[14] In these so-called ERKO mice, different ERs can be disabled allowing to study the role of these receptors.[14] ERKO mice show development of the respective female or male reproductive systems, and male and female αERKO mice are infertile, βERKO males are fertile while females are subfertile, male and female double αERKO and βERKO mice are infertile.[14] The uterus and mammary glands are hypoplastic and do not respond to exogenous stimulation by estrogens.[14] Males are infertile with atrophy in the testes.[14] Bone age is delayed and bones are more brittle.[citation needed] Variations in these patterns can be achieved by selectively disabling the ERα or ERβ.[14] The following sections are an extensive though partial/incomplete list of deficits observed in ERKO mice.[14] ### αERKO mice[edit] #### Females[edit] * Estradiol and LH levels are dramatically elevated due to loss of negative feedback by estradiol on the HPG axis.[14] FSH levels, in contrast, are normal.[14] Testosterone levels are also substantially elevated.[14] Prolactin levels are decreased by 5-fold, which is due to a loss of its estradiol-induced secretion from the anterior pituitary.[14] * The uterus and endometrium show hypoplasia and hypotrophy, respectively, and the vagina is atrophic.[14] The oviduct is normal.[14] The ovary is normal until sexual maturity, at which point there is complete anovulation and the ovaries become enlarged, hemorrhagic, and cystic.[14] Because there is complete anovulation, female αERKO mice are infertile.[14] The ovarian phenotype closely resembles that of polycystic ovary syndrome (PCOS) in humans.[14] It is caused by chronic exposure to abnormally high levels of LH.[14] By 18 months of age, there is a 30 to 40% incidence of ovarian tumors.[14] * The mammary gland is normal until puberty, at which point there is a complete absence of pubertal development and the gland remains in a prepubertal state.[14] * Body weight and body fat are increased.[14] There are signs of insulin resistance, as in PCOS in humans.[14] * Due to the substantially elevated testosterone levels, there is hyperandrogenism, including masculinization of the preputial glands.[14] In addition, female αERKO mice exhibit behavior that is similar to that of males in terms of parental, aggressive, and sexual activities.[14] There is a complete lack of sexual receptivity, measured as lordosis behavior.[14] There are significant deficits in parental behavior, including a tendency toward infanticide, and aggressive behavior is increased.[14] #### Males[edit] * LH and testosterone levels are both increased 2-fold due to loss of negative feedback by estradiol on the HPG axis.[14] * The testes develop relatively normally initially, but are slightly smaller than normal and possess various defects.[14] By 20 weeks, the weights of the testes, epididymis, and vas deferens are significantly decreased relative to those of normal mice.[14] However, there is a severe testicular phenotype with age, such that the testes are completely atrophied by 150 days of age.[14] Also, the testes show Leydig cell hyperplasia, which is due to the increased levels of LH and intratesticular testosterone.[14] Further, there is a greater incidence of cryptorchidism (undescended/retracted testes).[14] * There is complete infertility, which is due both to testicular defects and to severely compromised normal sexual behavior (see below).[14] Males can produce viable sperm, but there are severe deficits in both spermatogenesis and sperm function, the latter rendering produced sperm ineffective.[14] Sperm counts are significantly reduced, at 55% of those of normal mice, and further diminish with age, at 13% of those of normal mice by 16 weeks of age.[14] There are deficits in sperm motility, an increased incidence of sperm defects (specifically, sperm heads separated from the flagellum (tail)), and a complete inability of sperm to fertilize oocytes (assessed in vitro).[14] * There are no obvious abnormalities in the male accessory glands, including the prostate gland, bulbourethral glands, coagulating gland, and seminal vesicles.[14] However, there is a significant increase in weight of the seminal vesicles/coagulating gland that becomes more apparent with age, which is likely due to elevated testosterone levels.[14] * Aggressive behavior is dramatically reduced, whereas parental behavior, in terms of infanticide, is relatively normal.[14] There is little effect on sexual behavior in terms of mounting and sexual attraction to females.[14] However, there is an almost complete lack of intromission and ejaculation, in spite of the relatively normal mounting rate.[14] This contributes to infertility.[14] ### βERKO mice[edit] #### Females[edit] * The uterus, vagina, and oviducts are normal.[14] The ovary is normal prior to puberty, and there is still no gross aberrant phenotype during adulthood.[14] However, there is partial anovulation and subfertility, which is due to ovarian defects, namely compromised follicular maturation via loss of estradiol signaling in ovarian granulosa cells.[14] * The mammary gland appears to be normal.[14] * Body weight and fat distribution appear to be normal.[14] * Increased anxiety-like behavior is seen.[15] In addition, the antidepressant-like effects of exogenous estradiol in the forced swim test are lost.[15] #### Males[edit] * Fertility is full and normal, with a lack of relevant phenotypes observed.[14] * The male accessory glands, including the prostate gland, bulbourethral glands, coagulating gland, and seminal vesicles, all seem to be normal.[14] However, there is an increased incidence of prostate hyperplasia with age.[16] * Body weight and fat distribution appear to be normal.[14] * There is a lack of grossly apparent behavioral phenotypes, including in regards to sexual behavior.[14] However, increased aggressive behavior is observed.[15] ### GPERKO mice[edit] GPER knockout mice have also been generated, and exhibit obesity, cardiovascular dysfunction, insulin resistance, glucose intolerance, differences in mammary carcinogenesis and metastasis, and differences in central nervous system function.[17][18] ## Androgen insensitivity syndrome[edit] Main article: Androgen insensitivity syndrome In contrast to EIS, androgen insensitivity syndrome (AIS), a condition in which the androgen receptor (AR) is defective, is relatively common. This can be explained by the genetics of each syndrome. AIS is an X-linked recessive condition and thus carried over, by females, into future generations (although the most severe form, complete androgen insensitivity syndrome (CAIS), results in sterility, and hence cannot be passed on to offspring). EIS is not compatible with reproduction, thus each occurrence in humans would have to be a de novo mutation and is not transmitted to offspring.[citation needed] ## References[edit] 1. ^ Layman LC (2013). "The genetic basis of female reproductive disorders: etiology and clinical testing". Mol. Cell. Endocrinol. 370 (1–2): 138–48. doi:10.1016/j.mce.2013.02.016. PMC 3767392. PMID 23499866. 2. ^ Rochira V, Balestrieri A, Madeo B, Baraldi E, Faustini-Fustini M, Granata AR, Carani C, et al. (June 2001). "Congenital estrogen deficiency: in search of the estrogen role in human male reproduction". Molecular and Cellular Endocrinology. 178 (1–2): 107–15. doi:10.1016/S0303-7207(01)00432-4. PMID 11403900. 3. ^ Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS (1994). "Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man". N. Engl. J. Med. 331 (16): 1056–61. doi:10.1056/NEJM199410203311604. PMID 8090165. 4. ^ Rochira V, Balestrieri A, Madeo B, Spaggiari A, Carani C (July 2002). "Congenital estrogen deficiency in men: a new syndrome with different phenotypes; clinical and therapeutic implications in men". Molecular and Cellular Endocrinology. 193 (1–2): 19–28. doi:10.1016/S0303-7207(02)00092-8. PMID 12160998. 5. ^ a b c J. Larry Jameson; Leslie J. De Groot (25 February 2015). Endocrinology: Adult and Pediatric. Elsevier Health Sciences. pp. 238–. ISBN 978-0-323-32195-2. 6. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak Bernard V, Kherra S, Francou B, Fagart J, Viengchareun S, Guéchot J, Ladjouze A, Guiochon-Mantel A, Korach KS, Binart N, Lombès M, Christin-Maitre S (2017). "Familial Multiplicity of Estrogen Insensitivity Associated With a Loss-of-Function ESR1 Mutation". J. Clin. Endocrinol. Metab. 102 (1): 93–99. doi:10.1210/jc.2016-2749. PMC 5413105. PMID 27754803. 7. ^ a b c d e f g h i j k l m Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS (October 1994). "Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man". The New England Journal of Medicine. 331 (16): 1056–61. doi:10.1056/NEJM199410203311604. PMID 8090165. 8. ^ a b Korach KS, Couse JF, Curtis SW, Washburn TF, Lindzey J, Kimbro KS, Eddy EM, Migliaccio S, Snedeker SM, Lubahn DB, Schomberg DW, Smith EP (1996). "Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes". Recent Progress in Hormone Research. 51: 159–86, discussion 186–8. PMID 8701078. 9. ^ a b c d e f g h i j k l m n o p q r s t u v Quaynor SD, Stradtman EW, Kim HG, Shen Y, Chorich LP, Schreihofer DA, Layman LC (July 2013). "Delayed puberty and estrogen resistance in a woman with estrogen receptor α variant". The New England Journal of Medicine. 369 (2): 164–71. doi:10.1056/NEJMoa1303611. PMC 3823379. PMID 23841731. 10. ^ Gene Therapy. Academic Press. 12 August 1997. pp. 344–. ISBN 978-0-08-058132-3. 11. ^ Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1392–. ISBN 978-1-60913-345-0. 12. ^ Mark Dennis; William Talbot Bowen; Lucy Cho (31 August 2016). Mechanisms of Clinical Signs - EPub3. Elsevier Health Sciences. pp. 599–. ISBN 978-0-7295-8561-3. 13. ^ William T. O'Donohue; Lorraine T. Benuto; Lauren Woodward Tolle (8 July 2014). Handbook of Adolescent Health Psychology. Springer Science & Business Media. pp. 246–. ISBN 978-1-4614-6633-8. 14. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax Couse JF, Korach KS (1999). "Estrogen receptor null mice: what have we learned and where will they lead us?". Endocr. Rev. 20 (3): 358–417. doi:10.1210/edrv.20.3.0370. PMID 10368776. 15. ^ a b c Hill RA, Boon WC (2009). "Estrogens, brain, and behavior: lessons from knockout mouse models" (PDF). Semin. Reprod. Med. 27 (3): 218–28. doi:10.1055/s-0029-1216275. hdl:11343/57379. PMID 19401953. 16. ^ Hewitt SC, Harrell JC, Korach KS (2005). "Lessons in estrogen biology from knockout and transgenic animals". Annu. Rev. Physiol. 67: 285–308. doi:10.1146/annurev.physiol.67.040403.115914. PMID 15709960. 17. ^ Prossnitz ER, Hathaway HJ (2015). "What have we learned about GPER function in physiology and disease from knockout mice?". J. Steroid Biochem. Mol. Biol. 153: 114–26. doi:10.1016/j.jsbmb.2015.06.014. PMC 4568147. PMID 26189910. 18. ^ Alexander A, Irving AJ, Harvey J (2017). "Emerging roles for the novel estrogen-sensing receptor GPER1 in the CNS" (PDF). Neuropharmacology. 113 (Pt B): 652–660. doi:10.1016/j.neuropharm.2016.07.003. PMID 27392633. ## Further reading[edit] * Bulun SE (2014). "Aromatase and estrogen receptor α deficiency". Fertil. Steril. 101 (2): 323–9. doi:10.1016/j.fertnstert.2013.12.022. PMC 3939057. PMID 24485503. ## External links[edit] Classification D * ICD-10: E34.5 * OMIM: 300068 External resources * Orphanet: 99429 * v * t * e Gonadal disorder Ovarian * Polycystic ovary syndrome * Premature ovarian failure * Estrogen insensitivity syndrome * Hyperthecosis Testicular Enzymatic * 5α-reductase deficiency * 17β-hydroxysteroid dehydrogenase deficiency * aromatase excess syndrome Androgen receptor * Androgen insensitivity syndrome * Familial male-limited precocious puberty * Partial androgen insensitivity syndrome Other * Sertoli cell-only syndrome General * Hypogonadism * Delayed puberty * Hypergonadism * Precocious puberty * Hypoandrogenism * Hypoestrogenism * Hyperandrogenism * Hyperestrogenism * Postorgasmic illness syndrome * Cytochrome P450 oxidoreductase deficiency * Cytochrome b5 deficiency * Androgen-dependent condition * Aromatase deficiency * Complete androgen insensitivity syndrome * Mild androgen insensitivity syndrome * Hypergonadotropic hypogonadism * Hypogonadotropic hypogonadism * Fertile eunuch syndrome * Estrogen-dependent condition * Premature thelarche * Gonadotropin insensitivity * Hypergonadotropic hypergonadism * v * t * e Genetic disorders relating to deficiencies of transcription factor or coregulators (1) Basic domains 1.2 * Feingold syndrome * Saethre–Chotzen syndrome 1.3 * Tietz syndrome (2) Zinc finger DNA-binding domains 2.1 * (Intracellular receptor): Thyroid hormone resistance * Androgen insensitivity syndrome * PAIS * MAIS * CAIS * Kennedy's disease * PHA1AD pseudohypoaldosteronism * Estrogen insensitivity syndrome * X-linked adrenal hypoplasia congenita * MODY 1 * Familial partial lipodystrophy 3 * SF1 XY gonadal dysgenesis 2.2 * Barakat syndrome * Tricho–rhino–phalangeal syndrome 2.3 * Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome * Denys–Drash syndrome * Duane-radial ray syndrome * MODY 7 * MRX 89 * Townes–Brocks syndrome * Acrocallosal syndrome * Myotonic dystrophy 2 2.5 * Autoimmune polyendocrine syndrome type 1 (3) Helix-turn-helix domains 3.1 * ARX * Ohtahara syndrome * Lissencephaly X2 * MNX1 * Currarino syndrome * HOXD13 * SPD1 synpolydactyly * PDX1 * MODY 4 * LMX1B * Nail–patella syndrome * MSX1 * Tooth and nail syndrome * OFC5 * PITX2 * Axenfeld syndrome 1 * POU4F3 * DFNA15 * POU3F4 * DFNX2 * ZEB1 * Posterior polymorphous corneal dystrophy * Fuchs' dystrophy 3 * ZEB2 * Mowat–Wilson syndrome 3.2 * PAX2 * Papillorenal syndrome * PAX3 * Waardenburg syndrome 1&3 * PAX4 * MODY 9 * PAX6 * Gillespie syndrome * Coloboma of optic nerve * PAX8 * Congenital hypothyroidism 2 * PAX9 * STHAG3 3.3 * FOXC1 * Axenfeld syndrome 3 * Iridogoniodysgenesis, dominant type * FOXC2 * Lymphedema–distichiasis syndrome * FOXE1 * Bamforth–Lazarus syndrome * FOXE3 * Anterior segment mesenchymal dysgenesis * FOXF1 * ACD/MPV * FOXI1 * Enlarged vestibular aqueduct * FOXL2 * Premature ovarian failure 3 * FOXP3 * IPEX 3.5 * IRF6 * Van der Woude syndrome * Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 * Hyperimmunoglobulin E syndrome 4.3 * Holt–Oram syndrome * Li–Fraumeni syndrome * Ulnar–mammary syndrome 4.7 * Campomelic dysplasia * MODY 3 * MODY 5 * SF1 * SRY XY gonadal dysgenesis * Premature ovarian failure 7 * SOX10 * Waardenburg syndrome 4c * Yemenite deaf-blind hypopigmentation syndrome 4.11 * Cleidocranial dysostosis (0) Other transcription factors 0.6 * Kabuki syndrome Ungrouped * TCF4 * Pitt–Hopkins syndrome * ZFP57 * TNDM1 * TP63 * Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: * CREBBP * Rubinstein–Taybi syndrome Corepressor: * HR (Atrichia with papular lesions) *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Estrogen insensitivity syndrome

c3809250

wikipedia

https://en.wikipedia.org/wiki/Estrogen_insensitivity_syndrome

{"umls": ["C3809250"], "orphanet": ["785"], "wikidata": ["Q5401847"]}

A number sign (#) is used with this entry because of evidence that short-rib thoracic dysplasia-14 with polydactyly (SRTD14) is caused by homozygous mutation in the KIAA0586 gene (610178) on chromosome 14q23. Description Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia with or without polydactyly, see SRTD1 (208500). Clinical Features Alby et al. (2015) described 4 unrelated families with a lethal ciliopathy syndrome. In a consanguineous Lebanese family, the mother had 4 spontaneous abortions before 10 weeks' gestation, followed by a female infant born at term who died a few hours after birth. A subsequent pregnancy miscarried at 15 weeks, and examination of the fetus revealed severe hydrocephaly, cleft palate, postaxial polydactyly of all 4 limbs, right diaphragmatic hernia, and absence of clavicle bones; information about other skeletal abnormalities was not available. Another pregnancy was terminated at 15 weeks' gestation; prenatal ultrasound showed hydrops, and the fetus had hydrocephaly with occipital bone defect, cleft palate, preaxial polydactyly of all 4 limbs with polysyndactyly of the hands, and flat and wide iliac wings. In a Romanian family, in which the parents were distantly related, a first child was born healthy. However, the second pregnancy was terminated at 29 weeks' gestation after fetal ultrasound revealed hydramnios, micromelia, short ribs, small thorax, and hydrocephaly with vermis hypoplasia and agenesis of corpus callosum. Macroscopic examination showed cleft palate with multiple frenula and tongue hamartomas, narrow thorax with lung hypoplasia, preaxial polysyndactyly of the feet, and postaxial polydactyly of the hands. Neuropathologic examination showed olfactory bulb agenesis, vermian hypoplasia, and prerolandic polymicrogyria. A similarly affected third infant died 1 hour after birth. In a Hungarian family, an anencephalic fetus spontaneously aborted before 10 weeks' gestation. Their second child was a girl who required ventilatory support from birth and died at age 13 months. She had a small and narrow chest, short arms and legs, postaxial polydactyly of the hands, and duplication of the left hallux. Dysmorphic features included dysplastic and low-set ears, depressed nasal bridge, short upper lip that was bound down by multiple small frenula, hypoplastic gums, and short neck. She was unresponsive to visual stimuli and had small optic disc and retinal coloboma bilaterally. There was no response to acoustic stimuli and brainstem auditory evoked potential test showed no recognizable waves. She exhibited generalized hypotonia, lack of spontaneous movements, and reduced deep tendon reflexes. Brain MRI at 6 months showed a small brain with large ventricles and subarachnoid spaces, reduced white matter, cerebellar and medullary hypoplasia, large fourth ventricle, and the molar tooth sign on axial slices. X-rays showed narrow, elongated thorax with short ribs and short long bones. In a family from Kosovo, 2 affected males were born to distantly related parents. One patient died 1 day after birth, with a phenotype said to be identical to that of his brother. The second pregnancy was terminated at 26 weeks' gestation, and autopsy showed cleft palate, lingual hamartomas, occipital keyhole defect, narrow thorax with lung hypoplasia, postaxial polydactyly and brachyphalangy of the hands, preaxial polydactyly of the right foot, postaxial polydactyly of the left foot, and micropenis. X-rays revealed short ribs and micromelia, with round femoral ends and curved forearm bones. Neuropathologic examination showed corpus callosum agenesis with Probst bundles, vermis hypoplasia with the molar tooth sign, temporal polymicrogyria, and retinal coloboma. Molecular Genetics In a consanguineous Lebanese family in which 2 fetuses exhibited features similar to those of hydrolethalus syndrome (see 236680), including severe hydrocephaly, polydactyly, and skeletal abnormalities, Alby et al. (2015) sequenced the HYLS1 (610693) and KIF7 (611254) genes but found no mutations. Next-generation sequencing targeting 1,221 candidate ciliary genes identified homozygosity for a nonsense mutation in the KIAA0586 gene (S77X; 610178.0006) that segregated with disease and was not found in 300 Lebanese control chromosomes or in the dbSNP, Exome Variant Server, or ExAC databases. Additional next-generation sequencing of ciliary genes in 150 individuals with lethal ciliopathies and various combinations of brain and skeletal abnormalities identified 3 patients from 3 unrelated Eastern European families with cerebral anomalies, polydactyly, and long-bone shortening, including short ribs, who were all homozygous for the same splice variant in KIAA0586 (610178.0007). Haplotype analysis in the Romanian, Hungarian, and Kosovan families was consistent with a common ancestor, estimated to have lived 16 generations (480 years) earlier. INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Dysplastic ears \- Low-set ears \- No response to acoustic stimuli \- No recognizable waves on brainstem auditory evoked potential test Eyes \- No response to visual stimuli \- Retinal coloboma \- Small optic disc Nose \- Depressed nasal bridge Mouth \- Cleft palate \- Multiple frenula \- Multiple tongue hamartomas \- Hypoplastic gums Teeth \- Delayed dentition Neck \- Short neck CARDIOVASCULAR Heart \- Atrial septal defect RESPIRATORY Lung \- Lung hypoplasia CHEST External Features \- Narrow thorax Ribs Sternum Clavicles & Scapulae \- Short ribs \- Absent clavicles Diaphragm \- Diaphragmatic hernia GENITOURINARY External Genitalia (Male) \- Micropenis SKELETAL Skull \- Occipital defect Pelvis \- Wide flat iliac wing Limbs \- Micromelia \- Rounded ends of femurs Hands \- Postaxial polydactyly \- Preaxial polydactyly \- Polysyndactyly \- Brachyphalangy (in some patients) Feet \- Postaxial polydactyly \- Preaxial polydactyly \- Preaxial polysyndactyly \- Hallux duplication NEUROLOGIC Central Nervous System \- Generalized hypotonia \- No spontaneous movements \- Decreased deep tendon reflexes \- Small brain \- Anencephaly \- Hydrocephaly \- Large ventricles \- Large subarachnoid spaces \- Decreased white matter volume \- Hypoplasia or aplasia of corpus callosum \- Olfactory bulb agenesis \- Cerebellar vermis hypoplasia \- Medulla hypoplasia \- Molar tooth sign \- Polymicrogyria \- Abnormal cortical gyration pattern PRENATAL MANIFESTATIONS \- Hydrops fetalis (rare) Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Affected fetuses frequently undergo spontaneous abortion \- Variable phenotypic features cataloged depending on development of fetus or infant \- Term infants generally die within hours of birth, but 1 patient was kept alive for 13 months with ventilatory support MOLECULAR BASIS \- Caused by mutation in the KIAA0568 gene (KIAA0586, 610178.0006 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

SHORT-RIB THORACIC DYSPLASIA 14 WITH POLYDACTYLY

c4225286

omim

https://www.omim.org/entry/616546

{"doid": ["0110096"], "omim": ["616546"], "orphanet": ["397715"], "synonyms": ["JBTS with JATD", "Joubert syndrome with JATD"]}

A rare syndrome characterised by moderate to severe intellectual deficit, short stature, macrocephaly, and characteristic facies. It has been described in 11 males and three females from three successive generations of the same family. The males also presented with postpubertal macroorchidism. Transmission is X-linked. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Atkin-Flaitz syndrome

c0796206

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1193

{"gard": ["3537"], "mesh": ["C538195"], "omim": ["300431"], "umls": ["C0796206"], "icd-10": ["Q87.8"], "synonyms": ["X-linked intellectual disability, Atkin type"]}

Becker's nevus Becker's nevus on the left shoulder SpecialtyUnknown Becker's nevus (also known as "Becker's melanosis", "Becker's pigmentary hamartoma", "nevoid melanosis", and "pigmented hairy epidermal nevus"[1]) is a skin disorder predominantly affecting males.[2]:687 The nevus can be present at birth, but more often shows up around puberty.[3] It generally first appears as an irregular pigmentation (melanosis or hyperpigmentation) on the torso or upper arm (though other areas of the body can be affected), and gradually enlarges irregularly, becoming thickened and often hairy (hypertrichosis). The nevus is due to an overgrowth of the epidermis, pigment cells (melanocytes), and hair follicles.[4] This form of nevus was first documented in 1948 by American dermatologist Samuel William Becker (1894–1964).[5] ## Contents * 1 Clinical information * 2 Prevalence * 3 Malignancy * 4 Treatment * 5 See also * 6 References * 7 External links ## Clinical information[edit] Medical knowledge and documentation of this disorder is poor, likely due to a combination of factors including recent discovery, low prevalence, and the more or less aesthetic nature of the effects of the skin disorder. Thus the pathophysiology of Becker's nevus remains unclear. While it is generally considered an acquired rather than congenital disorder, there exists at least one case report documenting what researchers claim is a congenital Becker's nevus with genetic association: a 16-month-old boy with a hyperpigmented lesion on his right shoulder whose father has a similar lesion on his right shoulder.[6] ## Prevalence[edit] The most extensive study to date, a 1981 survey of nearly 20,000 French males aged 17 to 26,[7] served to disprove many commonly held beliefs about the disorder. In the French study, 100 subjects were found to have Becker's nevi, revealing a prevalence of 0.52%. Nevi appeared in one half the subjects before the age of 10, and between ages 10 and 20 in the rest. In one quarter of cases sun exposure seems to have played a role, a number apparently lower than that expected by researchers. Also surprising to researchers was the low incidence (32%) of Becker's nevi above the nipples, for it had generally been believed that the upper chest and shoulder area was the predominant site of occurrence. Pigmentation was light brown in 75% of cases (note: subjects were Caucasian), and average size of the nevus was 125 cm² (19 in²). ## Malignancy[edit] A 1991 report documented the cases of nine patients with both Becker's nevus and malignant melanoma.[8] Of the nine melanomas, five were in the same body area as the Becker's nevus, with only one occurring within the nevus itself. As this was apparently the first documented co-occurrence of the two diseases, there is so far no evidence of higher malignancy rates in Becker's nevi versus normal skin. Nonetheless, as with any abnormal skin growth, the nevus should be monitored regularly and any sudden changes in appearance brought to the attention of one's doctor. ## Treatment[edit] As Becker's nevus is considered a benign lesion, treatment is generally not necessary except for cosmetic purposes. Shaving or trimming can be effective in removing unwanted hair, while electrology or laser hair removal may offer a longer-lasting solution. Different types of laser treatments may also be effective in elimination or reduction of hyperpigmentation, though the results of laser treatments for both hair and pigment reduction appear to be highly variable. ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 1715. ISBN 1-4160-2999-0. 2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 3. ^ "Becker's nevus | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-24. 4. ^ Ngan, Vanessa. http://www.dermnetnz.org/lesions/beckers-naevus.html 5. ^ synd/774 at Who Named It? 6. ^ Book SE, Glass AT, Laude TA (1997). "Congenital Becker's nevus with a familial association". Pediatr Dermatol. 14 (5): 373–5. PMID 9336809. 7. ^ Tymen R, Forestier JF, Boutet B, Colomb D (1981). "[Late Becker's nevus. One hundred cases (author's transl)]". Ann Dermatol Venereol (in French). 108 (1): 41–6. PMID 7235503. 8. ^ Fehr B, Panizzon RG, Schnyder UW (1991). "Becker's nevus and malignant melanoma". Dermatologica. 182 (2): 77–80. doi:10.1159/000247749. PMID 2050238. ## External links[edit] Classification D * ICD-10: D22.5 (ILDS Q82.582) * ICD-9-CM: 216 * OMIM: 604919 * MeSH: C565735 * DiseasesDB: 31362 External resources * eMedicine: derm/48 * v * t * e Skin cancer of nevi and melanomas Melanoma * Mucosal melanoma * Superficial spreading melanoma * Nodular melanoma * lentigo * Lentigo maligna/Lentigo maligna melanoma * Acral lentiginous melanoma * Amelanotic melanoma * Desmoplastic melanoma * Melanoma with features of a Spitz nevus * Melanoma with small nevus-like cells * Polypoid melanoma * Nevoid melanoma * Melanocytic tumors of uncertain malignant potential Nevus/ melanocytic nevus * Nevus of Ito/Nevus of Ota * Spitz nevus * Pigmented spindle cell nevus * Halo nevus * Pseudomelanoma * Blue nevus * of Jadassohn–Tièche * Cellular * Epithelioid * Deep penetrating * Amelanotic * Malignant * Congenital melanocytic nevus (Giant * Medium-sized * Small-sized) * Balloon cell nevus * Dysplastic nevus/Dysplastic nevus syndrome * Acral nevus * Becker's nevus * Benign melanocytic nevus * Nevus spilus *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Becker's nevus

c0263579

wikipedia

https://en.wikipedia.org/wiki/Becker%27s_nevus

{"gard": ["3856", "5901"], "mesh": ["C565735"], "umls": ["C0263579", "C1858042"], "icd-9": ["216"], "icd-10": ["D22.5"], "orphanet": ["64755"], "wikidata": ["Q813705"]}

Léri-Weill dyschondrosteosis is a disorder of bone growth. Affected individuals typically have shortening of the long bones in the arms and legs (mesomelia). As a result of the shortened leg bones, people with Leri-Weill dyschondrosteosis typically have short stature. Most people with the condition also have an abnormality of the wrist and forearm bones called Madelung deformity, which may cause pain and limit wrist movement. This abnormality usually appears in childhood or early adolescence. Other features of Léri-Weill dyschondrosteosis can include increased muscle mass (muscle hypertrophy); bowing of a bone in the lower leg called the tibia; a greater-than-normal angling of the elbow away from the body (increased carrying angle); and a high arched palate. Léri-Weill dyschondrosteosis occurs in both males and females, although its signs and symptoms tend to be more severe in females. Researchers believe that the more severe features may result from hormonal differences. ## Frequency The prevalence of Léri-Weill dyschondrosteosis is unknown. It is diagnosed more often in females than in males. ## Causes Most cases of Léri-Weill dyschondrosteosis result from changes involving the SHOX gene. The protein produced from this gene plays a role in bone development and is particularly important for the growth and maturation of bones in the arms and legs. The most common cause of Léri-Weill dyschondrosteosis is a deletion of the entire SHOX gene. Other genetic changes that can cause the disorder include mutations in the SHOX gene or deletions of nearby genetic material that normally helps regulate the gene's activity. These changes reduce the amount of SHOX protein that is produced. A shortage of this protein disrupts normal bone development and growth, which underlies the major features of Léri-Weill dyschondrosteosis. In affected people who do not have a genetic change involving the SHOX gene, the cause of the condition is unknown. ### Learn more about the gene associated with Léri-Weill dyschondrosteosis * SHOX ## Inheritance Pattern Léri-Weill dyschondrosteosis has a pseudoautosomal dominant pattern of inheritance. The SHOX gene is located on both the X and Y chromosomes (sex chromosomes) in an area known as the pseudoautosomal region. Although many genes are unique to either the X or Y chromosome, genes in the pseudoautosomal region are present on both sex chromosomes. As a result, both females (who have two X chromosomes) and males (who have one X and one Y chromosome) normally have two functional copies of the SHOX gene in each cell. The inheritance pattern of Léri-Weill dyschondrosteosis is described as dominant because one missing or altered copy of the SHOX gene in each cell is sufficient to cause the disorder. In females, the condition results when the gene is missing or altered on one of the two copies of the X chromosome; in males, it results when the gene is missing or altered on either the X chromosome or the Y chromosome. A related skeletal disorder called Langer mesomelic dysplasia occurs when both copies of the SHOX gene are mutated in each cell. This disorder has signs and symptoms that are similar to, but typically more severe than, those of Léri-Weill dyschondrosteosis. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Léri-Weill dyschondrosteosis

c0152441

medlineplus

https://medlineplus.gov/genetics/condition/leri-weill-dyschondrosteosis/

{"gard": ["3224"], "mesh": ["C562398"], "omim": ["127300"], "synonyms": []}

Disseminated superficial actinic porokeratosis A porokeratosis lesion in a patient with disseminated superficial actinic porokeratosis. SpecialtyDermatology Disseminated superficial actinic porokeratosis (DSAP) is a non-contagious skin condition with apparent genetic origin in the SART3 gene.[1]:533 It most often presents in sun-exposed areas of the body. Some DSAP cases have been reported in patients with acute immune compromised situations, particularly in the elderly. For those with sun damaged skin, the lesions usually begin to appear in the patient's 20s and increase in number and visibility in the 40s or 50s. Commonly, though not always, the number and visibility of lesions is in direct proportion to the amount of sun damage to the affected area. Lesions generally are characterized by an irregularly shaped thread-like ring that is usually the size of a pencil eraser, though lesions vary and may be half or double that size. The thread-like ring is very thin, much like fabric thread for sewing, and raised such that it is both palpable and visible. The interior of the ring may be rough like sandpaper, or smooth. The interior is often discolored, though colors vary from patient to patient. Lesions, due to their vascular nature, can also vary according to body temperature, environmental temperatures, and other external stimuli. The internal ring color is most often reddish, purplish, pink, or brown.[2] Some patients report itching and irritation associated with the condition, and many report no notable sensation. Although no known hormonal link has been found, DSAP occurs more commonly in women.[3] A study in 2000 was done on a Chinese family, in which a locus for a gene was located.[4] ## See also[edit] * Porokeratosis * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ Freedberg, Irwin M.; Fitzpatrick, Thomas B. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). New York: McGraw-Hill, Medical Pub. Division. p. 533. ISBN 0-07-138076-0. 2. ^ "Yahoo! Groups". 3. ^ "Disseminated Superficial Actinic Porokeratosis - American Osteopathic College of Dermatology (AOCD)". 4. ^ Xia JH, Yang YF, Deng H, et al. (June 2000). "Identification of a locus for disseminated superficial actinic porokeratosis at chromosome 12q23.2-24.1". J. Invest. Dermatol. 114 (6): 1071–4. doi:10.1046/j.1523-1747.2000.00978.x. PMID 10844547. ## External links[edit] Classification D * OMIM: 175900 607728 612293 612353 * DiseasesDB: 33407 External resources * Orphanet: 79152 This Genodermatoses article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Disseminated superficial actinic porokeratosis

c0162839

wikipedia

https://en.wikipedia.org/wiki/Disseminated_superficial_actinic_porokeratosis

{"gard": ["10983"], "mesh": ["D017499"], "umls": ["C0162839", "C0265970"], "orphanet": ["79152"], "wikidata": ["Q5282749"]}

A number sign (#) is used with this entry because of evidence that 46,XX male sex reversal can be caused by genomic duplications or deletions in the SOX3 (313430) regulatory region on chromosome Xq26. Clinical Features Sutton et al. (2011) studied 3 46,XX SRY (480000)-negative male sex reversal patients. Patient 'A' was a male of European descent who presented at age 30 years for evaluation of infertility, which was confirmed by azoospermia on 2 spermograms. He had no evidence of hypopituitarism or intellectual disability, and had normal-appearing secondary sexual characteristics. Patient 'B' was a 35-year-old of European descent, who had gender dysphoria reported from around 6 years of age, leading to gender reassignment surgery at age 26 years. On examination at age 25 years, external genitalia were noted to be normal male except for small, soft testes, measuring less than 4 ml by orchidometer. Postsurgical histology showed atrophic changes in the testes, with loss of normal spermatogenesis, thickening and hyalinization of the tubular basal lamina, and diminished numbers of interstitial cells. Spermatic cords were histologically normal, as was the penis. Patients A and B both underwent puberty at around 14 years of age. Patient 'C' was a boy of Mexican origin who presented at 19 months of age with failure to thrive and developmental delay; he had microcephaly and a hypoplastic scrotum with retractile testes. Molecular Genetics Sutton et al. (2011) screened a cohort of 16 SRY (480000)-negative 46,XX male patients for copy number variation (CNV) and identified rearrangements encompassing or in close proximity to the SOX3 gene in 3 patients. Patient A had tandem microduplications of approximately 123 kb and 85 kb, respectively, with the larger spanning the entire SOX3 gene. There was no evidence for skewed inactivation of the X chromosome. Patient B had a single 343-kb microdeletion immediately upstream of SOX3, suggesting that altered regulation rather than increased dosage of SOX3 is the cause of XX male sex reversal. Patient C, who had a more complex phenotype including microcephaly, developmental delay, and growth retardation, had a large, approximately 6-Mb duplication that encompassed SOX3 and at least 18 additional distally located genes. INHERITANCE \- X-linked dominant GENITOURINARY External Genitalia (Male) \- Normal-appearing male external genitalia in 46,XX individuals MOLECULAR BASIS \- Caused by duplications or deletions on Xq26 involving the Sry-box 3 gene (SOX3, 313430 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

46,XX SEX REVERSAL 3

c0432475

omim

https://www.omim.org/entry/300833

{"omim": ["300833"], "orphanet": ["393"], "synonyms": ["Alternative titles", "CHROMOSOME Xq26 DUPLICATION SYNDROME", "46,XX SEX REVERSAL, SOX3-RELATED"]}

disease of humans caused by mites "Rat mite dermatitis" redirects here. For similar conditions, see Acariasis. Rodent mite dermatitis Other namesRat mite dermatitis SpecialtyDermatology Rodent mite dermatitis (also known as rat mite dermatitis) is an often unrecognized ectoparasitosis occurring after human contact with haematophagous mesostigmatid mites that infest rodents, such has house mice,[1] rats[2] and hamsters.[3] The condition is associated with the tropical rat mite (Ornithonyssus bacoti), spiny rat mite (Laelaps echidnina) and house mouse mite (Liponyssoides sanguineus)[4] which opportunistically feed on humans. Rodent mites are capable of surviving for long periods without feeding and travelling long distances when seeking hosts.[4] Cases have been reported in homes, libraries,[5] hospitals[6] and care homes.[7] A similar condition, known as gamasoidosis, is caused by avian mites.[8] ## Contents * 1 Symptoms and signs * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 See also * 6 References ## Symptoms and signs[edit] Rodent mite bites leave multiple groups or individual small itchy papules (around 1–2 mm in diameter)[7] on the skin (papular urticaria).[9][10] These are found mostly "on the upper extremities, neck, upper trunk and face".[7] ## Diagnosis[edit] Diagnosis requires species identification of the parasite, which will be likely to be found in the environment of its host rather than on the hosts’ skin.[10] Rodent mites are very small, for O. bacoti "female mites reach a size between 0.75 and 1.40 mm, males are a little smaller".[7] ## Treatment[edit] The original rodent host of the mites must be located and eradicated,[11] and their nests removed.[12] Steps should also be taken to prevent future infestations, such as by blocking the rodents means of entry into the building. The patient's environment should then be treated,[10] using both non-residual and residual insecticides, mites crawling in the open can be removed by vacuuming or with a cloth moistened with alcohol.[12] Bites can be treated with antihistamines and corticosteroids, to relieve the associated itching and allergic reactions.[7] ## Epidemiology[edit] L. sanguineus has been implicated in the spread of Rickettsialpox.[13] ## See also[edit] * Acariasis * Gamasoidosis ## References[edit] 1. ^ Reeves, Will K.; Cobb, Kristin D. (2005-07-01). "Ectoparasites of House Mice (Mus musculus) from Pet Stores in South Carolina, U.S.A". Comparative Parasitology. 72 (2): 193–195. doi:10.1654/4178. ISSN 1525-2647. S2CID 85650971. 2. ^ Engel, Peter M.; Welzel, J.; Maass, M.; Schramm, U.; Wolff, H. H. (1998). "Tropical Rat Mite Dermatitis: Case Report and Review". Clinical Infectious Diseases. 27 (6): 1465–1469. doi:10.1086/515016. ISSN 1058-4838. PMID 9868661. 3. ^ Creel, Naomi B.; Crowe, Mark A.; Mullen, Gary R. (2003). "Pet hamsters as a source of rat mite dermatitis". Cutis. 71 (6): 457–461. ISSN 0011-4162. PMID 12839256. 4. ^ a b Watson, J. (2008-01-01). "New Building, Old Parasite: Mesostigmatid Mites--An Ever-Present Threat to Barrier Rodent Facilities". ILAR Journal. 49 (3): 303–309. doi:10.1093/ilar.49.3.303. ISSN 1084-2020. PMC 7108606. PMID 18506063. 5. ^ Chung, Sang Lip; Hwang, Sung Joo; Kwon, Soon Baek; Kim, Do Won; Jun, Jae Bok; Cho, Baik Kee (1998). "Outbreak of rat mite dermatitis in medical students". International Journal of Dermatology. 37 (8): 591–594. doi:10.1046/j.1365-4362.1998.00558.x. ISSN 0011-9059. PMID 9732004. 6. ^ Haggard, Carl N. (1955-03-01). "Rat Mite Dermatitis in Children". Pediatrics. 15 (3): 322–324. ISSN 0031-4005. PMID 14356805. 7. ^ a b c d e Baumstark, J.; Beck, W.; Hofmann, H. (2007). "Outbreak of Tropical Rat Mite (Ornithonyssus bacoti) Dermatitis in a Home for Disabled Persons" (PDF). Dermatology. 215 (1): 66–68. doi:10.1159/000102037. ISSN 1018-8665. PMID 17587843. S2CID 3124223. 8. ^ Kowalska, M.; Kupis, B. (1976). "Gamasoidosis (gamasidiosis)-not infrequent skin reactions, frequently unrecognized". Polish Medical Sciences and History Bulletin. 15–16 (4): 391–394. ISSN 0301-0236. PMID 826895. 9. ^ Engel, P. M.; Welzel, J.; Maass, M.; Schramm, U.; Wolff, H. H. (1998). "Tropical rat mite dermatitis: case report and review". Clinical Infectious Diseases. 27 (6): 1465–1469. doi:10.1086/515016. ISSN 1058-4838. PMID 9868661. 10. ^ a b c Beck, W. (2007-11-01). "Tropical Rat Mites as newly emerging disease pathogens in rodents and man". Travel Medicine and Infectious Disease. 5 (6): 403. doi:10.1016/j.tmaid.2007.09.016. ISSN 1477-8939. 11. ^ Fox, James G. (1982-09-01). "Outbreak of Tropical Rat Mite Dermatitis in Laboratory Personnel". Archives of Dermatology. 118 (9): 676–8. doi:10.1001/archderm.1982.01650210056019. ISSN 0003-987X. PMID 7114872. 12. ^ a b "Parasitic Mites of Humans | Entomology". entomology.ca.uky.edu. Retrieved 2018-06-05. 13. ^ Azad, A. F.; Beard, C. B. (1998). "Rickettsial pathogens and their arthropod vectors". Emerging Infectious Diseases. 4 (2): 179–186. doi:10.3201/eid0402.980205. PMC 2640117. PMID 9621188. * v * t * e Mite-borne diseases and infestations Infestations * Acariasis * Baker's itch * Cheyletiellosis * Demodicosis * Feather pillow dermatitis * Gamasoidosis * Grain itch * Grocer's itch * Rodent mite dermatitis * Scabies * Trombiculosis Other diseases * House dust mite allergy * Oral mite anaphylaxis * List of mites associated with cutaneous reactions Species and bites Trombidiformes * Demodex brevis / Demodex folliculorum * demodicosis * Demodex mite bite * Trombicula * trombiculosis * Pyemotes herfsi * Cheyletiella (cheyletiellosis) * Leptotrombidium deliense Sarcoptiformes * Sarcoptes scabiei * scabies Mesostigmata * Dermanyssus gallinae * gamasoidosis * Liponyssoides sanguineus * rickettsialpox Other * House dust mite *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Rodent mite dermatitis

None

wikipedia

https://en.wikipedia.org/wiki/Rodent_mite_dermatitis

{"wikidata": ["Q56289962"]}

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of heart disease that usually appears in adulthood. ARVC is a disorder of the myocardium, which is the muscular wall of the heart. This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death. ARVC may not cause any symptoms in its early stages. However, affected individuals may still be at risk of sudden death, especially during strenuous exercise. When symptoms occur, they most commonly include a sensation of fluttering or pounding in the chest (palpitations), light-headedness, and fainting (syncope). Over time, ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen. If the myocardium becomes severely damaged in the later stages of the disease, it can lead to heart failure. ## Frequency ARVC occurs in an estimated 1 in 1,000 to 1 in 1,250 people. This disorder may be underdiagnosed because it can be difficult to detect in people with mild or no symptoms. ## Causes ARVC can result from mutations in at least 13 genes. Many of these genes are known as desmosomal genes because they provide instructions for making components of cell structures called desmosomes. Desmosomes attach heart muscle cells to one another, providing strength to the myocardium and playing a role in signaling between neighboring cells. Mutations in desmosomal genes impair the function of desmosomes. Without normal desmosomes, cells of the myocardium detach from one another and die, particularly when the heart muscle is placed under stress (such as during vigorous exercise). These changes primarily affect the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. The damaged myocardium is gradually replaced by fat and scar tissue. As this abnormal tissue builds up, the walls of the right ventricle become stretched out, preventing the heart from pumping blood effectively. These changes also disrupt the electrical signals that control the heartbeat, which can lead to arrhythmia. Less commonly, mutations in non-desmosomal genes can cause ARVC. These genes have a variety of functions, including cell signaling, providing structure and stability to heart muscle cells, and helping to maintain a normal heart rhythm. Researchers are working to determine how mutations in non-desmosomal genes can lead to ARVC. Gene mutations have been found in about 60 percent of people with ARVC. Mutations in a desmosomal gene called PKP2 appear to be most common. In people without an identified mutation, the cause of the disorder is unknown. Researchers are looking for additional genetic factors that play a role in causing ARVC. ### Learn more about the genes associated with Arrhythmogenic right ventricular cardiomyopathy * DES * DSC2 * DSP * JUP * LMNA * PKP2 * RYR2 * TGFB3 * TTN Additional Information from NCBI Gene: * CTNNA3 * DSG2 * PLN * TMEM43 ## Inheritance Pattern Up to half of all cases of ARVC appear to run in families. Most familial cases of the disease have an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Rarely, ARVC has an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Arrhythmogenic right ventricular cardiomyopathy

c1862511

medlineplus

https://medlineplus.gov/genetics/condition/arrhythmogenic-right-ventricular-cardiomyopathy/

{"gard": ["5847"], "mesh": ["C566254"], "omim": ["107970", "610193", "610476", "611528", "615616", "600996", "602086", "602087", "604400", "604401", "607450", "609040"], "synonyms": []}

A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-2B (DFNA2B) is caused by mutation in the GJB3 gene (603324) on chromosome 1p34.3 See also DFNA2A (600101), which is caused by mutation in the KCNQ4 gene (603537) on chromosome 1p34.2. Clinical Features Xia et al. (1998) reported 2 unrelated Chinese families with autosomal dominant hearing loss. The deafness was characterized by progressive high frequency hearing loss in adulthood, with milder expression in females. Molecular Genetics In affected members of 2 Chinese families with autosomal dominant hearing loss, Xia et al. (1998) identified heterozygous mutations in the GJB3 gene (603324.0004; 603324.0005). INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Hearing loss, bilateral high-frequency, sensorineural MOLECULAR BASIS \- Caused by mutation in the gap junction protein, beta-3 gene (GJB3, 603324.0004 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

DEAFNESS, AUTOSOMAL DOMINANT 2B

c2675236

omim

https://www.omim.org/entry/612644

{"doid": ["0110559"], "mesh": ["C567214"], "omim": ["612644"], "orphanet": ["90635"], "synonyms": ["Autosomal dominant isolated neurosensory deafness type DFNA", "Autosomal dominant isolated neurosensory hearing loss type DFNA", "Autosomal dominant isolated sensorineural deafness type DFNA", "Autosomal dominant isolated sensorineural hearing loss type DFNA", "Autosomal dominant non-syndromic neurosensory deafness type DFNA", "Autosomal dominant non-syndromic neurosensory hearing loss type DFNA", "Autosomal dominant non-syndromic sensorineural hearing loss type DFNA"], "genereviews": ["NBK1434"]}

Hepatic veno-occlusive disease with immunodeficiency (also called VODI) is a hereditary disorder of the liver and immune system. Its signs and symptoms appear after the first few months of life. Hepatic veno-occlusive disease is a condition that blocks (occludes) small veins in the liver, disrupting blood flow in this organ. This condition can lead to enlargement of the liver (hepatomegaly), a buildup of scar tissue (hepatic fibrosis), and liver failure. Children with VODI are prone to recurrent infections caused by certain bacteria, viruses, and fungi. The organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people. These infections are usually serious and may be life-threatening. In most people with VODI, infections occur before hepatic veno-occlusive disease becomes evident. Many people with VODI live only into childhood, although some affected individuals have lived to early adulthood. ## Frequency VODI appears to be a rare disorder; approximately 20 affected families have been reported worldwide. Most people diagnosed with the condition have been of Lebanese ancestry. However, the disorder has also been identified in several individuals with other backgrounds in the United States and Italy. ## Causes VODI results from mutations in the SP110 gene. This gene provides instructions for making a protein called SP110 nuclear body protein, which is involved in the normal function of the immune system. This protein likely helps regulate the activity of genes needed for the body's immune response to foreign invaders (such as viruses and bacteria). Mutations in the SP110 gene prevent cells from making functional SP110 nuclear body protein, which impairs the immune system's ability to fight off infections. It is unclear how a lack of this protein affects blood flow in the liver. ### Learn more about the gene associated with Hepatic veno-occlusive disease with immunodeficiency * SP110 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Hepatic veno-occlusive disease with immunodeficiency

c1856128

medlineplus

https://medlineplus.gov/genetics/condition/hepatic-veno-occlusive-disease-with-immunodeficiency/

{"gard": ["10083"], "mesh": ["C537257"], "omim": ["235550"], "synonyms": []}

A number sign (#) is used with this entry because of evidence that familial adult myoclonic epilepsy-6 (FAME6) is caused by a heterozygous 5-bp repeat expansion (TTTCA(n)) in the TNRC6A gene (610739) on chromosome 16p12. One such family has been reported. For a phenotypic description and a discussion of genetic heterogeneity of familial adult myoclonic epilepsy, see FAME1 (601068). Clinical Features Ishiura et al. (2018) reported a 4-generation Japanese family (F9283) with familial adult myoclonic epilepsy. Clinical details were limited. The age at onset of myoclonic tremor ranged from the early twenties to the seventies. In 1 patient, a giant SEP was observed. None of the patients in the family experienced seizures, although 1 patient showed borderline findings on electroencephalogram. Inheritance The transmission pattern of FAME6 in the family reported by Ishiura et al. (2018) was consistent with autosomal dominant inheritance. Molecular Genetics In 5 affected members of a multigenerational family (F9283) with FAME6, Ishiura et al. (2018) identified a heterozygous 5-bp TTTCA(n) repeat in the upstream noncoding region of exon 1 of the TNRC6A gene (610739.0001). This expansion was located between two 5-bp TTTTA(n) repeats. TTTCA(n) repeat expansions were not found in the reference sequence or in 1,000 control individuals. TTTTA(n) expanded repeats were found in 0.9% of controls, suggesting that the TTTCA(n) expansion is responsible for the phenotype. The mutation was found by searching for repeat motifs using data from whole-genome sequence analysis and Southern blot analysis after a similar repeat expansion was identified in the SAMD12 gene (618073) in patients with FAME1. Functional studies of the TNRC6A variant and studies of patient cells were not performed, but based on studies with SAMD12, Ishiura et al. (2018) postulated that the expression of RNA molecules containing expansions of UUUCA and UUUUA repeats per se is involved in the pathogenesis of the disorder, rather than altered physiologic function of each individual gene. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

EPILEPSY, FAMILIAL ADULT MYOCLONIC, 6

None

omim

https://www.omim.org/entry/618074

{"omim": ["618074"], "synonyms": ["Alternative titles", "BENIGN ADULT FAMILIAL MYOCLONIC EPILEPSY 6", "CORTICAL MYOCLONIC TREMOR WITH EPILEPSY, FAMILIAL, 6"]}

A number sign (#) is used with this entry because of evidence that sessile serrated polyposis cancer syndrome (SSPCS) is caused by heterozygous mutation in the RNF43 gene (612482) on chromosome 17q22. Description Sessile serrated polyposis cancer syndrome (SSPCS) is a rare disorder characterized by the presence of multiple serrated polyps in the colon and an increased personal and familial risk of colorectal cancer. SSPCS is defined by the World Health Organization (WHO) as the presence of at least 5 sessile serrated polyps (also known as 'sessile serrated adenomas,' or SSAs) proximal to the sigmoid colon, with 2 or more that are greater than 10 mm in diameter; or any number of serrated polyps in a person with a first-degree relative with SSPCS; or more than 20 serrated polyps of any size, distributed throughout the colon. SSAs are found in 2% of average-risk individuals undergoing their first screening colonoscopy, and are estimated to be responsible for 20 to 35% of all colon cancers. SSAs exhibit somatic mutations in the BRAF gene (164757), or less commonly in the KRAS gene (190070), early in their development. Individuals with SSPCS have a lifetime risk of colon cancer as high as 54% and may have a strong personal or family history of extracolonic cancers; first-degree relatives have a 32% risk of developing multiple serrated polyps and a 5-fold increased risk of colon cancer. An increased risk of pancreatic cancer has also been observed (summary by Gala et al., 2014). Clinical Features Gala et al. (2014) studied 2 women with serrated polyposis, both of whom met the WHO criteria for SSPCS and had a mutation in the RNF43 gene (see MOLECULAR GENETICS). The first was a 62-year-old woman diagnosed at age 51 years. She had more than 30 serrated polyps throughout the colon, and her father had colon and prostate cancer. The second was a 62-year-old woman who developed chronic leukocytic leukemia at age 42 and was diagnosed with SSPCS at age 52. Her 3 sibs all had colonic polyps, and there was a strong family history of cancer: their father had kidney cancer and their mother had breast cancer, and their maternal and paternal aunts and uncles had a variety of cancers, including cancer of the breast, pancreas, stomach, bladder, and colon. Taupin et al. (2015) reported a family in which a brother and sister had SSPCS. The 23-year-old brother underwent emergency right hemicolectomy for an obstructing colorectal carcinoma (CRC) that arose from a serrated polyp and was negative for microsatellite instability. He had more than 50 large serrated polyps throughout the colon. His 27-year-old sister underwent screening colonoscopy, which revealed more than 20 large serrated polyps; she underwent elective subtotal colectomy, and more than 60 polyps were present in the resected specimen. Their 21-year-old brother had a single adenoma of the rectum on colonoscopy; follow-up colonoscopy a year later was normal. Their mother had died at age 50 years of pancreatic cancer; paternal family history was negative for polyposis or CRC in the father's generation. Molecular Genetics Gala et al. (2014) studied 20 probands with serrated polyposis, 16 of whom met the WHO criteria for SSPCS syndrome. A personal history of colon cancer was present in 3, whereas 11 had a family history of colon cancer, and 8 had 1 or more extracolonic neoplasms. The median age of the probands was 52, and the number of sessile serrated adenomas ranged from 3 to more than 50. The authors analyzed SSA tissue from 19 of the SSPCS probands and found that 18 of the genotyped SSAs carried the BRAF V600E mutation (164757.0001); 1 individual's tissue did not harbor an identifiable mutation in the BRAF or KRAS genes. Exome data from the 20 SSPCS probands was analyzed for 'strong' loss-of-function mutations (affecting all isoforms of a given gene) in 233 genes relevant to oncogene-induced senescence pathways in the colon, and germline nonsense or splice site mutations were identified in 5 participants, in the ATM (607585), TELO2 (611140), RBL1 (116957), XAF1 (606717), and PIF1 (610953) genes. Overall, 25% of probands harbored a mutation in that gene set compared to 9.87% of 4,300 control exomes from the Exome Variant Server database (OR, 3.0; p = 0.04). In the remaining 15 probands, the authors further analyzed the exome data for loss-of-function variants in genes at loci implicated by genomewide association studies of all cancers, and identified nonsense mutations in 4 individuals: 2 with a mutation in the ULK4 gene (617010), R862X (rs199884004), which was also found in 45 of the 4,300 control exomes (OR, 10.5; p = 0.02); and 2 with a mutation in the RNF43 gene (R113X; 612482.0001), found in 1 of the 4,300 control exomes (OR, 460; p = 6.8 x 10(-5)). Gala et al. (2014) concluded that germline loss-of-function variants in genes that regulate senescence pathways are associated with the development of multiple SSAs, and that nonsense mutations in RNF43 are associated with a high risk of developing SSAs. By exome sequencing in a 23-year-old man with SSPCS, who was negative for mutation in the MUTYH gene (604933) and who had developed colorectal carcinoma that was negative for somatic mutation at KRAS codons 12 and 13, Taupin et al. (2015) identified heterozygosity for a nonsense mutation in the RNF43 gene (R132X; 612482.0002). The mutation was present in the proband's affected sister, but was not found in their unaffected father or brother. DNA was unavailable from their mother, who died of pancreatic cancer at age 50 years. Inheritance Boparai et al. (2010) analyzed the incidence rate of colorectal cancer in first-degree relatives of patients with hyperplastic polyposis syndrome, who often have multiple sessile or traditional serrated adenomas, and compared this rate with that in the general population. A total of 347 first-degree relatives (41% male) from 57 pedigrees were included, contributing 11,053 person-years of follow-up. During the study period a total of 27 CRC cases occurred among first-degree relatives, compared to 5 expected CRC cases (p less than 0.001). The relative risk of colorectal cancer in first-degree relatives compared to the general population was 5.4 (95% CI, 3.7-7.8). Four first-degree relatives satisfied the criteria for hyperplastic polyposis syndrome. Based on the estimated HPS prevalence of 1 in 3,000 in the general population, the projected relative risk of HPS in first-degree relatives was 39 (95% CI, 13-121). Boparai et al. (2010) suggested that as long as no causative gene has been identified, screening colonoscopies of all first-degree relatives of patients with hyperplastic polyposis syndrome are warranted. Hazewinkel et al. (2015) evaluated the diagnostic yield of screening colonoscopies in 77 first-degree relatives of 36 probands with serrated polyposis. First-degree relatives had a median age of 52 years with an interquartile range of 41 to 60 years. Colorectal cancer was not diagnosed. One or more significant polyps were detected in 43% of first-degree relatives. No differences based on age, gender, or familial relationship were observed in the detection of polyps. Seven first-degree relatives (9%) had multiple polyps (5 or more); 11 (14%) first-degree relatives fulfilled serrated polyposis syndrome WHO criterion 2 (any number of serrated polyps proximal to the sigmoid colon in a first-degree relative of a patient with serrated polyposis syndrome), of whom 1 sib also met serrated polyposis syndrome WHO criterion 3 (greater than 20 serrated polyps spread throughout the colon). INHERITANCE \- Autosomal dominant ABDOMEN Gastrointestinal \- Multiple sessile serrated polyps throughout the colon NEOPLASIA \- Colorectal carcinoma, susceptibility to (in some patients) \- Extracolonic cancers, susceptibility to (in some patients) MISCELLANEOUS \- Four patients have been reported (last curated September 2016) MOLECULAR BASIS \- Caused by mutation in the ring finger protein-43 gene (RNF43, 612482.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

SESSILE SERRATED POLYPOSIS CANCER SYNDROME

c4310714

omim

https://www.omim.org/entry/617108

{"omim": ["617108"], "orphanet": ["157798"], "synonyms": ["Serrated polyposis"]}

EEM syndrome EEM syndrome has an autosomal recessive pattern of inheritance. SpecialtyMedical genetics EEM syndrome (or Ectodermal dysplasia, Ectrodactyly and Macular dystrophy syndrome)[1] is an autosomal recessive[2] congenital malformation disorder affecting tissues associated with the ectoderm (skin, hair, nails, teeth), and also the hands, feet and eyes.[1][3] ## Contents * 1 Presentation * 2 Pathophysiology * 3 Diagnosis * 4 Management * 5 See also * 6 References * 7 External links ## Presentation[edit] EEM syndrome exhibits a combination of prominent symptoms and features. These include: ectodermal dysplasia (systemic malformations of ectodermal tissues),[1] ectrodactyly ("lobster claw" deformity in the hands and feet),[3] macular dystrophy (a progressive eye disease),[2][3] syndactyly (webbed fingers or toes),[3] hypotrichosis (a type of hair-loss),[4] and dental abnormalities (hypodontia).[2] ## Pathophysiology[edit] EEM syndrome is caused by mutations in the P-cadherin gene (CDH3).[5] Distinct mutations in CDH3 (located on human chromosome 16) are responsible for the macular dystrophy and spectrum of malformations found in EEM syndrome,[5] due in part to developmental errors caused by the resulting inability of CDH3 to respond correctly to the P-cadherin transcription factor p63.[6] The gene for p63 (TP73L, found on human chromosome 3) may also play a role in EEM syndrome.[6] Mutations in this gene are associated with the symptoms of EEM and similar disorders, particularly ectrodactyly.[7] EEM syndrome is an autosomal recessive disorder,[2] which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - are required to inherit the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[citation needed] ## Diagnosis[edit] This section is empty. You can help by adding to it. (July 2017) ## Management[edit] This section is empty. You can help by adding to it. (July 2017) ## See also[edit] * Germ layer * Integumentary system * Hay-Wells syndrome ## References[edit] 1. ^ a b c Hayakawa M, Yanashima K, Kato K, Nakajima A, Yamauchi H (1989). "Association of ectodermal dysplasia, ectrodactyly and macular dystrophy: EEM syndrome (case report)". Ophthalmol Paediatr Genet. 10 (4): 287–292. doi:10.3109/13816818909009884. PMID 2628819. 2. ^ a b c d Yildirim MS, Ogun TC, Kamis U (2006). "Ectrodactyly, ectodermal dysplasia, macular degeneration syndrome: a further contribution". Genet Couns. 17 (2): 149–153. PMID 16970031. 3. ^ a b c d Senecky Y, Halpern GJ, Inbar D, Attias J, Shohat M (2001). "Ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM syndrome) in siblings". Am J Med Genet. 101 (3): 195–197. doi:10.1002/ajmg.1361. PMID 11424132. 4. ^ Balarin Silva V, Simones AM, Marques-de-Faria AP (1999). "EEM syndrome: report of a family and results of a ten-year follow-up". Am J Med Genet. 20 (2): 95–99. doi:10.1076/opge.20.2.95.2290. PMID 10420194. 5. ^ a b Kjaer KW, Hansen L, Schwabe GC, Marques-de-Faria AP, Eiberg H, Mundlos S, Tommerup N, Rosenberg T (2005). "Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome)". J Med Genet. 42 (4): 292–298. doi:10.1136/jmg.2004.027821. PMC 1736041. PMID 15805154. 6. ^ a b Shimomura Y, Wajid M, Shapiro L, Christiano AM (2008). "P-cadherin is a p63 target gene with a crucial role in the developing human limb bud and hair follicle". Development. 135 (4): 743–753. doi:10.1242/dev.006718. PMID 18199584. 7. ^ Zenteno JC, Berdon-Zapata V, Kofman-Alfaro S, Mutchinick O (2005). "Isolated ectrodactyly caused by a heterozygous missense mutation in the transactivation domain of Tp63". Am J Med Genet A. 134 (1): 74–76. doi:10.1002/ajmg.a.30277. PMID 15736220. ## External links[edit] Classification D * ICD-10: Q82.4 * ICD-9-CM: 757.31 * OMIM: 225280 * MeSH: C536190 * SNOMED CT: 720856002 External resources * Orphanet: 1897 * v * t * e Congenital malformations and deformations of integument / skin disease Genodermatosis Congenital ichthyosis/ erythrokeratodermia AD * Ichthyosis vulgaris AR * Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis * Lamellar ichthyosis * Harlequin-type ichthyosis * Netherton syndrome * Zunich–Kaye syndrome * Sjögren–Larsson syndrome XR * X-linked ichthyosis Ungrouped * Ichthyosis bullosa of Siemens * Ichthyosis follicularis * Ichthyosis prematurity syndrome * Ichthyosis–sclerosing cholangitis syndrome * Nonbullous congenital ichthyosiform erythroderma * Ichthyosis linearis circumflexa * Ichthyosis hystrix EB and related * EBS * EBS-K * EBS-WC * EBS-DM * EBS-OG * EBS-MD * EBS-MP * JEB * JEB-H * Mitis * Generalized atrophic * JEB-PA * DEB * DDEB * RDEB * related: Costello syndrome * Kindler syndrome * Laryngoonychocutaneous syndrome * Skin fragility syndrome Ectodermal dysplasia * Naegeli syndrome/Dermatopathia pigmentosa reticularis * Hay–Wells syndrome * Hypohidrotic ectodermal dysplasia * Focal dermal hypoplasia * Ellis–van Creveld syndrome * Rapp–Hodgkin syndrome/Hay–Wells syndrome Elastic/Connective * Ehlers–Danlos syndromes * Cutis laxa (Gerodermia osteodysplastica) * Popliteal pterygium syndrome * Pseudoxanthoma elasticum * Van der Woude syndrome Hyperkeratosis/ keratinopathy PPK * diffuse: Diffuse epidermolytic palmoplantar keratoderma * Diffuse nonepidermolytic palmoplantar keratoderma * Palmoplantar keratoderma of Sybert * Meleda disease * syndromic * connexin * Bart–Pumphrey syndrome * Clouston's hidrotic ectodermal dysplasia * Vohwinkel syndrome * Corneodermatoosseous syndrome * plakoglobin * Naxos syndrome * Scleroatrophic syndrome of Huriez * Olmsted syndrome * Cathepsin C * Papillon–Lefèvre syndrome * Haim–Munk syndrome * Camisa disease * focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis * Focal palmoplantar and gingival keratosis * Howel–Evans syndrome * Pachyonychia congenita * Pachyonychia congenita type I * Pachyonychia congenita type II * Striate palmoplantar keratoderma * Tyrosinemia type II * punctate: Acrokeratoelastoidosis of Costa * Focal acral hyperkeratosis * Keratosis punctata palmaris et plantaris * Keratosis punctata of the palmar creases * Schöpf–Schulz–Passarge syndrome * Porokeratosis plantaris discreta * Spiny keratoderma * ungrouped: Palmoplantar keratoderma and spastic paraplegia * desmoplakin * Carvajal syndrome * connexin * Erythrokeratodermia variabilis * HID/KID Other * Meleda disease * Keratosis pilaris * ATP2A2 * Darier's disease * Dyskeratosis congenita * Lelis syndrome * Dyskeratosis congenita * Keratolytic winter erythema * Keratosis follicularis spinulosa decalvans * Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome * Keratosis pilaris atrophicans faciei * Keratosis pilaris Other * cadherin * EEM syndrome * immune system * Hereditary lymphedema * Mastocytosis/Urticaria pigmentosa * Hailey–Hailey see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder Developmental anomalies Midline * Dermoid cyst * Encephalocele * Nasal glioma * PHACE association * Sinus pericranii Nevus * Capillary hemangioma * Port-wine stain * Nevus flammeus nuchae Other/ungrouped * Aplasia cutis congenita * Amniotic band syndrome * Branchial cyst * Cavernous venous malformation * Accessory nail of the fifth toe * Bronchogenic cyst * Congenital cartilaginous rest of the neck * Congenital hypertrophy of the lateral fold of the hallux * Congenital lip pit * Congenital malformations of the dermatoglyphs * Congenital preauricular fistula * Congenital smooth muscle hamartoma * Cystic lymphatic malformation * Median raphe cyst * Melanotic neuroectodermal tumor of infancy * Mongolian spot * Nasolacrimal duct cyst * Omphalomesenteric duct cyst * Poland anomaly * Rapidly involuting congenital hemangioma * Rosenthal–Kloepfer syndrome * Skin dimple * Superficial lymphatic malformation * Thyroglossal duct cyst * Verrucous vascular malformation * Birthmark *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

EEM syndrome

c1857041

wikipedia

https://en.wikipedia.org/wiki/EEM_syndrome

{"gard": ["2078"], "mesh": ["C536190"], "umls": ["C1857041"], "icd-9": ["757.31"], "icd-10": ["Q82.4"], "orphanet": ["1897"], "wikidata": ["Q5322931"]}

Preeclampsia is a hypertensive disorder of pregnancy that is characterized by new-onset hypertension with proteinuria presenting after 20 weeks of gestation, and depending on mild or severe forms may initially present with severe headache, visual disturbances, and hyperreflexia. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Preeclampsia

c0032914

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=275555

{"mesh": ["D011225"], "omim": ["189800", "609402", "609403", "609404", "614595"], "umls": ["C0032914"], "icd-10": ["O14.0", "O14.1", "O14.2", "O14.9"]}

A number sign (#) is used with this entry because of evidence that extraoral halitosis due to methanethiol oxidase deficiency (EHMTO) is caused by homozygous or compound heterozygous mutations in the SELENBP1 gene (604188) on chromosome 1q21. Clinical Features Pol et al. (2018) identified 4 patients from 3 families with a cabbage-like breath odor that brought them to medical attention. All patients were found to have high levels of methanethiol and dimethylsulfide as the main malodorous compounds in their breath. The patients also showed elevated urinary excretion of dimethylsulfoxide and high levels of dimethylsulfide, dimethylsulfoxide, and dimethylsulfone in blood, cerebrospinal fluid (CSF), and urine. Family A was a consanguineous German family of Turkish origin with 2 affected children. The affected female (AII-2) had an uneventful medical history and was the mother of 2 healthy children without malodor. Her brother (AII-3) had cauliflower/cabbage-like bad breath noted since birth that resulted in major contact problems from kindergarten and was more pronounced when fever was present. He also had developmental delay and development of a cerebral motor disorder in childhood, complicated pneumonia, and a marfanoid appearance. At 28 years of age he worked as a machine operator and was married. Both sibs had dimethylsulfone in urine organic acids. Family B was a consanguineous Portuguese family with 1 affected child (BII-2) who came to medical attention at the age of 12 due to cabbage-like breath odor. Urine and sweat had no particular odor. Mild developmental delay was present as well as mild dysmorphia including pectus carinatum and scoliosis. His father had died at the age of 38 from ALS. At age 15 years the patient developed a rapidly progressive weakness of the legs evolving to a general weakness and muscular atrophy with twitching and cramping of muscles. Severely progressive ALS was diagnosed and he died at 16.5 years. Screening for mutations in the SOD1 gene (147450) was negative. Family C was a nonconsanguineous Dutch family with 2 affected sibs. The girl (CII-1) had normal intelligence and her halitosis first became obvious in her student period. The cabbage odor-like smell was worse with drinking beer. She was diagnosed as having extraoral halitosis due to increased dimethylsulfide concentration in her breath. At the age of 36 years she was in good health, but had bilateral ptosis. Family investigations revealed that her healthy brother (CII-2) had increased dimethylsulfide in plasma and breath. Molecular Genetics Pol et al. (2018) identified 4 different pathogenic variants in the SELENBP1 gene in 3 families with autosomal recessive extraoral halitosis. Sibs from a family of Turkish origin were homozygous for a nonsense mutation (604188.0001); a Portuguese patient was homozygous for a splice site mutation (604188.0002); and Dutch sibs carried compound heterozygous missense mutations (604188.0003, 604188.0004). In addition to mutation in SELENBP1, the affected male in the Turkish family carried homozygous premature termination mutations in the OR4S2 and THAP4 (612533) genes; Pol et al. (2018) considered mutation in THAP4 possibly responsible for the broader neurologic phenotype in this patient. Population Genetics Using data from the ExAC database and 15,000 local exomes, Pol et al. (2018) calculated a likely frequency of biallelic pathogenic mutations in the SELENBP1 gene of 1 in 89,306, for a carrier frequency of approximately 1 in 300 individuals. Repeated analysis using in-house exomes found an estimated frequency of 1 in 79,948 for biallelic mutations in SELENBP1. With the frequency of extraoral halitosis estimated at 0.25 to 1.5%, Pol et al. (2018) noted that bilallelic mutation in SELENBP1 may explain a minority of cases. Animal Model Pol et al. (2018) compared Selenbp1 knockout mice with wildtype mice. Selenbp1 knockout mice had no apparent phenotypic changes. MTO activity in erythrocytes of wildtype mice was comparable to that in human erythrocytes and was was strictly dependent on oxygen and yielded stoichiometric amounts of sulfide. MTO activity in knockout mice was deficient, and in heterozygote mice was intermediate. Highest activity in wildtype mice was found in liver, with activity in liver and kidney more than 10-fold higher than that in muscle and brain. Residual activity in knockout mice was less than 6% of that in wildtype animals, demonstrating MTO enzyme deficiency. The DMS levels in plasma of knockout mice were significantly higher than control levels, and DMS levels were also moderately elevated in plasma of heterozygous mice. An accumulation of dimethylsulfone was observed in the plasma of knockout mice but was not detectable in plasma from either wildtype or heterozygous mice. Pol et al. (2018) concluded that overall, the biochemical characteristics of MTO-deficient patients were mimicked in the Selenbp1 knockout mouse model. INHERITANCE \- Autosomal recessive HEAD & NECK Mouth \- Halitosis, extraoral LABORATORY ABNORMALITIES \- Elevated methanethiol and dimethylsulfide (DMS) in breath \- Elevated DMS, DMSO, and DMSO(2) in blood, CSF, and urine MOLECULAR BASIS \- Caused by mutation in the selenium-binding protein 1 gene (SELENBP1, 604188.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

EXTRAORAL HALITOSIS DUE TO METHANETHIOL OXIDASE DEFICIENCY

None

omim

https://www.omim.org/entry/618148

{"omim": ["618148"], "synonyms": ["Alternative titles", "METHANETHIOL OXIDASE DEFICIENCY", "MTO DEFICIENCY", "EXTRAORAL HALITOSIS WITH DIMETHYLSULFOXIDURIA"]}

Autoimmune myocarditis is an autoimmune disease that affects the heart. The condition is characterized by inflammation of the heart muscle (myocardium). Some people with autoimmune myocarditis have no noticeable symptoms of the condition. When present, signs and symptoms may include chest pain, abnormal heartbeat, shortness of breath, fatigue, signs of infection (i.e. fever, headache, sore throat, diarrhea), and leg swelling. The exact underlying cause of the condition is currently unknown; however, autoimmune conditions, in general, occur when the immune system mistakenly attacks healthy tissue. Treatment is based on the signs and symptoms present in each person. In some cases, medications that suppress the immune system may be recommended. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Autoimmune myocarditis

c1608389

gard

https://rarediseases.info.nih.gov/diseases/9519/autoimmune-myocarditis

{"umls": ["C1608389"], "synonyms": []}

Byers et al. (1978) studied a family in which 4 members of 3 generations had spondyloepiphyseal dysplasia (SED) and a punctate dystrophy of the full depth of the corneal stroma. The corneal dystrophy did not interfere with vision. The pedigree pattern was consistent with autosomal dominant inheritance but no male-to-male transmission was noted. The x-ray changes were different from those of X-linked SED (313400). By electron microscopy, marked disorganization of dermal collagen fibrils was demonstrated. The authors suggested a defect in a noncollagenous component of connective tissue that affects collagen fibril formation. Skel \- Spondyloepiphyseal dysplasia (SED) Eyes \- Punctate corneal dystrophy \- No loss of vision Lab \- Marked disorganization of dermal collagen fibrils by EM Inheritance \- Autosomal dominant ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

SPONDYLOEPIPHYSEAL DYSPLASIA WITH PUNCTATE CORNEAL DYSTROPHY

c1866727

omim

https://www.omim.org/entry/183850

{"mesh": ["C566660"], "omim": ["183850"], "orphanet": ["163673"]}

Form of arthritis caused by degeneration of joints Osteoarthritis Other namesDegenerative arthritis, degenerative joint disease, osteoarthrosis The formation of hard knobs at the middle finger joints (known as Bouchard's nodes) and at the farthest joints of the fingers (known as Heberden's nodes) are a common feature of osteoarthritis in the hands. Pronunciation * /ˌɒstioʊɑːrˈθraɪtɪs/ SpecialtyRheumatology, orthopedics SymptomsJoint pain, stiffness, joint swelling, decreased range of motion[1] Usual onsetOver years[1] CausesConnective tissue disease, previous joint injury, abnormal joint or limb development, inherited factors[1][2] Risk factorsOverweight, legs of different lengths, job with high levels of joint stress[1][2] Diagnostic methodBased on symptoms, supported by other testing[1] TreatmentExercise, efforts to decrease joint stress, support groups, pain medications, joint replacement[1][2][3] Frequency237 million / 3.3% (2015)[4] Osteoarthritis (OA) is a type of joint disease that results from breakdown of joint cartilage and underlying bone.[5] The most common symptoms are joint pain and stiffness.[1] Usually the symptoms progress slowly over years.[1] Initially they may occur only after exercise but can become constant over time.[1] Other symptoms may include joint swelling, decreased range of motion, and, when the back is affected, weakness or numbness of the arms and legs.[1] The most commonly involved joints are the two near the ends of the fingers and the joint at the base of the thumbs; the knee and hip joints; and the joints of the neck and lower back.[1] Joints on one side of the body are often more affected than those on the other.[1] The symptoms can interfere with work and normal daily activities.[1] Unlike some other types of arthritis, only the joints, not internal organs, are affected.[1] Causes include previous joint injury, abnormal joint or limb development, and inherited factors.[1][2] Risk is greater in those who are overweight, have legs of different lengths, or have jobs that result in high levels of joint stress.[1][2][6] Osteoarthritis is believed to be caused by mechanical stress on the joint and low grade inflammatory processes.[7] It develops as cartilage is lost and the underlying bone becomes affected.[1] As pain may make it difficult to exercise, muscle loss may occur.[2][8] Diagnosis is typically based on signs and symptoms, with medical imaging and other tests used to support or rule out other problems.[1] In contrast to rheumatoid arthritis, in osteoarthritis the joints do not become hot or red.[1] Treatment includes exercise, decreasing joint stress such as by rest or use of a cane, support groups, and pain medications.[1][3] Weight loss may help in those who are overweight.[1] Pain medications may include paracetamol (acetaminophen) as well as NSAIDs such as naproxen or ibuprofen.[1] Long-term opioid use is not recommended due to lack of information on benefits as well as risks of addiction and other side effects.[1][3] Joint replacement surgery may be an option if there is ongoing disability despite other treatments.[2] An artificial joint typically lasts 10 to 15 years.[9] Osteoarthritis is the most common form of arthritis, affecting about 237 million people, or 3.3% of the world's population.[4][10] In the United States, 30 to 53 million people are affected,[11][12] and in Australia, about 1.9 million people are affected.[13] It becomes more common as people become older.[1] Among those over 60 years old, about 10% of males and 18% of females are affected.[2] Osteoarthritis is the cause of about 2% of years lived with disability.[10] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Primary * 2.1.1 Occupational * 2.2 Secondary * 3 Pathophysiology * 4 Diagnosis * 4.1 Classification * 5 Management * 5.1 Lifestyle changes * 5.2 Physical measures * 5.3 Medication * 5.3.1 By mouth * 5.3.2 Topical * 5.3.3 Joint injections * 5.3.3.1 Steroids * 5.3.3.2 Hyaluronic acid * 5.3.3.3 Platelet rich plasma * 5.4 Surgery * 5.4.1 Bone fusion * 5.4.2 Joint replacement * 5.4.3 Other surgical options * 5.5 Alternative medicine * 5.5.1 Glucosamine and chondroitin * 5.5.2 Other remedies * 5.5.3 Acupuncture and other interventions * 6 Epidemiology * 7 History * 7.1 Etymology * 8 Other animals * 9 Research * 9.1 Therapies * 9.2 Cause * 9.3 Diagnostic biomarkers * 10 References * 11 External links ## Signs and symptoms[edit] Osteoarthritis most often occurs in the hands (at the ends of the fingers and thumbs), neck, lower back, knees, and hips. The main symptom is pain, causing loss of ability and often stiffness. The pain is typically made worse by prolonged activity and relieved by rest. Stiffness is most common in the morning, and typically lasts less than thirty minutes after beginning daily activities, but may return after periods of inactivity. Osteoarthritis can cause a crackling noise (called "crepitus") when the affected joint is moved, especially shoulder and knee joint. A person may also complain of joint locking and joint instability. These symptoms would affect their daily activities due to pain and stiffness.[14] Some people report increased pain associated with cold temperature, high humidity, or a drop in barometric pressure, but studies have had mixed results.[15] Osteoarthritis commonly affects the hands, feet, spine, and the large weight-bearing joints, such as the hips and knees, although in theory, any joint in the body can be affected. As osteoarthritis progresses, movement patterns (such as gait), are typically affected.[1] Osteoarthritis is the most common cause of a joint effusion of the knee.[16] In smaller joints, such as at the fingers, hard bony enlargements, called Heberden's nodes (on the distal interphalangeal joints) or Bouchard's nodes (on the proximal interphalangeal joints), may form, and though they are not necessarily painful, they do limit the movement of the fingers significantly. Osteoarthritis of the toes may be a factor causing formation of bunions,[17] rendering them red or swollen. ## Causes[edit] Damage from mechanical stress with insufficient self repair by joints is believed to be the primary cause of osteoarthritis.[18] Sources of this stress may include misalignments of bones caused by congenital or pathogenic causes; mechanical injury; excess body weight; loss of strength in the muscles supporting a joint; and impairment of peripheral nerves, leading to sudden or uncoordinated movements.[18] However exercise, including running in the absence of injury, has not been found to increase the risk of knee osteoarthritis.[19] Nor has cracking one's knuckles been found to play a role.[20] ### Primary[edit] The development of osteoarthritis is correlated with a history of previous joint injury and with obesity, especially with respect to knees.[21] Changes in sex hormone levels may play a role in the development of osteoarthritis, as it is more prevalent among post-menopausal women than among men of the same age.[1][22] Conflicting evidence exists for the differences in hip and knee osteoarthritis in African American and Caucasians.[23] #### Occupational[edit] See also: Occupational disease and Occupational injury Increased risk of developing knee and hip osteoarthritis was found among those who work with manual handling (e.g. lifting), have physically demanding work, walk at work, and have climbing tasks at work (e.g. climb stairs or ladders).[6] With hip osteoarthritis in particular, increased risk of development over time was found among those who work in bent or twisted positions.[6] For knee osteoarthritis in particular, increased risk was found among those who work in a kneeling or squatting position, experience heavy lifting in combination with a kneeling or squatting posture, and work standing up.[6] Women and men have similar occupational risks for the development of osteoarthritis.[6] ### Secondary[edit] Lateral Frontal Secondary osteoarthritis of the ankle (due to an old bone fracture) in an 82-year-old woman This type of osteoarthritis is caused by other factors but the resulting pathology is the same as for primary osteoarthritis: * Alkaptonuria * Congenital disorders of joints * Diabetes doubles the risk of having a joint replacement due to osteoarthritis and people with diabetes have joint replacements at a younger age than those without diabetes.[24] * Ehlers-Danlos syndrome * Hemochromatosis and Wilson's disease * Inflammatory diseases (such as Perthes' disease), (Lyme disease), and all chronic forms of arthritis (e.g., costochondritis, gout, and rheumatoid arthritis). In gout, uric acid crystals cause the cartilage to degenerate at a faster pace. * Injury to joints or ligaments (such as the ACL), as a result of an accident or orthopedic operations. * Ligamentous deterioration or instability may be a factor. * Marfan syndrome * Obesity * Joint infection ## Pathophysiology[edit] Healthy hip joint Hip joint with osteoarthritis[25] While osteoarthritis is a degenerative joint disease that may cause gross cartilage loss and morphological damage to other joint tissues, more subtle biochemical changes occur in the earliest stages of osteoarthritis progression. The water content of healthy cartilage is finely balanced by compressive force driving water out and hydrostatic and osmotic pressure drawing water in.[26][27] Collagen fibres exert the compressive force, whereas the Gibbs–Donnan effect and cartilage proteoglycans create osmotic pressure which tends to draw water in.[27] However, during onset of osteoarthritis, the collagen matrix becomes more disorganized and there is a decrease in proteoglycan content within cartilage. The breakdown of collagen fibers results in a net increase in water content.[28][29][30][31][32] This increase occurs because whilst there is an overall loss of proteoglycans (and thus a decreased osmotic pull),[29][33] it is outweighed by a loss of collagen.[27][33] Without the protective effects of the proteoglycans, the collagen fibers of the cartilage can become susceptible to degradation and thus exacerbate the degeneration. Inflammation of the synovium (joint cavity lining) and the surrounding joint capsule can also occur, though often mild (compared to the synovial inflammation that occurs in rheumatoid arthritis). This can happen as breakdown products from the cartilage are released into the synovial space, and the cells lining the joint attempt to remove them.[citation needed] Other structures within the joint can also be affected.[34] The ligaments within the joint become thickened and fibrotic and the menisci can become damaged and wear away.[35] Menisci can be completely absent by the time a person undergoes a joint replacement. New bone outgrowths, called "spurs" or osteophytes, can form on the margins of the joints, possibly in an attempt to improve the congruence of the articular cartilage surfaces in the absence of the menisci. The subchondral bone volume increases and becomes less mineralized (hypomineralization).[36] All these changes can cause problems functioning. The pain in an osteoarthritic joint has been related to thickened synovium[37] and to subchondral bone lesions.[38] ## Diagnosis[edit] Synovial fluid examination[39][40] Type WBC per mm3 % neutrophils Viscosity Appearance Normal <200 0 High Transparent Osteoarthritis <5000 <25 High Clear yellow Trauma <10,000 <50 Variable Bloody Inflammatory 2,000-50,000 50-80 Low Cloudy yellow Septic arthritis >50,000 >75 Low Cloudy yellow Gonorrhea ~10,000 60 Low Cloudy yellow Tuberculosis ~20,000 70 Low Cloudy yellow Inflammatory = gout, rheumatoid arthritis, rheumatic fever Diagnosis is made with reasonable certainty based on history and clinical examination.[41][42] X-rays may confirm the diagnosis. The typical changes seen on X-ray include: joint space narrowing, subchondral sclerosis (increased bone formation around the joint), subchondral cyst formation, and osteophytes.[43] Plain films may not correlate with the findings on physical examination or with the degree of pain.[44] Usually other imaging techniques are not necessary to clinically diagnose osteoarthritis. In 1990, the American College of Rheumatology, using data from a multi-center study, developed a set of criteria for the diagnosis of hand osteoarthritis based on hard tissue enlargement and swelling of certain joints.[45] These criteria were found to be 92% sensitive and 98% specific for hand osteoarthritis versus other entities such as rheumatoid arthritis and spondyloarthropathies.[46] * Severe osteoarthritis and osteopenia of the carpal joint and 1st carpometacarpal joint. * MRI of osteoarthritis in the knee, with characteristic narrowing of the joint space. * Primary osteoarthritis of the left knee. Note the osteophytes, narrowing of the joint space (arrow), and increased subchondral bone density (arrow). * Damaged cartilage from sows. (a) cartilage erosion (b)cartilage ulceration (c)cartilage repair (d)osteophyte (bone spur) formation. * Histopathology of osteoarthrosis of a knee joint in an elderly female. * Histopathology of osteoarthrosis of a knee joint in an elderly female. * In a healthy joint, the ends of bones are encased in smooth cartilage. Together, they are protected by a joint capsule lined with a synovial membrane that produces synovial fluid. The capsule and fluid protect the cartilage, muscles, and connective tissues. * With osteoarthritis, the cartilage becomes worn away. Spurs grow out from the edge of the bone, and synovial fluid increases. Altogether, the joint feels stiff and sore. * Osteoarthritis * Bone (left) and clinical (right) changes of the hand in osteoarthritis ### Classification[edit] Further information: Radiographic classification of osteoarthritis A number of classification systems are used for gradation of osteoarthritis: * WOMAC scale, taking into account pain, stiffness and functional limitation.[47] * Kellgren-Lawrence grading scale for osteoarthritis of the knee. It uses only projectional radiography features. * Tönnis classification for osteoarthritis of the hip joint, also using only projectional radiography features.[48] * Knee injury and Osteoarthritis Outcome Score (KOOS) and Hip disability and Osteoarthritis Outcome Score (HOOS) surveys.[49][50] Osteoarthritis can be classified into either primary or secondary depending on whether or not there is an identifiable underlying cause. X-ray of erosive osteoarthritis of the fingers, also zooming in on two joints with the typical "gull-wing" appearance. Both primary generalized nodal osteoarthritis and erosive osteoarthritis (EOA, also called inflammatory osteoarthritis) are sub-sets of primary osteoarthritis. EOA is a much less common, and more aggressive inflammatory form of osteoarthritis which often affects the distal interphalangeal joints of the hand and has characteristic articular erosive changes on x-ray.[51] Osteoarthritis can be classified by the joint affected: * Hand: * Trapeziometacarpal osteoarthritis * Wrist (wrist osteoarthritis) * Vertebral column (spondylosis) * Facet joint arthrosis * Hip osteoarthritis * Knee osteoarthritis ## Management[edit] Some kinds of exercise recommended in OA. Lifestyle modification (such as weight loss and exercise) and pain medications are the mainstays of treatment. Acetaminophen (also known as paracetamol) is recommended first line with NSAIDs being used as add on therapy only if pain relief is not sufficient.[52][53] Medications that alter the course of the disease have not been found as of 2018.[54] Recommendations include modification of risk factors through targeted interventions including 1) obesity and overweight, 2) physical activity, 3) dietary exposures, 4) comorbidity, 5) biomechanical factors, 6) occupational factors.[55] ### Lifestyle changes[edit] For overweight people, weight loss may be an important factor.[56] Patient education has been shown to be helpful in the self-management of arthritis.[56] It decreases pain, improves function, reduces stiffness and fatigue, and reduces medical usage.[56] Patient education can provide on average 20% more pain relief when compared to NSAIDs alone.[56] ### Physical measures[edit] Moderate exercise may be beneficial with respect to pain and function in those with osteoarthritis of the knee and hip.[57][58][59] These exercises should occur at least three times per week.[60] While some evidence supports certain physical therapies, evidence for a combined program is limited.[61] Providing clear advice, making exercises enjoyable, and reassuring people about the importance of doing exercises may lead to greater benefit and more participation.[59] Limited evidence suggests that supervised exercise therapy may improve exercise adherence.[62] There is not enough evidence to determine the effectiveness of massage therapy.[63] The evidence for manual therapy is inconclusive.[64] Functional, gait, and balance training have been recommended to address impairments of position sense, balance, and strength in individuals with lower extremity arthritis as these can contribute to a higher rate of falls in older individuals.[65][66] For people with hand osteoarthritis, exercises may provide small benefits for improving hand function, reducing pain, and relieving finger joint stiffness.[67] Lateral wedge insoles and neutral insoles do not appear to be useful in osteoarthritis of the knee.[68][69][70] Knee braces may help[71] but their usefulness has also been disputed.[70] For pain management heat can be used to relieve stiffness, and cold can relieve muscle spasms and pain.[72] Among people with hip and knee osteoarthritis, exercise in water may reduce pain and disability, and increase quality of life in the short term.[73] Also therapeutic exercise programs such as aerobics and walking reduce pain and improve physical functioning for up to 6 months after the end of the program for people with knee osteoarthritis.[74] ### Medication[edit] Treatment recommendations by risk factors GI risk CVD risk Option Low Low NSAID, or paracetamol[75] Moderate Low Paracetamol, or low dose NSAID with antacid[75] Low Moderate Paracetamol, or low dose aspirin with an antacid[75] Moderate Moderate Low dose paracetamol, aspirin, and antacid. Monitoring for abdominal pain or black stool.[75] #### By mouth[edit] The pain medication paracetamol (acetaminophen) is the first line treatment for osteoarthritis.[52][76] Pain relief does not differ according to dosage.[53] However, a 2015 review found acetaminophen to have only a small short term benefit with some laboratory concerns of liver inflammation.[77] For mild to moderate symptoms effectiveness of acetaminophen is similar to non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen, though for more severe symptoms NSAIDs may be more effective.[52] NSAIDs are associated with greater side effects such as gastrointestinal bleeding.[52] Another class of NSAIDs, COX-2 selective inhibitors (such as celecoxib) are equally effective when compared to nonselective NSAIDs, and have lower rates of adverse gastrointestinal effects, but higher rates of cardiovascular disease such as myocardial infarction.[78] They are also more expensive than non-specific NSAIDs.[79] Benefits and risks vary in individuals and need consideration when making treatment decisions,[80] and further unbiased research comparing NSAIDS and COX-2 selective inhibitors is needed.[81] NSAIDS applied topically are effective for a small number of people.[82] The COX-2 selective inhibitor rofecoxib was removed from the market in 2004, as cardiovascular events were associated with long term use.[83] Failure to achieve desired pain relief in osteoarthritis after 2 weeks should trigger reassessment of dosage and pain medication.[84] Opioids by mouth, including both weak opioids such as tramadol and stronger opioids, are also often prescribed. Their appropriateness is uncertain, and opioids are often recommended only when first line therapies have failed or are contraindicated.[3][85] This is due to their small benefit and relatively large risk of side effects.[86][87] The use of tramadol likely does not improve pain or physical function and likely increases the incidence of adverse side effects.[87] Oral steroids are not recommended in the treatment of osteoarthritis.[76] Use of the antibiotic doxycycline orally for treating osteoarthritis is not associated with clinical improvements in function or joint pain.[88] Any small benefit related to the potential for doxycycline therapy to address the narrowing of the joint space is not clear, and any benefit is outweighed by the potential harm from side effects.[88] #### Topical[edit] There are several NSAIDs available for topical use, including diclofenac. A Cochrane review from 2016 concluded that reasonably reliable evidence is available only for use of topical diclofenac and ketoprofen in people aged over 40 years with painful knee arthritis.[82] Transdermal opioid pain medications are not typically recommended in the treatment of osteoarthritis.[86] The use of topical capsaicin to treat osteoarthritis is controversial, as some reviews found benefit[89][90] while others did not.[91] #### Joint injections[edit] Ultrasound-guided hip joint injection: A skin mark is made to mark the optimal point of entry for the needle.[92] ##### Steroids[edit] Joint injection of glucocorticoids (such as hydrocortisone) leads to short term pain relief that may last between a few weeks and a few months.[93] A 2015 Cochrane review found that intra-articular corticosteroid injections of the knee did not benefit quality of life and had no effect on knee joint space; clinical effects one to six weeks after injection could not be determined clearly due to poor study quality.[94] Another 2015 study reported negative effects of intra-articular corticosteroid injections at higher doses,[95] and a 2017 trial showed reduction in cartilage thickness with intra-articular triamcinolone every 12 weeks for 2 years compared to placebo.[96] A 2018 study found that intra-articular triamcinolone is associated with an increase in intraocular pressure.[97] ##### Hyaluronic acid[edit] Injections of hyaluronic acid have not produced improvement compared to placebo for knee arthritis,[98][99] but did increase risk of further pain.[98] In ankle osteoarthritis, evidence is unclear.[100] ##### Platelet rich plasma[edit] The effectiveness of injections of platelet-rich plasma is unclear; there are suggestions that such injections improve function but not pain, and are associated with increased risk.[vague][101][102] A Cochrane review of studies involving PRP found the evidence to be insufficient.[103] ### Surgery[edit] #### Bone fusion[edit] Arthrodesis (fusion) of the bones may be an option in some types of osteoarthritis. An example is ankle osteoarthritis, in which ankle fusion is considered to be the gold standard treatment in end-stage cases.[104] #### Joint replacement[edit] If the impact of symptoms of osteoarthritis on quality of life is significant and more conservative management is ineffective, joint replacement surgery or resurfacing may be recommended. Evidence supports joint replacement for both knees and hips as it is both clinically effective[105][106] and cost-effective.[107][108] For people who have shoulder osteoarthritis and do not respond to medications, surgical options include a shoulder hemiarthroplasty (replacing a part of the joint), and total shoulder arthroplasty (replacing the joint).[109] Biological joint replacement involves replacing the diseased tissues with new ones. This can either be from the person (autograft) or from a donor (allograft).[110] People undergoing a joint transplant (osteochondral allograft) do not need to take immunosuppressants as bone and cartilage tissues have limited immune responses.[111] Autologous articular cartilage transfer from a non-weight-bearing area to the damaged area, called osteochondral autograft transfer system (OATS), is one possible procedure that is being studied.[112] When the missing cartilage is a focal defect, autologous chondrocyte implantation is also an option.[113] #### Other surgical options[edit] Osteotomy may be useful in people with knee osteoarthritis, but has not been well studied and it is unclear whether it is more effective than non-surgical treatments or other types of surgery.[114][115] Arthroscopic surgery is largely not recommended, as it does not improve outcomes in knee osteoarthritis,[116][117] and may result in harm.[118] It is unclear whether surgery is beneficial in people with mild to moderate knee osteoarthritis.[115] ### Alternative medicine[edit] #### Glucosamine and chondroitin[edit] The effectiveness of glucosamine is controversial.[119] Reviews have found it to be equal to[120][121] or slightly better than placebo.[122][123] A difference may exist between glucosamine sulfate and glucosamine hydrochloride, with glucosamine sulfate showing a benefit and glucosamine hydrochloride not.[124] The evidence for glucosamine sulfate having an effect on osteoarthritis progression is somewhat unclear and if present likely modest.[125] The Osteoarthritis Research Society International recommends that glucosamine be discontinued if no effect is observed after six months[126] and the National Institute for Health and Care Excellence no longer recommends its use.[8] Despite the difficulty in determining the efficacy of glucosamine, it remains a viable treatment option.[127] The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommends glucosamine sulfate and chondroitin sulfate for knee osteoarthritis.[128] Its use as a therapy for osteoarthritis is usually safe.[127][129] A 2015 Cochrane review of clinical trials of chondroitin found that most were of low quality, but that there was some evidence of short-term improvement in pain and few side effects; it does not appear to improve or maintain the health of affected joints.[130] #### Other remedies[edit] Avocado–soybean unsaponifiables (ASU) is an extract made from avocado oil and soybean oil[131] that is sold under many brand names worldwide as a dietary supplement[132] and as a drug in France.[133] A 2014 Cochrane review found that while ASU might help relieve pain in the short term for some people with osteoarthritis, it does not appear to improve or maintain the health of affected joints. The review noted a high-quality two-year clinical trial comparing ASU to chondroitin, which has uncertain efficacy in osteoarthritis; the study found no difference between the two.[131] The review also found that although ASU appears to be safe, it has not been adequately studied for its safety to be determined.[131] A few high-quality studies of Boswellia serrata show consistent, but small, improvements in pain and function.[131] Curcumin,[134] phytodolor,[89] and s-adenosyl methionine (SAMe)[89][63] may be effective in improving pain. A 2009 Cochrane review recommended against the routine use of SAMe as there have not been sufficient high-quality trials performed to evaluate its effect.[135] There is tentative evidence to support hyaluronan,[136] methylsulfonylmethane (MSM),[89] and rose hip.[89] There is little evidence supporting benefits for some supplements, including: the Ayurvedic herbal preparations with brand names Articulin F and Eazmov; Duhuo Jisheng Wan, a Chinese herbal preparation; fish liver oil; ginger; russian olive; the herbal preparation gitadyl; omega-3 fatty acids; the brand-name product Reumalax; stinging nettle; vitamins A, C, and E in combination; vitamin E alone; vitamin K; vitamin D; collagen; and willow bark. There is insufficient evidence to make a recommendation about the safety and efficacy of these treatments.[89][137] #### Acupuncture and other interventions[edit] While acupuncture leads to improvements in pain relief, this improvement is small and may be of questionable importance.[138] Waiting list–controlled trials for peripheral joint osteoarthritis do show clinically relevant benefits, but these may be due to placebo effects.[139][140] Acupuncture does not seem to produce long-term benefits.[141] Electrostimulation techniques such as TENS have been used for twenty years to treat osteoarthritis in the knee, however there is no conclusive evidence to show that it reduces pain or disability.[142] A Cochrane review of low-level laser therapy found unclear evidence of benefit,[143] whereas another review found short-term pain relief for osteoarthritic knees.[144] Further research is needed to determine if balnotherapy for osteoarthritis (mineral baths or spa treatments) improves a person's quality of life or ability to function.[145] The use of ice or cold packs may be beneficial; however, further research is needed.[146] There is no evidence of benefit from placing hot packs on joints.[146] There is low quality evidence that therapeutic ultrasound may be beneficial for people with osteoarthritis of the knee; however, further research is needed to confirm and determine the degree and significance of this potential benefit.[147] There is weak evidence suggesting that electromagnetic field treatment may result in moderate pain relief; however, further research is necessary and it is not known if electromagnetic field treatment can improve quality of life or function.[148] Viscosupplementation for osteoarthritis of the knee may have positive effects on pain and function at 5 to 13 weeks post-injection.[149] ## Epidemiology[edit] Disability-adjusted life year for osteoarthritis per 100,000 inhabitants in 2004.[150] no data ≤ 200 200–220 220–240 240–260 260–280 280–300 300–320 320–340 340–360 360–380 380–400 ≥ 400 Globally, as of 2010[update], approximately 250 million people had osteoarthritis of the knee (3.6% of the population).[151][152] Hip osteoarthritis affects about 0.85% of the population.[151] As of 2004[update], osteoarthritis globally causes moderate to severe disability in 43.4 million people.[153] Together, knee and hip osteoarthritis had a ranking for disability globally of 11th among 291 disease conditions assessed.[151] As of 2012[update], osteoarthritis affected 52.5 million people in the United States, approximately 50% of whom were 65 years or older.[11] It is estimated that 80% of the population have radiographic evidence of osteoarthritis by age 65, although only 60% of those will have symptoms.[154] The rate of osteoarthritis in the United States is forecast to be 78 million (26%) adults by 2040.[11] In the United States, there were approximately 964,000 hospitalizations for osteoarthritis in 2011, a rate of 31 stays per 10,000 population.[155] With an aggregate cost of $14.8 billion ($15,400 per stay), it was the second-most expensive condition seen in U.S. hospital stays in 2011. By payer, it was the second-most costly condition billed to Medicare and private insurance.[156][157] ## History[edit] Evidence for osteoarthritis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. ### Etymology[edit] Osteoarthritis is derived from the prefix osteo- (from Ancient Greek: ὀστέον, romanized: ostéon, lit. 'bone') combined with arthritis (from ἀρθρῖτῐς, arthrîtis, lit. ''of or in the joint''), which is itself derived from arthr- (from ἄρθρον, árthron, lit. ''joint, limb'') and -itis (from -ῖτις, -îtis, lit. ''pertaining to''), the latter suffix having come to be associated with inflammation.[158] The -itis of osteoarthritis could be considered misleading as inflammation is not a conspicuous feature. Some clinicians refer to this condition as osteoarthrosis to signify the lack of inflammatory response,[159] the suffix -osis (from -ωσις, -ōsis, lit. ''(abnormal) state, condition, or action'') simply referring to the pathosis itself. ## Other animals[edit] Osteoarthritis has been reported in fossils of the large carnivorous dinosaur Allosaurus fragilis.[160] ## Research[edit] ### Therapies[edit] See also: Disease-modifying osteoarthritis drug Therapies under investigation include the following: * Strontium ranelate \- may decrease degeneration in osteoarthritis and improve outcomes[161][162] * Gene therapy - Gene transfer strategies aim to target the disease process rather than the symptoms.[163] Cell-mediated gene therapy is also being studied.[164][165] One version was approved in South Korea for the treatment of moderate knee osteoarthritis, but later revoked for the mislabeling and the false reporting of an ingredient used.[166][167] The drug was administered intra-articularly.[167] ### Cause[edit] As well as attempting to find disease-modifying agents for osteoarthritis, there is emerging evidence that a system-based approach is necessary to find the causes of osteoarthritis.[168] ### Diagnostic biomarkers[edit] Guidelines outlining requirements for inclusion of soluble biomarkers in osteoarthritis clinical trials were published in 2015,[169] but as of 2015[update], there are no validated biomarkers for osteoarthritis. A 2015 systematic review of biomarkers for osteoarthritis looking for molecules that could be used for risk assessments found 37 different biochemical markers of bone and cartilage turnover in 25 publications.[170] The strongest evidence was for urinary C-terminal telopeptide of type II collagen (uCTX-II) as a prognostic marker for knee osteoarthritis progression, and serum cartilage oligomeric matrix protein (COMP) levels as a prognostic marker for incidence of both knee and hip osteoarthritis. A review of biomarkers in hip osteoarthritis also found associations with uCTX-II.[171] Procollagen type II C-terminal propeptide (PIICP) levels reflect type II collagen synthesis in body and within joint fluid PIICP levels can be used as a prognostic marker for early osteoarthritis.[172] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z "Osteoarthritis". National Institute of Arthritis and Musculoskeletal and Skin Diseases. April 2015. 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International Journal of Molecular Sciences. 18 (3): 601. doi:10.3390/ijms18030601. PMC 5372617. PMID 28287489. ## External links[edit] Classification D * ICD-10: M15-M19, M47 * ICD-9-CM: 715 * OMIM: 165720 * MeSH: D010003 * DiseasesDB: 9313 * SNOMED CT: 227588009 External resources * MedlinePlus: 000423 * eMedicine: med/1682 orthoped/427 pmr/93 radio/492 * Patient UK: Osteoarthritis Wikimedia Commons has media related to Osteoarthritis. * American College of Rheumatology Factsheet on OA * Kolasinski, SL; Neogi, T; Hochberg, MC; Oatis, C; Guyatt, G; Block, J; Callahan, L; Copenhaver, C; Dodge, C; Felson, D; Gellar, K; Harvey, WF; Hawker, G; Herzig, E; Kwoh, CK; Nelson, AE; Samuels, J; Scanzello, C; White, D; Wise, B; Altman, RD; DiRenzo, D; Fontanarosa, J; Giradi, G; Ishimori, M; Misra, D; Shah, AA; Shmagel, AK; Thoma, LM; Turgunbaev, M; Turner, AS; Reston, J (February 2020). "2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee". Arthritis & Rheumatology. 72 (2): 220–233. doi:10.1002/art.41142. PMID 31908163. * "Osteoarthritis". MedlinePlus. U.S. National Library of Medicine. * v * t * e Diseases of joints General * Arthritis * Monoarthritis * Oligoarthritis * Polyarthritis Symptoms * Joint pain * Joint stiffness Inflammatory Infectious * Septic arthritis * Tuberculosis arthritis Crystal * Chondrocalcinosis * CPPD (Psudogout) * Gout Seronegative * Reactive arthritis * Psoriatic arthritis * Ankylosing spondylitis Other * Juvenile idiopathic arthritis * Rheumatoid arthritis * Felty's syndrome * Palindromic rheumatism * Adult-onset Still's disease Noninflammatory * Hemarthrosis * Osteoarthritis * Heberden's node * Bouchard's nodes * Osteophyte * Medicine portal Authority control * GND: 4143132-7 * LCCN: sh85095960 * NDL: 01203435 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Osteoarthritis

c0029408

wikipedia

https://en.wikipedia.org/wiki/Osteoarthritis

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Partial hydatiform mole is a type of hydatiform mole (see this term) characterized by abnormal hyperplastic trophoblasts and hydropic villi due to fertilization of a normal ovocyte by two spermatozoa or one abnormal spermatozoon (allowing for some fetal development), and that manifests with vaginal bleeding accompanied by nausea and frequent vomiting, hyperemesis gravidarum, hyperthyroidism and risk of spontaneous miscarriage. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Partial hydatidiform mole

c0334529

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254693

{"mesh": ["D006828"], "umls": ["C0334529"], "icd-10": ["O01.1"], "synonyms": ["Incomplete hydatidiform mole", "Incomplete molar pregnancy", "Partial molar pregnancy"]}

Balantidiasis Balantidium coli as seen in a wet mount of a stool specimen. The organism is surrounded by cilia. SpecialtyInfectious disease Balantidiasis is a protozoan infection caused by infection with Balantidium coli.[1] ## Contents * 1 Symptoms and signs * 2 Transmission * 3 Morphology * 4 Diagnosis * 5 Prevention * 6 Treatment * 7 History * 8 References * 9 External links ## Symptoms and signs[edit] Usually asymptomatic in immunocompetent individuals, but the symptoms of balantidiasis include: * Intermittent diarrhea * Constipation * Vomiting * Abdominal pain * Anorexia * Weight loss * Headache * Colitis * Marked fluid loss The most common ones are intermittent diarrhea and constipation or inflammation of the colon combined with abdominal cramps and bloody stools. ## Transmission[edit] Balantidium is the only ciliated protozoan known to infect humans. Balantidiasis is a zoonotic disease and is acquired by humans via the feco-oral route from the normal host, the pig, where it is asymptomatic. “Contaminated water is the most common mechanism of transmission. Equally dangerous, however, is the ingestion of contaminated food.” [2] ## Morphology[edit] Balantidium coli exists in either of two developmental stages: trophozoites and cysts.[3] In the trophozoite form, they can be oblong or spherical, and are typically 30 to 150 µm in length and 25 to 120 µm in width.[4] It is its size at this stage that allows Balantidium coli to be characterized as the largest protozoan parasite of humans.[3] Trophozoites possess both a macronucleus and a micronucleus, and both are usually visible.[3] The macronucleus is large and sausage-shaped while the micronucleus is less prominent.[4] At this stage, the organism is not infective but it can replicate by transverse binary fission.[3] In its cyst stage, the parasite takes on a smaller, more spherical shape, with a diameter of around 40 to 60 µm.[4] Unlike the trophozoite, whose surface is covered only with cilia, the cyst form has a tough wall made of one or more layers.[3] The cyst form also differs from the trophozoite form because it is non-motile and does not undergo reproduction.[3] Instead, the cyst is the form that the parasite takes when it causes infection.[3] ## Diagnosis[edit] The diagnosis of balantidiasis can be an intricate process, partly because the related symptoms may or may not be present. However, the diagnosis of balantidiasis can be considered when a patient has diarrhea combined with a probable history of current exposure to pigs (since pigs are the primary reservoir), contact with infected persons, or anal intercourse.[5] In addition, the diagnosis of balantidiasis can be made by microscopic examination of stools in search of trophozoites or cysts,[6] or colonoscopy or sigmoidoscopy to obtain a biopsy from the large intestines which may provide evidence for the presence of trophozoites. ## Prevention[edit] Preventative measures require effective personal and community hygiene. Some specific safeguards include the following:[citation needed] * Purification of drinking water. * Proper handling of food. * Careful disposal of human feces. * Monitoring the contacts of balantidiasis patients. ## Treatment[edit] Balantidiasis can be treated with tetracycline,[7] carbarsone, metronidazole, or diiodohydroxyquin. ## History[edit] A trophozoite of Balantidium coli The first study to generate balantidiasis in humans was undertaken by Cassagrandi and Barnagallo in 1896.[8] However, this experiment was not successful in creating an infection and it was unclear whether Balantidium coli was the actual parasite used.[8] The first case of balantidiasis in the Philippines, where it is the most common, was reported in 1904.[9][4] Currently, Balantidium coli is distributed worldwide but less than 1% of the human population is infected.[10][4] Pigs are a major reservoir of the parasite, and infection of humans occurs more frequently in areas where pigs comingle with people.[10] This includes places like the Philippines, as previously mentioned, but also includes countries such as Bolivia and Papua New Guinea.[10][11] But pigs are not the only animal where the parasite is found. For example, Balantidium coli also has a high rate of incidence in rats.[12] In a Japanese study that analyzed the fecal samples in 56 mammalian species, Balantidium coli was found to be present not just in all the wild boars tested (with wild boars and pigs being considered the same species), it was also found in five species of non human primate: Chimpanzee (Pan troglodytes), White-handed gibbon (Hylobates lar), Squirrelmonkey (Saimiri sciurea), Sacred baboon (Comopithecus hamadryas), and Japanese macaque (Macaca fuscata).[13] In other studies, Balantidium coli was also found in species from the orders Rodentia and Carnivora.[13] ## References[edit] 1. ^ Schuster FL, Ramirez-Avila L (October 2008). "Current World Status of Balantidium coli". Clin. Microbiol. Rev. 21 (4): 626–38. doi:10.1128/CMR.00021-08. PMC 2570149. PMID 18854484. 2. ^ Dwight D., Bowman (December 9, 2013). Georgi's Parasitology For Veterinarians. St. Louis, MO: Elsevier Saunders.: Saunders; 10 edition. 3. ^ a b c d e f g Ramachandran, Ambili. "Morphology." The Parasite: Balantidium coli The Disease: Balantidiasis. 23 May 2003. Stanford University. 16 May 2009 <http://www.stanford.edu/group/parasites/ParaSites2003/Balantidium/Morphology.htm>. 4. ^ a b c d e Roberts, Larry S., and John Janovy Jr. Gerald D. Schmidt & Larry S. Roberts' Foundations of Parasitology. 8th ed. New York: McGraw-Hill, 2009. 5. ^ Ferry T, Bouhour D, De Monbrison F, et al. (May 2004). "Severe peritonitis due to Balantidium coli acquired in France". Eur. J. Clin. Microbiol. Infect. Dis. 23 (5): 393–5. doi:10.1007/s10096-004-1126-4. PMID 15112068. S2CID 20552666. 6. ^ Walzer PD, Judson FN, Murphy KB, Healy GR, English DK, Schultz MG (January 1973). "Balantidiasis outbreak in Truk". Am. J. Trop. Med. Hyg. 22 (1): 33–41. doi:10.4269/ajtmh.1973.22.33. PMID 4684887. 7. ^ "Balantidiasis: Treatment & Medication - eMedicine Infectious Diseases". Archived from the original on 25 February 2009. Retrieved 2009-02-24. 8. ^ a b McCarey AG (March 1952). "Balantidiasis in South Persia". Br Med J. 1 (4759): 629–31. doi:10.1136/bmj.1.4759.629. PMC 2023172. PMID 14905008. 9. ^ Mason CW (1919). "A Case of Balantidium coli Dysentery". Journal of Parasitology. 5 (3): 137–8. doi:10.2307/3271167. JSTOR 3271167. 10. ^ a b c Parasites and Health: Balantidiasis Balantidium coli. Archived 2013-12-03 at the Wayback Machine DPDx - Balantidiasis. 5 Dec. 2008. CDC Division of Parasitic Diseases. 16 May 2009 >. 11. ^ Ramachandran, Ambili. "Epidemiology of Balantidiasis." The Parasite: Balantidium coli The Disease: Balantidiasis. 23 May 2003. Stanford University. 16 May 2009 <http://www.stanford.edu/group/parasites/ParaSites2003/Balantidium/Epidemiology.htm>. 12. ^ Prevention, CDC - Centers for Disease Control and. "CDC - Balatidiasis - Biology". www.cdc.gov. Retrieved 2018-04-27. 13. ^ a b Nakauchi, Kiyoshi. "The Prevalence of Balantidium coli Infection in Fifty-Six Mammalian Species." Journal of Veterinary Medical Science 61 (1999): 63-65. ## External links[edit] Classification D * ICD-10: A07.0 * ICD-9-CM: 007.0 * MeSH: D001447 * DiseasesDB: 31216 External resources * eMedicine: med/203 * Orphanet: 1223 * v * t * e Protozoan infection: SAR and Archaeplastida SAR Alveolate Apicomplexa Conoidasida/ Coccidia * Coccidia: Cryptosporidium hominis/Cryptosporidium parvum * Cryptosporidiosis * Cystoisospora belli * Isosporiasis * Cyclospora cayetanensis * Cyclosporiasis * Toxoplasma gondii * Toxoplasmosis Aconoidasida * Plasmodium falciparum/vivax/ovale/malariae/knowlesi * Malaria * Blackwater fever * Babesia * Babesiosis Ciliophora * Balantidium coli * Balantidiasis Heterokont * Blastocystis * Blastocystosis * Pythium insidiosum * Pythiosis Archaeplastida * Algaemia: Prototheca wickerhamii * Protothecosis *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Balantidiasis

c0004692

wikipedia

https://en.wikipedia.org/wiki/Balantidiasis

{"gard": ["809"], "mesh": ["D001447"], "umls": ["C0004692"], "wikidata": ["Q2447562"]}

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Oligoastrocytoma" – news · newspapers · books · scholar · JSTOR (May 2011) (Learn how and when to remove this template message) Oligoastrocytoma A oligoastrocytoma on CT SpecialtyOncology Oligoastrocytomas are a subset of brain tumors that present with an appearance of mixed glial cell origin, astrocytoma and oligodendroglioma.[1] However, the term "Oligoastrocytoma" is now considered obsolete by the National Comprehensive Cancer Network[2] stating "the term should no longer be used as such morphologically ambiguous tumors can be reliable resolved into astrocytomas and oligodendrogliomas with molecular testing." These types of glial cells that become cancerous are involved with insulating and regulating the activity of neuron cells in the central nervous system. Often called a "mixed glioma", about 2.3% of all reported brain tumors are diagnosed as oligoastrocytoma.[citation needed] The median age of diagnosis is 42.5.[citation needed] Oligoastrocytomas, like astrocytomas and oligodendrogliomas, can be divided into low-grade and anaplastic variant, the latter characterized by high cellularity, conspicuous cytologic atypism, mitotic activity and, in some cases, microvascular proliferation and necrosis. However, lower grades can have less aggressive biology. These are largely supratentorial tumors of adulthood that favor the frontal and temporal lobes. ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 References * 6 External links ## Signs and symptoms[edit] There are many possible symptoms of oligodendrogliomas that are similar to other gliomas. These symptoms may include headache, seizure and speech or motor changes. ## Diagnosis[edit] A oligoastrocytoma on MRI An X-ray computed tomography (CT) or magnetic resonance imaging (MRI) scan is necessary to characterize the anatomy of this tumor as to size, location, and its heter/homogeneity. However, final diagnosis of this tumor, like most tumors, relies on histopathologic examination (biopsy examination).[citation needed] ## Treatment[edit] If resected, the surgeon will remove as much of this tumor as possible, without disturbing eloquent regions of the brain (speech/motor cortex) and other critical brain structure. Thereafter, treatment may include chemotherapy and radiation therapy of doses and types ranging based upon the patient's needs. Subsequent MRI examination are often necessary to monitor the resection cavity. ## Prognosis[edit] Even after surgery, an oligoastrocytoma will often recur. The treatment for a recurring brain tumor may include surgical resection, chemotherapy and radiation therapy. Survival time of this brain tumor varies; younger age and low-grade initial diagnosis are factors in improved survival time. ## References[edit] 1. ^ Hiremath GK, Bingaman WE, Prayson RA, Nair D (September 2007). "Oligoastrocytoma presenting with intractable epilepsy". Epileptic Disord. 9 (3): 315–22. doi:10.1684/epd.2007.0117 (inactive 2021-01-10). PMID 17884756.CS1 maint: DOI inactive as of January 2021 (link) 2. ^ "NCCN Guidelines: Central Nervous System Cancers" (PDF). www.nccn.org. National Comprehensive Cancer Network. Retrieved 20 August 2018. ## External links[edit] Classification D * ICD-10: Xxx.x * ICD-9-CM: xxx * Brain and Spinal Tumors: Hope Through Research from the U.S. (National Institute of Neurological Disorders and Stroke) * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Oligoastrocytoma

c0280793

wikipedia

https://en.wikipedia.org/wiki/Oligoastrocytoma

{"gard": ["9769"], "mesh": ["D009837"], "orphanet": ["251656"], "wikidata": ["Q1938668"]}

Vitamin K deficiency SpecialtyEndocrinology Symptomsbruising, petechiae, hematomas, oozing of blood at surgical or puncture sites, stomach pains, cartilage calcification, and severe malformation of developing bone or deposition of insoluble calcium salts in the walls of arteries. Causesinsufficient dietary vitamin K1 or vitamin K2 or both Medicationphytonadione Vitamin K deficiency results from insufficient dietary vitamin K1 or vitamin K2 or both.[1] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Epidemiology * 4 See also * 5 References * 6 External links ## Signs and symptoms[edit] Symptoms include bruising,[2] petechiae,[2][3] hematomas,[2] oozing of blood at surgical or puncture sites, stomach pains; risk of massive uncontrolled bleeding; cartilage calcification; and severe malformation of developing bone or deposition of insoluble calcium salts in the walls of arteries. In infants, it can cause some birth defects such as underdeveloped face, nose, bones, and fingers.[2] Vitamin K is changed to its active form in the liver by the enzyme Vitamin K epoxide reductase. Activated vitamin K is then used to gamma carboxylate (and thus activate) certain enzymes involved in coagulation: Factors II, VII, IX, X, and protein C and protein S. Inability to activate the clotting cascade via these factors leads to the bleeding symptoms mentioned above.[citation needed] Notably, when one examines the lab values in Vitamin K deficiency [see below] the prothrombin time is elevated, but the partial thromboplastin time is normal or only mildly prolonged. This may seem counterintuitive given that the deficiency leads to decreased activity in factors of both the intrinsic pathway (F-IX) which is monitored by PTT, as well as the extrinsic pathway (F-VII) which is monitored by PT. However, factor VII has the shortest half-life of all the factors carboxylated by vitamin K; therefore, when deficient, it is the PT that rises first, since the activated Factor VII is the first to "disappear." In later stages of deficiency, the other factors (which have longer half lives) are able to "catch up," and the PTT becomes elevated as well. ## Cause[edit] Vitamin K1-deficiency may occur by disturbed intestinal uptake (such as would occur in a bile duct obstruction), by therapeutic or accidental intake of a vitamin K1-antagonist such as warfarin, or, very rarely, by nutritional vitamin K1 deficiency. As a result, Gla-residues are inadequately formed and the Gla-proteins are insufficiently active.[citation needed] ## Epidemiology[edit] The prevalence of vitamin K deficiency varies by geographic region. For infants in the United States, vitamin K1 deficiency without bleeding may occur in as many as 50% of infants younger than 5 days old, with the classic hemorrhagic disease occurring in 0.25-1.7% of infants.[2] Therefore, the Committee on Nutrition of the American Academy of Pediatrics recommends that 0.5 to 1.0 mg Vitamin K1 be administered to all newborns shortly after birth.[4] Postmenopausal and elderly women in Thailand have high risk of Vitamin K2 deficiency, compared with the normal value of young, reproductive females.[5] Current dosage recommendations for Vitamin K may be too low.[6] The deposition of calcium in soft tissues, including arterial walls, is quite common, especially in those suffering from atherosclerosis, suggesting that Vitamin K deficiency is more common than previously thought.[7] Because colonic bacteria synthesize a significant portion of the Vitamin K required for human needs, individuals with disruptions to or insufficient amounts of these bacteria can be at risk for Vitamin K deficiency. Newborns, as mentioned above, fit into this category, as their colons are frequently not adequately colonized in the first five to seven days of life. Another at-risk population comprises those individuals on any sort of long-term antibiotic therapy, as this can diminish the population of normal gut flora.[citation needed] ## See also[edit] * Haemorrhagic disease of the newborn ## References[edit] 1. ^ "Vitamin K Deficiency: Background, Physiology, Complications and Prognosis". Cite journal requires `|journal=` (help) 2. ^ a b c d e Vitamin K Deficiency eMedicine. Author: Pankaj Patel, MD. Coauthor(s): Mageda Mikhail, MD, Assistant Professor. Updated: Feb 13, 2014 3. ^ "Causes". 4. ^ American Academy of Pediatrics – Committee on Fetus and Newborn (July 2003). "Controversies concerning vitamin K and the newborn". Pediatrics. 112 (1): 191–2. doi:10.1542/peds.112.1.191. PMID 12837888. 5. ^ Bunyaratavej N (2007). "[Experience of vitamin K2 in Thailand]". Clin Calcium (in Japanese). 17 (11): 1752–60. PMID 17982197. 6. ^ Adams J, Pepping J (2005). "Vitamin K in the treatment and prevention of osteoporosis and arterial calcification". Am J Health Syst Pharm. 62 (15): 1574–81. doi:10.2146/ajhp040357. PMID 16030366. 7. ^ Berkner KL, Runge KW (2004). "The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis". J. Thromb. Haemost. 2 (12): 2118–32. doi:10.1111/j.1538-7836.2004.00968.x. PMID 15613016. ## External links[edit] Classification D * ICD-10: E56.1 * ICD-9-CM: 269.0 * MeSH: D014813 * DiseasesDB: 13962 External resources * eMedicine: med/2385 * Patient UK: Vitamin K deficiency * v * t * e Malnutrition Protein-energy malnutrition * Kwashiorkor * Marasmus * Catabolysis Vitamin deficiency B vitamins * B1 * Beriberi * Wernicke–Korsakoff syndrome * Wernicke's encephalopathy * Korsakoff's syndrome * B2 * Riboflavin deficiency * B3 * Pellagra * B6 * Pyridoxine deficiency * B7 * Biotin deficiency * B9 * Folate deficiency * B12 * Vitamin B12 deficiency Other * A: Vitamin A deficiency * Bitot's spots * C: Scurvy * D: Vitamin D deficiency * Rickets * Osteomalacia * Harrison's groove * E: Vitamin E deficiency * K: Vitamin K deficiency Mineral deficiency * Sodium * Potassium * Magnesium * Calcium * Iron * Zinc * Manganese * Copper * Iodine * Chromium * Molybdenum * Selenium * Keshan disease Growth * Delayed milestone * Failure to thrive * Short stature * Idiopathic General * Anorexia * Weight loss * Cachexia * Underweight * v * t * e Conditions originating in the perinatal period / fetal disease Maternal factors complicating pregnancy, labour or delivery placenta * Placenta praevia * Placental insufficiency * Twin-to-twin transfusion syndrome chorion/amnion * Chorioamnionitis umbilical cord * Umbilical cord prolapse * Nuchal cord * Single umbilical artery presentation * Breech birth * Asynclitism * Shoulder presentation Growth * Small for gestational age / Large for gestational age * Preterm birth / Postterm pregnancy * Intrauterine growth restriction Birth trauma * scalp * Cephalohematoma * Chignon * Caput succedaneum * Subgaleal hemorrhage * Brachial plexus injury * Erb's palsy * Klumpke paralysis Affected systems Respiratory * Intrauterine hypoxia * Infant respiratory distress syndrome * Transient tachypnea of the newborn * Meconium aspiration syndrome * Pleural disease * Pneumothorax * Pneumomediastinum * Wilson–Mikity syndrome * Bronchopulmonary dysplasia Cardiovascular * Pneumopericardium * Persistent fetal circulation Bleeding and hematologic disease * Vitamin K deficiency bleeding * HDN * ABO * Anti-Kell * Rh c * Rh D * Rh E * Hydrops fetalis * Hyperbilirubinemia * Kernicterus * Neonatal jaundice * Velamentous cord insertion * Intraventricular hemorrhage * Germinal matrix hemorrhage * Anemia of prematurity Gastrointestinal * Ileus * Necrotizing enterocolitis * Meconium peritonitis Integument and thermoregulation * Erythema toxicum * Sclerema neonatorum Nervous system * Perinatal asphyxia * Periventricular leukomalacia Musculoskeletal * Gray baby syndrome * muscle tone * Congenital hypertonia * Congenital hypotonia Infections * Vertically transmitted infection * Neonatal infection * rubella * herpes simplex * mycoplasma hominis * ureaplasma urealyticum * Omphalitis * Neonatal sepsis * Group B streptococcal infection * Neonatal conjunctivitis Other * Miscarriage * Perinatal mortality * Stillbirth * Infant mortality * Neonatal withdrawal *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Vitamin K deficiency

c0042880

wikipedia

https://en.wikipedia.org/wiki/Vitamin_K_deficiency

{"mesh": ["D014813"], "umls": ["C0042880"], "wikidata": ["Q4138767"]}

A number sign (#) is used with this entry because of evidence that O'Donnell-Luria-Rodan syndrome (ODLURO) is caused by heterozygous mutation in the KMT2E gene (608444) on chromosome 7q22. Description O'Donnell-Luria-Rodan syndrome (ODLURO) is a neurodevelopmental disorder characterized by global developmental delay, speech delay, variably delayed intellectual development, and subtle dysmorphic features. Some patients may have autism, seizures, hypotonia, and/or feeding difficulties (summary by O'Donnell-Luria et al., 2019). Clinical Features O'Donnell-Luria et al. (2019) reported 30 individuals, most of whom were in the first decade of life, with a similar neurodevelopmental disorder associated with heterozygous protein-truncating variants in the KMT2E gene. A few of the patients had previously been reported in other larger studies. Available history of all patients indicated global developmental delay from infancy, with the average age of walking and first word at 20 months (range 12 to 48 months). Many had hypotonia, but all could walk independently, and most were verbal, although several had speech difficulties. IQ data available for 7 patients showed a mean of 74 (range 62-98). Seven patients were diagnosed with autism, and several others had attention-deficit/hyperactivity disorder (ADHD) or other behavioral concerns, such as stereotypies, skin-picking behavior, self-injurious behavior, aggression, and/or anxiety. About half had mild macrocephaly, although other growth parameters were normal. One patient had neonatal ischemic encephalopathy associated with seizures, but otherwise, only 4 patients had epilepsy, most of which was controlled. Brain imaging was normal or showed nonspecific findings, such as abnormal corpus callosum, signal abnormalities in the white matter, decreased volume, delayed myelination, small areas of heterotopia, or small localized cysts. Many patients had gastrointestinal symptoms, including reflux, vomiting, or bowel motility issues. Most patients had subtle dysmorphic features, including dolichocephaly, large forehead, deep-set eyes, downslanting palpebral fissures, periorbital fullness, prominent cheeks, and prominent nasolabial folds. Rare features included cardiac septal defects, neonatal jaundice, kyphosis, tapering fingers, and cryptorchidism. There were 4 additional patients with heterozygous missense mutations, which was associated with a more severe phenotype. All of these patients had epilepsy, including 3 with infantile epileptic encephalopathy, and all had more severe global developmental delay compared to patients with truncating mutations. All 4 were nonverbal, 2 had microcephaly, and only 2 could walk. Four additional patients with a similar phenotype had larger heterozygous deletions of chromosome 7q22 that encompassed the KMT2E gene. O'Donnell-Luria et al. (2019) noted that most (70%) of the patients were male, and expressivity was variable by sex: affected females tended to have epilepsy, whereas affected males tended to have autism. Molecular Genetics In 34 individuals with ODLURO, O'Donnell-Luria et al. (2019) identified heterozygous mutations in the KMT2E gene (see, e.g., 608444.0001-608044.0006). The patients were ascertained through collaboration of several research centers, and the mutations were found by exome or genome sequencing. Most of the mutations resulted in a truncated protein, consistent with haploinsufficiency, although 4 patients carried missense mutations that affected highly conserved residues. The vast majority of the mutations occurred de novo, although there was 1 family with 3 affected sibs who may have inherited the variant from an affected father; DNA from the father was not available. Functional studies of the variants and studies of patient cells were not performed, but the authors postulated haploinsufficiency for KMT2E as the pathogenic mechanism for the protein-truncating mutations, and altered KMT2E binding properties for the missense mutations. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly \- Dolichocephaly Face \- Dysmorphic facial features, mild \- Prominent forehead \- Full cheeks \- Prominent nasolabial folds Eyes \- Deep-set eyes \- Downslanting palpebral fissures \- Periorbital fullness ABDOMEN Gastrointestinal \- Feeding difficulties \- Gastrointestinal reflux \- Vomiting \- Bowel motility issues GENITOURINARY External Genitalia (Male) \- Cryptorchidism SKELETAL Spine \- Kyphosis Hands \- Tapering fingers SKIN, NAILS, & HAIR Skin \- Neonatal jaundice MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Global developmental delay \- Delayed walking, mild \- Impaired intellectual development, variable \- Speech delay, mild \- Articulation difficulties \- Seizures (in some patients) \- Epileptic encephalopathy (rare) \- Brain imaging abnormalities, variable, nonspecific \- Abnormal corpus callosum \- White matter abnormalities \- Delayed myelination \- Small localized cysts Behavioral Psychiatric Manifestations \- Autistic features \- Attention-deficit/hyperactivity disorder (ADHD) \- Stereotypies \- Skin-picking \- Self-injurious behavior \- Aggression \- Anxiety MISCELLANEOUS \- Onset in infancy \- Variable phenotype and severity \- De novo mutation (in most patients) MOLECULAR BASIS \- Caused by mutation in the lysine-specific methyltransferase 2E gene (KMT2E, 608444.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

O'DONNELL-LURIA-RODAN SYNDROME

None

omim

https://www.omim.org/entry/618512

{"omim": ["618512"]}

MECP2 duplication syndrome Other namesX-linked intellectual disability-hypotonia-recurrent Infections syndrome This condition is due to MECP2 overexpression SpecialtyMedical genetics MECP2 duplication syndrome (M2DS) is a rare disease that is characterized by severe intellectual disability and impaired motor function. It is an X-linked genetic disorder caused by the overexpression of MeCP2 protein. ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Management * 5 Epidemiology * 6 History * 7 References * 8 Further reading * 9 External links ## Signs and symptoms[edit] Symptoms of M2DS include infantile hypotonia and failure to thrive, delayed psychomotor development, impaired speech, abnormal or absent gait, epilepsy, spasticity, gastrointestinal motility problems, recurrent infections, and genitourinary abnormalities.[1][2][3] Many of those affected by M2DS also fit diagnostic criteria for autism.[4] M2DS can be associated with syndromic facies, namely an abnormally flat back of the head, underdevelopment of the midface, ear anomalies, deep-set eyes, prominent chin, pointed nose, and a flat nasal bridge.[4] ## Cause[edit] M2DS is one of the several types of X-linked intellectual disability. The cause of M2DS is a duplication of the MECP2 or Methyl CpG binding protein 2 gene located on the X chromosome (Xq28).[5] The MeCP2 protein plays a pivotal role in regulating brain function. Increased levels of MECP2 protein results in abnormal neural function and impaired immune system.[4] Mutations in the MECP2 gene are also commonly associated with Rett syndrome in females. Advances in genetic testing and more widespread use of Array Comparative Genomic Hybridization has led to increased diagnosis of MECP2 duplication syndrome.[6] It is thought to represent ~1% of X-linked male mental disability cases.[7] Females affected by this condition often do not show symptoms.[4] ## Diagnosis[edit] Diagnosis is made based on genetic testing.[4] ## Management[edit] Treatment is supportive and based on symptoms.[4] ## Epidemiology[edit] The syndrome primarily affects young males.[7] Preliminary studies suggest that prevalence may be 1.8 per 10,000 live male births. 50% of those affected do not live beyond 25 years of age, with deaths attributed to the impaired immune function.[8] ## History[edit] M2DS was first described in 1999.[4] In a Nature article published on November 25, 2015, it was revealed that researchers at the Baylor College of Medicine, led by Dr. Huda Y. Zoghbi, have reversed MECP2 Duplication Syndrome in adult symptomatic mice using antisense therapy.[9] Mice treated with an experimental ASO administered through the central nervous system had a reduction of MECP2 protein to normal levels and symptoms of hypoactivity, anxiety, and abnormal social behavior were resolved. Additionally, the seizure activity of the mice and abnormal EEG discharges were abolished. Initial studies demonstrated that reducing the MECP2 protein levels to the correct amount also normalized the expression of the other genes controlled by the MECP2 protein. ## References[edit] 1. ^ "MECP2 duplication syndrome - Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. 2. ^ Ramocki, Melissa B.; Peters, Sarika U.; Tavyev, Y. Jane; Zhang, Feng; Carvalho, Claudia M. B.; Schaaf, Christian P.; Richman, Ronald; Fang, Ping; Glaze, Daniel G.; Lupski, James R.; Zoghbi, Huda Y. (2009). "Autism and other neuropsychiatric symptoms are prevalent in individuals withMeCP2duplication syndrome". Annals of Neurology. 66 (6): 771–782. doi:10.1002/ana.21715. ISSN 0364-5134. PMC 2801873. PMID 20035514. 3. ^ Ramocki, Melissa B.; Tavyev, Y. Jane; Peters, Sarika U. (2010). "TheMECP2duplication syndrome". American Journal of Medical Genetics Part A. 152A (5): 1079–1088. doi:10.1002/ajmg.a.33184. ISSN 1552-4825. PMC 2861792. PMID 20425814. 4. ^ a b c d e f g "MECP2 Duplication Syndrome - NORD (National Organization for Rare Disorders)". 5. ^ Reference, Genetics Home. "MECP2 duplication syndrome". Genetics Home Reference. 6. ^ "Van Wright Foundation". Van Wright Foundation. 7. ^ a b Van Esch, H. (2011). "MECP2 Duplication Syndrome". Molecular Syndromology. 2 (3–5): 128–136. doi:10.1159/000329580. ISSN 1661-8777. PMC 3366699. PMID 22679399. 8. ^ Van Esch, Hilde (7 June 1993). Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E.; Bean, Lora J.H.; Stephens, Karen; Amemiya, Anne (eds.). GeneReviews®. University of Washington, Seattle. PMID 20301461 – via PubMed. 9. ^ Sztainberg, Yehezkel; Chen, Hong-mei; Swann, John W.; Hao, Shuang; Tang, Bin; Wu, Zhenyu; Tang, Jianrong; Wan, Ying-Wooi; Liu, Zhandong; Rigo, Frank; Zoghbi, Huda Y. (25 November 2015). "Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides". Nature. 528 (7580): 123–126. Bibcode:2015Natur.528..123S. doi:10.1038/nature16159. PMC 4839300. PMID 26605526. ## Further reading[edit] * Samaco, Rodney C; Mandel-Brehm, Caleigh; McGraw, Christopher M; Shaw, Chad A; McGill, Bryan E; Zoghbi, Huda Y (2012). "Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome". Nature Genetics. 44 (2): 206–211. doi:10.1038/ng.1066. ISSN 1061-4036. PMC 3267865. PMID 22231481. * Francesca Ariani; Francesca Mari; Chiara Pescucci; Ilaria Longo; Mirella Bruttini; Ilaria Meloni; Giuseppe Hayek; Raffaele Rocchi; Michele Zappella & Alessandra Renieri (August 2004). "Real-time quantitative PCR as a routine method for screening large rearrangements in Rett syndrome: Report of one case of MECP2 deletion and one case of MECP2 duplication". Human Mutation. 24 (2): 172–177. doi:10.1002/humu.20065. PMID 15241799. * Chahrour, M.; Jung, S. Y.; Shaw, C.; Zhou, X.; Wong, S. T. C.; Qin, J.; Zoghbi, H. Y. (2008). "MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription". Science. 320 (5880): 1224–1229. Bibcode:2008Sci...320.1224C. doi:10.1126/science.1153252. ISSN 0036-8075. PMC 2443785. PMID 18511691. ## External links[edit] Classification D * ICD-10: Q87.8 * OMIM: 300260 * MeSH: C537723 * DiseasesDB: ddb34533 External resources * Orphanet: 85281 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

MECP2 duplication syndrome

c1846058

wikipedia

https://en.wikipedia.org/wiki/MECP2_duplication_syndrome

{"gard": ["9781"], "mesh": ["C537723"], "umls": ["C1846058"], "orphanet": ["85281"], "wikidata": ["Q24975607"]}

## Summary ### Clinical characteristics. Hepatoerythropoietic porphyria (HEP) is characterized by blistering skin lesions, hypertrichosis, and scarring over the affected skin areas. Disease manifestations occur during infancy or childhood and with similar frequency in females and males. Individuals with HEP are not reported to be at increased risk for hepatocellular carcinoma. ### Diagnosis/testing. The diagnosis of HEP is established in a proband by identification of elevated porphyrins in the urine (predominantly uroporphyrin and heptacarboxylporphyrin) and significantly increased erythrocyte zinc protoporphyrin. Identification of biallelic pathogenic variants in UROD confirms the diagnosis. ### Management. Treatment of manifestations: Avoidance of sunlight (including the long-wave ultraviolet light sunlight that passes through window glass) by use of protective clothing and topical application of opaque sunscreens. Phlebotomy and chloroquine, which are usually effective in treating familial porphyria cutanea tarda, are generally less effective in individuals with HEP. Prevention of primary manifestations: Protection from sunlight. Agents/circumstances to avoid: Exposure to sunlight in persons of all ages. Older individuals should avoid known precipitating factors: alcohol, oral estrogen, smoking, and drugs that induce the cytochrome P450s. Evaluation of relatives at risk: If the family-specific UROD pathogenic variants are known, clarify the genetic status of at-risk relatives so that those with biallelic UROD pathogenic variants can be counseled regarding sun protection and avoidance of known susceptibility factors. ### Genetic counseling. HEP is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being heterozygous and at risk of developing familial porphyria cutanea tarda, and a 25% chance of being unaffected and not heterozygous. Once the UROD pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for HEP are possible. ## Diagnosis ### Suggestive Findings Hepatoerythropoietic porphyria (HEP) should be considered in individuals who present during infancy or childhood with the following clinical features and laboratory findings. Clinical features * Blistering skin lesions * Hypertrichosis * Scarring * Passage of red urine Note: The features of HEP generally resemble those of congenital erythropoietic porphyria. Laboratory findings (see Table 1) * Hepatic uroporphyrinogen decarboxylase (UROD) enzyme activity is approximately 15%-20% of normal. * The UROD protein level is determined by genotype (e.g., ~50% in individuals with a null allele and a partial loss-of-function allele). * Erythrocyte zinc protoporphyrin levels are significantly increased. * Plasma porphyrins are increased. Fluorescence emission peaks (at neutral pH) at approximately 620 nm following excitation with light of approximately 400-410 nm (Soret band) [Poh-Fitzpatrick & Lamola 1976]. * Porphyrins are elevated in the urine. There is a predominance of uroporphyrin and heptacarboxylporphyrin; hexa- and pentacarboxylporphyrins and coproporphyrin levels are also increased. Note: Isomer analysis of the uroporphyrin shows a significant increase in isomer I uroporphyrin. * Levels of fecal isocoproporphyrin and hepta- and pentaporphyrins are increased. * Urine delta-aminolevulinic acid (ALA) is normal or minimally increased. * Porphobilinogen (PBG) levels are normal. ### Table 1. Biochemical Characteristics of Hepatoerythropoietic Porphyria View in own window Biochemical Finding Deficient enzymeUroporphyrinogen decarboxylase Enzyme activity~15%-20% of normal Erythrocytes↑ Zinc protoporphyrin Plasma↑ Uroporphyrin, heptacarboxylporphyrin (~620 nm) 1 Urine↑ Uroporphyrin, heptacarboxylporphyrin Stool↑ Heptacarboxylporphyrin, isocoproporphyrins + pentacarboxylporphyrins 1\. Fluorescence emission peak of diluted plasma at neutral pH, following excitation at 400-410 nm Note: Histologic findings on skin biopsy are not diagnostic of HEP. ### Establishing the Diagnosis The diagnosis of HEP is established in a proband by the presence of increased uroporphyrin and heptacarboylporphyrin in the urine in addition to significantly increased erythrocyte zinc protoporphyrin, and/or by the identification of biallelic pathogenic variants in UROD (see Table 2). Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing: * Single-gene testing. Sequence analysis of UROD is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found. * A multigene panel that includes UROD and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. * More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if serial single-gene testing (and/or use of a multigene panel that includes UROD) fails to confirm a diagnosis in an individual with features of HEP. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 2. Molecular Genetic Testing Used in Hepatoerythropoietic Porphyria View in own window Gene 1Test MethodProportion of Probands with Pathogenic Variants 2 Detectable by This Method URODSequence analysis 314/16 4, 5 Gene-targeted deletion/duplication analysis 62/16 7 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Author communication 5\. Additional variants associated with F-PTC have been detected. 6\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 7\. Large deletions involving UROD have been described in HEP, including deletion of the entire gene in one individual [de Verneuil et al 1992] and a 1-kb deletion in another [Mendez et al 1998]. Cantatore-Francis et al [2010] described compound heterozygosity for a complex deletion/insertion allele and a pathogenic missense variant. ## Clinical Characteristics ### Clinical Description Clinical manifestations of HEP include extreme photosensitivity, skin lesions with fluid-filled blisters that break and heal slowly, hypertrichosis, and scarring over the affected skin areas. Repeated sun exposure can lead to scleroderma-like changes that result in photomutilation [Elder 1997]. With high levels of circulating porphyrins there may be a red/brown discoloration of teeth due to the deposition of porphyrins in the enamal layer of the developing tooth. Signs and symptoms of HEP start during infancy or childhood, with similar frequency in females and males, and generally resemble those of congenital erythropoietic porphyria. Note: The clinical features of porphyria cutanea tarda (PCT) (see Differential Diagnosis) and HEP are indistinguishable. No increased risk for hepatocellular carcinoma has been identified in persons with HEP. Susceptibility factors. The rare nature of this disease makes identification of additional risk factors difficult to assess; however, the same susceptibility factors shown to modulate the phenotype of familial porphyria cutanea tarda (F-PCT) are likely to be important in HEP (see Differential Diagnosis) [Bonkovsky et al 2013]. Susceptibility factors to some extent reflect their frequency in the general population to which the individual belongs. The frequency and the degree to which these risk factors are involved in type I PCT (sporadic) and F-PCT also differ in HEP [Aarsand et al 2009, Muñoz-Santos et al 2010]. The genetic and environmental susceptibility factors may reflect their frequency in the general population (e.g., hepatitis C infection, HFE pathogenic variant). * Iron and HFE pathogenic variants. Mild-to-moderate iron overload is typically found in persons with F-PCT; some degree of hepatic siderosis is seen in almost all affected individuals. * Alcohol. PCT has long been associated with excessive alcohol use. * Smoking and cytochrome P450 enzymes. Smoking is commonly associated with alcohol use in PCT [Egger et al 2002]. * Hepatitis C. Reported prevalence of hepatitis C in individuals with PCT has ranged from 21% to 92% in various countries [Ryan Caballes et al 2012]; it is seen more frequently in type I PCT than in F- PCT [Muñoz-Santos et al 2010]. Note that the frequency in HEP has not been determined. * Estrogens. Estrogen use is a common susceptibility factor in women with PCT [Grossman et al 1979, Sixel-Dietrich & Doss 1985, Egger et al 2002] and also presents a risk for men (e.g., those taking estrogen for treatment of prostatic cancer). Discontinuation of oral estrogen use leads to resolution of the symptoms. Use of transdermal estrogens in women has been shown to be safe [Bulaj et al 2000]. * Antioxidants. Substantial reductions in plasma levels of ascorbate and carotenoids have been noted in some individuals with PCT [Percy et al 1975, Sinclair et al 1997, Rocchi et al 1999]. ### Pathophysiology UROD deficiency (in all tissues) leads to the accumulation of substrate, uroporphyrinogen, and the intermediate products of the reaction in all cells. Cells with a high demand for heme production include the erythron and the hepatocyte, and thus, accumulation may be more pronounced in these cell types. The substrates and intermediates accumulate in cells in the form of oxidized porphyrins (mostly uroporphyrin and heptacarboxylporphyrin) that are then transported into the plasma and eventually into the urine. These excess porphyrins are deposited in the skin and other tissues. For more information about the proposed pathophysiology of HEP, click here. ### Genotype-Phenotype Correlations No clinically significant genotype-phenotype correlations have been found (see Molecular Genetics). ### Nomenclature ### Prevalence Fewer than 100 cases of HEP have been reported in the literature. The frequency of HEP can only be inferred based on that of familial PCT, which occurs in one in 20,000. ## Differential Diagnosis Type I porphyria cutanea tarda (sporadic; no UROD pathogenic variant). Type I porphyria cutanea tarda (PCT) is highly influenced by susceptibility factors associated with PCT; often several are present in individuals with type I PCT, including a pathogenic variant in HFE. Type I PCT is clinically indistinguishable from HEP and familial PCT. Familial porphyria cutanea tarda (F-PCT). The skin lesions of F-PCT resemble those of HEP, however they are less severe. The skin changes of F-PCT typically begin later, in the fourth or fifth decade of life. Disease manifestations are more common in men than women. Because the laboratory findings in individuals with F-PCT and HEP can be clinically indistinguishable at the time of diagnosis, molecular genetic testing is necessary to discriminate between these two disorders. Measurement of UROD enzyme activity is not an accurate method to distinguish between F-PCT and HEP. Heterozygous UROD pathogenic variants are causative. Inheritance is autosomal dominant with reduced penetrance. Variegate porphyria (VP) and hereditary coproporphyria (HCP). Blistering skin lesions in VP and HCP are nearly identical to those in HEP. Although the cutaneous manifestations of HEP are also chronic and blistering, they are usually more severe than those of VP because circulating porphyrin levels are usually much higher (by an order of magnitude) than in VP. HCP is generally accompanied by neurovisceral features, especially bouts of severe abdominal pain, which are not observed in HEP. In both HCP and VP, the principal source of overproduction of heme precursors is the liver. VP is caused by a heterozygous pathogenic variant in PPOX and HCP is caused by a heterozygous pathogenic variant in CPOX. Both disorders are inherited in an autosomal dominant manner with low penetrance. Although mild manifestations of HEP can be mistaken for those of VP and HCP, the erythropoietic porphyrias (e.g., HEP, CEP, or EPP) are differentiated particularly by the presence of high levels of erythrocyte porphyrins. Congenital erythropoietic porphyria (CEP). The skin lesions of CEP, like those seen in HEP, appear early in life (i.e., in infancy or childhood) and are severe and mutilating. In both CEP and HEP the increased severity is attributed to the plasma concentration of porphyrin. Although CEP can be mistaken for HEP, urine porphyrin analysis (which demonstrates uroporphyrin and coproporphyrin type I) rules out other types of cutaneous porphyria. Fecal analysis may be necessary, particularly for late-onset cases. CEP caused by biallelic pathogenic variants in UROS is inherited in an autosomal recessive manner; CEP caused by a hemizygous pathogenic variant in GATA1 (rare) is inherited in an X-linked manner. Pseudoporphyria. Although the skin histopathologic findings of pseudoporphyria are indistinguishable from those of HEP, pseudoporphyria does not cause porphyrin biochemical abnormalities. Drugs are implicated in the appearance of this condition [Barzilay et al 2001]. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with hepatoerythropoietic porphyria (HEP), the following evaluations are recommended: * Evaluation for excess hepatic iron * Targeted analysis for HFE pathogenic variants (see HFE hemochromatosis) * Consultation with a clinical geneticist and/or genetic counselor ### Treatment of Manifestations There are no effective treatment regimens to restore enzyme levels in individuals with HEP. Hence, treatment recommendations at this time are similar to the ones for familial porphyria cutanea tarda (F-PCT): the avoidance of sunlight, including the long-wave ultraviolet light sunlight that passes through window glass. ### Prevention of Primary Manifestations The following measures are recommended: * Protection from sunlight because of the high risk for severe skin damage and possible mutilation * Identification and avoidance of susceptibility factors (where applicable) . See Agents/Circumstances to Avoid. * Avoidance of drugs and agents that induce the hepatic P450 * Vaccination against hepatitis A and B ### Surveillance There are currently no recommendations or guidelines for surveillance in those with HEP. ### Agents/Circumstances to Avoid Persons of all ages should avoid exposure to sunlight. Older individuals should avoid the known precipitating factors (e.g., alcohol, oral estrogen, smoking, and drugs that induce the cytochrome P450s). ### Evaluation of Relatives at Risk If the family-specific UROD pathogenic variants are known, it is reasonable to clarify the genetic status of at-risk relatives so that those with biallelic UROD pathogenic variants can be counseled regarding sun protection and avoidance of known susceptibility factors. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Hepatoerythropoietic Porphyria

c0162569

gene_reviews

https://www.ncbi.nlm.nih.gov/books/NBK169003/

{"mesh": ["D017121"], "synonyms": []}

A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by the association of auricular abnormalities (such as external ear abnormalities and postauricular pits) and cleft lip with or without cleft palate. Additional manifestations include myopia, nystagmus, and retinal pigment abnormalities. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Auricular abnormalities-cleft lip with or without cleft palate-ocular abnormalities syndrome

None

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77300

{"icd-10": ["Q87.0"]}

A number sign (#) is used with this entry because of evidence that autosomal recessive mental retardation-50 (MRT50) is caused by homozygous mutation in the EDC3 gene (609842) on chromosome 15q24. One such family has been reported. Clinical Features Ahmed et al. (2015) reported 2 sibs, born of consanguineous Syrian parents, with nonsyndromic mental retardation. After normal development in the first year of life, both showed impaired cognitive development with unremarkable motor development. Both had microcephaly (down to -3.6 SD), but no other dysmorphic features. One patient had sensory hearing loss, poor language, and sectoral heterochromia iridum. Inheritance The transmission pattern of MRT50 in the family reported by Ahmed et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs, born of consanguineous Syrian parents, with mild autosomal recessive mental retardation, Ahmed et al. (2015) identified a homozygous missense mutation in the EDC3 gene (F54S; 609842.0001). The mutation, which was found by homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that whereas wildtype protein enhanced DCP2 (609844) decapping activity, the mutant protein did not. Ahmed et al. (2015) postulated that this would lead to aberrant cellular accumulation of mRNA, which could have adverse effects on neuronal function. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (down to -3.6 SD) Ears \- Sensorineural hearing loss (1 patient) NEUROLOGIC Central Nervous System \- Intellectual disability, mild MISCELLANEOUS \- Onset in first year of life \- Two sibs from a consanguineous Syrian family have been reported (last curated July 2015) MOLECULAR BASIS \- Caused by mutation in the enhancer of mRNA decapping 3, S. cerevisiae, homolog of, gene (EDC3, 609842.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

MENTAL RETARDATION, AUTOSOMAL RECESSIVE 50

c4225319

omim

https://www.omim.org/entry/616460

{"omim": ["616460"], "orphanet": ["88616"], "synonyms": ["AR-NSID", "NS-ARID"]}

A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-56 (RP56) is caused by homozygous mutation in the gene encoding interphotoreceptor matrix proteoglycan-2 (IMPG2; 607056) on chromosome 3q12. For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa (RP), see 268000. Clinical Features Bandah-Rozenfeld et al. (2010) examined 12 patients from 7 families with retinal disease and mutations in the IMPG2 gene. In general, affected individuals with IMPG2 mutations displayed typical symptoms and signs of RP, including night blindness, visual field loss, optic disc pallor, attenuated vessels, and bone-spicule-like pigmentation. In 11 of the 12 patients, lens abnormalities were observed: 7 had posterior subcapsular cataracts, 2 had mild cortical cataracts, 1 had pseudophakia, and 1 patient, who was diagnosed with mild maculopathy (see VMD5, 616152) rather than RP, had mild nuclear sclerosis. Mapping Using whole-genome SNP analysis of 381 patients with RP and 193 patients with Leber congenital amaurosis (LCA; see 204000) of Israeli, Palestinian, and European origin, Bandah-Rozenfeld et al. (2010) identified 2 RP families in which the affected sibs shared a large homozygous region at chromosome 3q12. The 7.2-Mb overlapping interval, flanked by rs12330531 and rs326333, contained 30 annotated genes, including the IMPG2 gene. Molecular Genetics In an Iraqi Jewish family and a Dutch family, both segregating autosomal recessive RP mapping to chromosome 3q12, Bandah-Rozenfeld et al. (2010) analyzed the IMPG2 gene and identified homozygosity for a nonsense mutation (S212X; 607056.0001) and a 1.8-kb genomic deletion (607056.0002), respectively. Analysis of IMPG2 in 10 additional families segregating autosomal recessive retinal disease mapping to chromosome 3q12 revealed 5 additional mutations (see, e.g., 607056.0003-607056.0004), including a missense mutation (F124L; 607056.0005) in a patient (family MOL0732) who had only mild maculopathy. The latter patient's phenotype was designated as representing 'a case of autosomal recessive macular vitelliform dystrophy' by Meunier et al. (2014), who identified a heterozygous C1077F mutation (607056.0006) in a father and son with vitelliform macular dystrophy (VMD5; 616152). INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Night blindness \- Visual field loss \- Attenuation of retinal arterioles \- Pigmentary retinopathy with typical bone spicule appearance \- Decreased visual acuity \- Posterior subcapsular cataract MOLECULAR BASIS \- Caused by mutation in the interphotoreceptor matrix proteoglycan 2 gene (IMPG2, 607056.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

RETINITIS PIGMENTOSA 56

c0035334

omim

https://www.omim.org/entry/613581

{"doid": ["0110371"], "mesh": ["D012174"], "omim": ["613581"], "orphanet": ["791"], "genereviews": ["NBK1417"]}

A number sign (#) is used with this entry because X-linked atrophic macular degeneration can be caused by mutation in the RPGR gene (312610). Clinical Features Ayyagari et al. (2002) described a family in which 10 males had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration. Mapping In a family with X-linked recessive atrophic macular degeneration, Ayyagari et al. (2002) mapped the disease locus to Xp21.1-p11.4, the region where the RPGR gene is situated. Molecular Genetics In affected members of a family segregating X-linked recessive atrophic macular degeneration, Ayyagari et al. (2002) identified a splice site mutation in the RPGR gene (312610.0017). INHERITANCE \- X-linked recessive HEAD & NECK Eyes \- Visual acuity loss, progressive \- Central vision loss, progressive \- Macular degeneration \- Hypopigmentated retina without intraretinal pigment clumping \- ERG responses normal to some reduction in cone and rod function MISCELLANEOUS \- Carrier females have subtle perimacular RPE depigmentation \- Based on the report of one family MOLECULAR BASIS \- Caused by mutation in the retinitis pigmentosa GTPase regulator gene (RPGR, 312610.0017 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

MACULAR DEGENERATION, X-LINKED ATROPHIC

c3489532

omim

https://www.omim.org/entry/300834

{"mesh": ["D000071700"], "omim": ["120970", "300834"], "orphanet": ["1872"], "synonyms": []}

A rare, severe, primary bone dysplasia characterized by intrauterine and postnatal growth retardation, microcephaly, facial dysmorphism, skeletal dysplasia, low-birth weight and brain anomalies. ## Epidemiology Less than 60 cases have been described in the literature so far. ## Clinical description The facial dysmorphism is characterized by a round face, metopic ridge, small anterior fontanelle, a sloping forehead, prominent occiput, protruding eyes, prominent nose, small dysplastic ears and micrognathia. The neck is short. Sparse hair and eyebrows, and dry skin are frequently observed. Skeletal anomalies include short limbs, brachydactyly, flexion contractures markedly delayed epiphyseal ossification and, more variably, dislocation of the hips and elbows. The most frequent neurological manifestations are intellectual deficit and seizures, and reported brain anomalies include brain hypoplasia, lissencephaly or pachygyria, hypoplastic frontal lobes, arachnoid cysts, agenesis of the corpus callosum or and mild cerebellar vermis hypoplasia. Cardiac anomalies and retinal dystrophy are more variably reported. ## Etiology Caused by bi-allelic mutations of RNU4ATAC (2q14.2), a gene encoding a small nuclear RNA involved in minor (U12) splicing. Mutations in the same gene also cause Roifman syndrome in which there are many overlapping features but Roifman is distinguished by immunodeficiency. ## Diagnostic methods Diagnosis is made on the basis of the clinical and radiological phenotype including marked growth retardation and microcephaly, severe brain anomalies and common radiological bone features including delayed epiphyseal ossification, short and bowed tubular bones, enlarged metaphyses, elongated clavicles, mild platyspondyly, cleft vertebral arches, short fingers and toes and small iliac wings. ## Differential diagnosis The differential diagnosis should include MOPD type 2 and other syndromes associated with primordial dwarfism, such as Seckel syndrome and microcephalic primordial dwarfism due to RTTN deficiency. ## Antenatal diagnosis Prenatal diagnosis, by ultrasonography showing brain anomalies, IUGR and short distal limb at around 20 weeks of gestation, has been reported in affected families. ## Genetic counseling MOPD type I/III is transmitted as an autosomal recessive trait. Genetic counseling should be offered to at risk families (where each parent is an unaffected carrier) informing them that there is a 25% risk of having an affected child at each pregnancy. ## Management and treatment Treatment is supportive only. Particular attention should be provided to growth and psychomotor development. Medical care and management should be provided according to malformations and intellectual deficiency. Great attention should be paid to apparently mild medical events (fever, drowsiness), especially in the first three years of life. ## Prognosis The prognosis is poor with most of the reported patients dying either in utero or unexpectedly as a result of a fever or an apparently mild medical event within the first 3 years of life. Several RNU4ATAC mutations appear to be compatible with prolonged survival, sometimes until adulthood. * European Reference Network *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Microcephalic osteodysplastic primordial dwarfism types I and III

c1859452

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2636

{"gard": ["5120"], "mesh": ["C537577"], "omim": ["210710", "210730"], "icd-10": ["Q87.1"], "synonyms": ["MOPD types I and III", "Microcephalic osteodysplastic primordial dwarfism, Taybi-Linder type", "Primordial microcephalic dwarfism, Crachami type", "Taybi-Linder syndrome"]}

A number sign (#) is used with this entry because hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) is caused by homozygous or compound heterozygous mutation in the DARS gene (DARS1; 603084) on chromosome 2q21. Description Hypomyelination with brainstem and spinal cord involvement and leg spasticity is an autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation. Affected individuals show delayed motor development and nystagmus; some may have mild mental retardation. Brain MRI shows hypomyelination and white matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord (summary by Taft et al., 2013). Clinical Features Taft et al. (2013) reported 10 patients from 7 unrelated families with severe lower limb spasticity associated with leukoencephalopathy. The families were from various countries, including Pakistan, India, Australia, the U.K., and the U.S., and some were identified from large biorepositories of patients with white matter disorders. Most patients had normal early psychomotor development, but 3 had delayed motor development. Between 4 and 12 months of age, all patients developed progressive motor dysfunction, mainly spasticity affecting the lower limbs more than the upper limbs, as well as axial hypotonia and loss of motor milestones. None achieved independent walking, but some patients were able to walk with support. Other features included nystagmus, hyperreflexia, and extensor plantar responses. Four patients showed mild mental retardation and 3 had pallor of the optic discs. Brain MRI showed extensive white matter abnormalities involving the supratentorial white matter, brainstem, cerebellar peduncles, and dorsal columns and lateral corticospinal tracts of the spinal cord. Taft et al. (2013) noted the phenotypic similarities to leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL; 611105), which is caused by mutation in the DARS2 gene (610956). Inheritance The transmission pattern of HBSL in the families reported by Taft et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 10 patients from 7 unrelated families of various origins with hypomyelination with brainstem and spinal cord involvement and spasticity, Taft et al. (2013) identified homozygous or compound heterozygous mutations in the DARS gene (see, e.g., 603084.0001-603084.0006). The mutations, which were found by exome sequencing, occurred in the 3-prime third of DARS, which corresponds to the C-terminal active-site domain of the enzyme. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Nystagmus \- Pallor of the optic disks (in some patients) NEUROLOGIC Central Nervous System \- Delayed motor development \- Mental retardation, mild (in some patients) \- Spasticity, lower limbs greater than upper limbs \- Hyperreflexia \- Extensor plantar responses \- Independent walking never achieved \- Axial hypotonia \- Leukoencephalopathy \- White matter lesions in the supratentorial white matter, brainstem, cerebellum, and spinal cord \- Hypomyelination \- Thinning of the corpus callosum MISCELLANEOUS \- Onset in first year of life \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the aspartyl-tRNA synthetase 1 gene (DARS1, 603084.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

HYPOMYELINATION WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LEG SPASTICITY

c3809008

omim

https://www.omim.org/entry/615281

{"omim": ["615281"], "orphanet": ["363412"], "synonyms": ["ASPARTYL-tRNA SYNTHETASE DEFICIENCY", "HBSL", "Alternative titles"]}

Peroneal nerve paralysis Other namesPeroneal nerve palsy, Zenker’s paralysis Location of peroneal nerve on foot SpecialtyNeurology Peroneal nerve paralysis is a paralysis on common fibular nerve that affects patient’s ability to lift the foot at the ankle. The condition was named after Friedrich Albert von Zenker. Peroneal nerve paralysis usually leads to neuromuscular disorder, peroneal nerve injury, or foot drop which can be symptoms of more serious disorders such as nerve compression. The origin of peroneal nerve palsy has been reported to be associated with musculoskeletal injury or isolated nerve traction and compression. Also it has been reported to be mass lesions and metabolic syndromes. Peroneal nerve is most commonly interrupted at the knee and possibly at the joint of hip and ankle. Most studies reported that about 30% of peroneal nerve palsy is followed from knee dislocations.[1] Peroneal nerve injury occurs when the knee is exposed to various stress. It occurs when the posterolateral corner structure of knee is injured. Relatively tethered location around fibular head, tenuous vascular supply and epineural connective tissues are possible factors that cause damage on the common peroneal nerve. Treatment options for nerve palsy include both operative and non-operative techniques. Initial treatment includes physical therapy and ankle-foot orthosis. Physical therapy mainly focuses on preventing deformation by stretching the posterior ankle capsule. A special brace or splint worn inside the shoe (called an Ankle Foot Orthosis) holds the foot in the best position for walking. Orthosis stretches posterior ankle structures. Physical therapy can help patients to learn how to walk with a foot drop.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Electromyography * 3.2 Nerve conduction velocity * 3.3 MRI * 4 Prevention * 5 Treatments * 5.1 Tendon transfer * 5.2 Tendon graft * 5.3 Arthroplasty * 6 History * 7 See also * 8 References ## Signs and symptoms[edit] Play media Slapping gait makes a slapping noise at the joint of an ankle. Signs and symptoms of peroneal nerve palsy are related to mostly lower legs and foot which are the following:[3] * Decreased sensation, numbness, or tingling in the top of the foot or the outer part of the upper or lower leg * Foot drops (unable to hold the foot straight across) * Toes drag while walking * Weakness of the ankles or feet * Prickling sensation * Pain in shin * Pins and needles sensation * Slapping gait (walking pattern in which each step makes a slapping noise) Patients may need pain relievers to control pain. Other medications that are used to reduce pain include gabapentin, carbamazepine, or tricyclic antidepressants such as amitriptyline. Whenever if possible, patients need to avoid or limit the use of medication to reduce the risk of side effects. If the pain is severe, a pain specialist can help patients to explore all options to relieve the pain. Physical therapy exercises may help patients to maintain muscle strength. Also, orthopedic devices may improve patient's ability to walk and prevent contractures. Orthopedic devices may include braces, splints, orthopedic shoes, or other equipment. Vocational counseling, occupational therapy, or similar programs may help patients to maximize their mobility and independence. ## Causes[edit] Causing factors of peroneal nerve palsy are such as musculoskeletal or peroneal nerve injuries. Usually paralysis occurs at the outside of the leg and the top of the foot. Palsy causes decrease of muscle strength to lift the foot, twist ankle outside, and move toes around. Major cause of palsy is due to dislocation of knee. Other possible causing factors are metabolic dysfunction of lower part of knee or disorientation of hip or pelvis. Damages on peroneal nerves destroy the myelin sheath that covers the axon or the whole nerve cell. There might be a loss of feeling, muscle control, muscle tone, and eventual loss of muscle mass because the nerves aren't stimulating the muscles after they are damaged. Dysfunction of a single nerve such as the common peroneal nerve is called a mononeuropathy. Mononeuropathy means the nerve damage is occurred in one area. However, certain conditions may also cause single nerve injuries.[4] Common causes of damage to the peroneal nerve include the following: * Traumatic injury on the knee * Fracture of the fibula * Using a tight plaster cast (or other long-term constriction) of the lower leg * Crossing the legs regularly * Regularly wearing high boots * Pressure to the knee from positions during deep sleep or coma * Long period of resting on bed * Broken leg bone[5] Common peroneal nerve injury is more common in people: * Who are very thin (for example, from anorexia nervosa) * Who have conditions such as diabetic neuropathy or polyarteritis nodosa * Who are exposed to certain toxins that can damage the common peroneal nerve Prolonged pressure on nerve may occur because of: * Sitting position * Blood clots, tumors * Casts on lower leg due to tightness[6] ## Diagnosis[edit] For partial nerve palsy, more than 80% of patients will recover completely. For complete nerve palsy, less than 40% of patients will have complete recovery. Peroneal nerve in continuity arises from defined cause will be recovered better than those arise from unknown causes.[7] Examinations are required for following reasons: * Considering lumbar radiculopathy during the examination * Possibility of foot drop * Sensory loss that may be difficult to determine because of variable and small autonomous zone of sensation * Tinel's sign over the fibular neck that can help localize the site of nerve compression * Checking for direct compression that reproduces nerve symptoms ### Electromyography[edit] Electromyography is used to observe peroneal nerve palsy within one month of injuries. And if it is partial peroneal nerve palsy, patients have higher chance to recover fully from the palsy. More than 70 to 80 percent of patients with partial paralysis recovered completely, but those with complete paralysis have chances less than 30 percent to recover completely. If the symptom does not get any better in few months, surgery is required to decompress the nerve compression.[8] ### Nerve conduction velocity[edit] Nerve conduction velocity is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factors, including age, sex, and various medical conditions. Studies allow for better diagnoses of various neuropathies, especially demyelinating conditions as these conditions result in reduced or non-existent conduction velocities. To perform nerve conduction velocity, surface electrodes are placed onto the skin over nerves at various locations. Each patch sends electrical impulses which stimulate the nerve. Resulting electrical activity of nerve is recorded by the other electrodes. The distance between electrodes and the time it takes for electrical impulses to travel between electrodes are used to determine the velocity of the nerve signals.[9] Image of brain MRI. ### MRI[edit] An MRI (magnetic resonance imaging) scan is an imaging test that uses powerful magnets and radio waves to create pictures of the body. It does not use radiation. Single MRI images are called slices. The images can be stored on a computer or printed on film. One exam produces dozens or sometimes hundreds of images. To locate nerve palsy, MRI is used by physicians to detect the position and location of damaged peroneal nerve.[10] ## Prevention[edit] Avoid putting long-term pressure on the back or side of the knee. Treat injuries to the leg or knee right away. If a cast, splint, dressing, or other pressure on the lower leg causes a tight feeling or numbness, call the health care provider.[11] * Avoid crossing legs * Move around actively and frequently * Wear knee protections if working on knee * Alert physician if feeling numbness on leg when casted ## Treatments[edit] Precise knowledge about the length and exact localization of a damaged nerve segment is essential for surgical intervention. On one hand, certain preoperative information about the overall state of an injured nerve (state of the neural and perineural tissue) is important because exploratory inspection of a nerve itself may lead to additional inadvertent damage. If, on the other hand, the surgeon, during genicular ligament reconstruction, inspects a nerve at the site of most probable injury only (limited neurolysis), he or she may sometimes by chance expose an unaffected section of a nerve. Because of the mechanism of nerve injury during traction, however, a more proximal or distal segment of the nerve may be severely damaged. A limited nerve inspection without preoperative knowledge about the site of nerve injury may thus give the false impression of an unimpaired nerve and wrongly lead to conservative treatment of the nerve lesion. If no neurologic improvement is shown after 2–3 months from injuries, then operative decompression is indicated. Surgical operations such as grafting and tendon transfer are necessarily required.[12] ### Tendon transfer[edit] Many different conditions can be treated by tendon transfer surgery. Tendon transfer surgery is necessary when a certain muscle function is lost because of a nerve injury. If a nerve is injured and cannot be repaired, then the nerve no longer sends signals to certain muscles. Those muscles are paralyzed and their muscle function is lost. Tendon transfer surgery can be used to attempt to replace that function. Common nerve injuries that are treated with tendon transfer surgery are spinal cord, radial nerve, ulnar nerve, or median nerve injury. Tendon transfers have higher chance to treat nerve palsy, and such transfers include posterior, anterior, and anteroposterior tibial tendon transfer. Peroneal nerve and its nerve branches need to be fixed from adherence to proximal fibula, which proximal fibula is about 3~5 cm.[13] ### Tendon graft[edit] Grafting is a surgical procedure to move tissue from one site to another on the body, or from another person, without bringing its own blood supply with it. Instead, a new blood supply grows in after it is placed. A similar technique where tissue is transferred with the blood supply intact is called a flap. In some instances a grafting can be an artificially manufactured device. Examples of this are a tube to carry blood flow across a defect or from an artery to a vein for use in hemodialysis.[14] ### Arthroplasty[edit] Arthroplasty on knee has been broadly used to treat knee and musculoskeletal joint dislocation. It is an elective procedure that is done to relieve pain and restore function to the joint after damage by arthritis or some other type of trauma. However, there has been series of reports arthroplasty worsens condition of peroneal nerve, causing paralysis. Other forms of arthroplasty include resection (al) arthroplasty, resurfacing arthroplasty, mold arthroplasty, cup arthroplasty, silicone replacement arthroplasty, etc.[15] ## History[edit] Friedrich Albert von Zenker Friedrich Albert von Zenker (1825–1898) was a German pathologist and physician, celebrated for his discovery of trichinosis. He was born in Dresden and was educated in Leipzig and Heidelberg. He worked in the city hospital of Dresden in 1851 and became a professor of pathological anatomy and general pathology in the surgico-medical academy of the city. In 1862 he became a professor of pathological anatomy and pharmacology at Erlangen. Three years later he assumed with Ziemssen the editorship of the Deutsches Archiv für klinische Medizin. In 1895 he retired from active service. His important discovery of the danger of trichine dates from 1860. In that year he published "Über die Trichinenkrankheit des Menschen" ("On the trichine-illness of humans", in volume XVIII of Virchow's Archiv). Zenker also found Zenker's degeneration and Zenker's diverticulum.[16] ## See also[edit] * Zenker's diverticulum * Zenker's degeneration ## References[edit] 1. ^ Levy, Bruce A.; Giuseffi, Steven A.; Bishop, Allen T.; Shin, Alexander Y.; Dahm, Diane L.; Stuart, Michael J. (2010). "Surgical treatment of peroneal nerve palsy after knee dislocation". Knee Surgery, Sports Traumatology, Arthroscopy. 18 (11): 1583–6. doi:10.1007/s00167-010-1204-3. PMID 20640404. 2. ^ Werner, B. C.; F. W. Gwathmey; M. L. Lyons; M. D. Miller (2013). "Peroneal Nerve Injury after Multiligament Knee Injury: a 12 Year Experience with a Focus on Outcomes after Posterior Tibial Tendon Transfer". Orthopaedic Journal of Sports Medicine. 1 (4 Suppl): 2325967113S0008. doi:10.1177/2325967113S00080. ISSN 2325-9671. PMC 4589012. 3. ^ Eleftheriou, Kyriacos I.; Sushil Beri; Afshin Alavi; Sally Tennant (2013). "Deep peroneal nerve palsy during growth spurt: a case report". European Journal of Pediatrics. 173 (12): 1603–5. doi:10.1007/s00431-013-2160-y. ISSN 0340-6199. PMID 24061281. 4. ^ Bendszus, M; Reiners, K; Perez, J; Solymosi, L; Koltzenburg, M (2002). "Peroneal nerve palsy caused by thrombosis of crural veins". Neurology. 58 (11): 1675–7. doi:10.1212/WNL.58.11.1675. PMID 12058098. 5. ^ Krych, A. J.; S. Giuseffi; S. A. Kuzma; J. L. Hudgens; M. J. Stuart; B. A. Levy (2013). "Clinical and Functional Outcomes after Multiligament Knee Injury with Associated Peroneal Nerve Palsy: Comparison with a Matched Control Group at 2-18 Years". Orthopaedic Journal of Sports Medicine. 1 (4 Suppl): 2325967113S0008. doi:10.1177/2325967113S00082. ISSN 2325-9671. PMC 4588998. 6. ^ http://health.nytimes.com/health/guides/disease/common-peroneal-nerve-dysfunction/overview.html[full citation needed] 7. ^ http://www.wheelessonline.com/ortho/12636[full citation needed] 8. ^ Ward, Joseph P.; Lynda J.-S. Yang, Andrew G. Urquhart (2013). "Surgical Decompression Improves Symptoms of Late Peroneal Nerve Dysfunction After TKA". Orthopedics. 36 (4): e515–e519. doi:10.3928/01477447-20130327-33. ISSN 0147-7447. PMID 23590795. 9. ^ Garg, Ruchika (2012). "Footdrop in the Farmers in Punjab: A Retrospective Electrodiagnostic Study". Journal of Clinical and Diagnostic Research. 6 (10): 1653–1657. doi:10.7860/JCDR/2012/4829.2648. ISSN 2249-782X. PMC 3552197. PMID 23373021. 10. ^ http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/peripheral_nerve_surgery/conditions/foot_drop_injury.html[full citation needed][permanent dead link] 11. ^ Jahangiri, F; R Wimberly; S Mcclure; L Blakemore (2006). "P27.3 Multimodality neurophysiological monitoring during tibial/fibular osteotomies for preventing peripheral nerve injuries". Clinical Neurophysiology. 117: 114–115. doi:10.1016/j.clinph.2006.06.457. ISSN 1388-2457. 12. ^ Mont, MA; Dellon, AL; Chen, F; Hungerford, MW; Krackow, KA; Hungerford, DS (1996). "The operative treatment of peroneal nerve palsy". The Journal of Bone and Joint Surgery. American Volume. 78 (6): 863–9. doi:10.2106/00004623-199606000-00009. PMID 8666604. 13. ^ Titolo, Paolo; Bernardino Panero; Davide Ciclamini; Bruno Battiston; Pierluigi Tos (2013). "Letter to the Editor: New Tendon Transfer for Correction of Drop-foot in Common Peroneal Nerve Palsy". Clinical Orthopaedics and Related Research. 471 (10): 3382. doi:10.1007/s11999-013-3175-4. ISSN 0009-921X. PMC 3773138. PMID 23907607. 14. ^ Wagenaar, Frank-Christiaan B.M.; Louwerens, Jan Willem K. (2007). "Posterior Tibial Tendon Transfer: Results of Fixation to the Dorsiflexors Proximal to the Ankle Joint". Foot & Ankle International. 28 (11): 1128–42. doi:10.3113/FAI.2007.1128. PMID 18021581. 15. ^ Deshmukh, Ajit J.; Bozena Kuczynski; Giles R. Scuderi (2013). "Delayed peroneal nerve palsy after total knee arthroplasty—A rare complication of tibial osteolysis". The Knee. 21 (2): 624–7. doi:10.1016/j.knee.2013.10.015. ISSN 0968-0160. PMID 24262809. 16. ^ "Whonamedit - Friedrich Albert von Zenker". whonamedit.com. 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Peroneal nerve paralysis

c0270810

wikipedia

https://en.wikipedia.org/wiki/Peroneal_nerve_paralysis

{"mesh": ["D020427"], "wikidata": ["Q3895159"]}

Herpes gladiatorum is one of the most infectious of herpes-caused diseases, and is transmissible by skin-to-skin contact. The disease was first described in the 1960s in the New England Journal of Medicine. It is caused by contagious infection with human herpes simplex virus type 1 (HSV-1),[1] which more commonly causes oral herpes (cold sores). Another strain, HSV-2 usually causes genital herpes, although the strains are very similar and either can cause herpes in any location. While the disease is commonly passed through normal human contact, it is strongly associated with contact sports—outbreaks in sporting clubs being relatively common.[2] Other names for the disease are herpes rugbiorum or "scrumpox"[2] (after rugby football), "wrestler's herpes" or "mat pox" (after wrestling). In one of the largest outbreaks ever among high-school wrestlers at a four-week intensive training camp, HSV was identified in 60 of 175 wrestlers. Lesions were on the head in 73 percent of the wrestlers, the extremities in 42 percent, and the trunk in 28 percent.[3] Physical symptoms sometimes recur in the skin.[4] Previous adolescent HSV-1 seroconversion would preclude most herpes gladiatorum, but being that stress and trauma are recognized triggers, such a person would be likely to infect others. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 3.1 Similar infections * 4 Prevention * 5 Treatment * 6 See also * 7 References ## Signs and symptoms[edit] Herpes gladiatorum is characterized by a rash with clusters of sometimes painful fluid-filled blisters, often on the neck, chest, face, stomach, and legs. The infection is often accompanied by lymphadenopathy (enlargement of the lymph nodes), fever, sore throat, and headache.[5] Often, the accompanying symptoms are much more of an inconvenience than the actual skin blisters and rash. Each blister contains infectious virus particles (virions). Close contact, particularly abrasive contact as found in contact sports, causes the infected blisters to burst and pass the infection along. Autoinoculation (self-infection) can occur through self-contact, leading to infection at multiple sites on the body.[5] Herpes gladiatorum symptoms may last up to a few weeks, and if they occur during the first outbreak, they can be more pronounced. In recurrences of the ailment, symptoms are milder, even if lesions still tend to occur. With recurrent infections scabs may form at 3 days yet the lesions are still considered infectious up until 6.4 days after starting oral antiviral medications.[6] Healing takes place without leaving scars. It is possible that the condition evolves asymptomatically and sores are never present. ## Causes[edit] Herpes gladiatorum is a skin infection primarily caused by the herpes simplex virus. The virus infects the cells in the epidermal layer of the skin. The initial viral replication occurs at the entry site in the skin or mucous membrane.[7] The infections caused by a HSV Type 1 virus may be primary or recurrent.[8] Studies show that even though most of the individuals who are exposed to the virus get infected, only 10% from them will develop sores as well. These types of sores appear within two to twenty days after exposure and usually do not last longer than ten days. Primary infections usually heal completely without leaving scars but the virus that caused the infection in the first place remains in the body in a latent state. This is the reason why most of the people experience recurrences even after the condition is taken care of. The virus moves to the nerve cells from where it can reactivate. Once the condition has recurred, it is normally a mild infection. The infection may be triggered by several external factors such as sun exposure or trauma. Infection with either type of the HSV viruses occurs in the following way: First, the virus comes in contact with damaged skin, and then it goes to the nuclei of the cells and reproduces or replicates.[9] The blisters and ulcers formed on the skin are a result of the destruction of infected cells. In its latent form, the virus does not reproduce or replicate until recurrence is triggered by different factors. ## Pathophysiology[edit] Herpes gladiatorum is transmitted by direct contact with skin lesions caused by a herpes simplex virus.[1] This is the main reason why the condition is often found in wrestlers. It is believed that the virus may be transmitted through infected wrestlers' mats, but this is still subject of research since the virus cannot live long enough outside the body in order to be able to cause an infection. Direct contact with an infected person or infected secretions is undoubtedly the main way in which this virus may be transmitted. It is also believed that wearing abrasive clothing may increase the chances to get infected with this type of virus. Shirts made of polyester and cotton may cause frictions that lead to small breaks in the skin which makes it easier to contract the infection. Studies in which athletes were wearing 100% cotton shirts showed a decrease in the number of herpes gladiatorum cases.[10] The spread is facilitated when a sore is present but it can happen in its absence as well. The patients may know that the virus is present on the skin when they experience the so-called "prodromal symptoms". These include itching or tingling on the skin, right before the blisters or lesions appear. The virus may spread since the first symptoms appear until lesions are completely healed. The incubation period is situated between 3 and 14 days. This means that a person will experience the symptoms within 14 days after he or she contracted the infection. This type of virus may be transmitted even if the symptoms are not yet present. Some individuals can have very mild symptoms that may not be taken as herpes symptoms and the patient may not recognize them. The asymptomatic transmission occurs when the infection is spread between outbreaks.[11] ### Similar infections[edit] Herpes gladiatorum is only caused by the herpes simplex virus. Shingles, also manifesting as skin rashes with blisters, is caused by a different virus, herpes zoster. Other agents may cause skin infections, for example ringworm is primarily due to the fungal dermatophyte, T. tonsurans. Impetigo, cellulitis, folliculitis and carbuncles are usually due to Staphylococcus aureus or Beta-hemolytic streptococcus bacteria. These less common forms can be potentially more serious.[2] Anti-viral treatments will not have an effect in non-viral cases. Bacterial infections must be treated with antibiotics and fungal infections with anti-fungal medication.[2] ## Prevention[edit] Key measures to prevent outbreaks of the disease are maintaining hygiene standards and using screening to exclude persons with suspicious infections from engaging in contact sports. A skin check performed before practice or competition takes place can identify individuals who should be evaluated, and if necessary treated by a healthcare professional.[5] In certain situations, i.e. participating in wrestling camps, consider placing participants on valacyclovir 1GM daily for the duration of camp. 10-year study has shown 89.5% reduction in outbreaks and probable prevention of contracting the virus. Medication must be started 5 days before participation to ensure proper concentrations exist.[12] ## Treatment[edit] Herpes outbreaks should be treated with antiviral medications like Acyclovir, Valacyclovir, or Famcyclovir, each of which is available in tablet form.[2] Oral antiviral medication is often used as a prophylactic to suppress or prevent outbreaks from occurring.[13] The recommended dosage for suppression therapy for recurrent outbreaks is 1,000 mg of valacyclovir once a day or 400 mg Acyclovir taken twice a day. In addition to preventing outbreaks, these medications greatly reduce the chance of infecting someone while the patient is not having an outbreak. Often, people have regular outbreaks of anywhere from 1 to 10 times per year, but stress (because the virus lies next to the nerve cells), or a weakened immune system due to a temporary or permanent illness can also spark outbreaks. Some people become infected but fail to ever have a single outbreak, although they remain carriers of the virus and can pass the disease on to an uninfected person through asymptomatic shedding (when the virus is active on the skin but rashes or blisters do not appear). The use of antiviral medications has been shown to be effective in preventing acquisition of the herpes virus.[14] Specific usage of these agents focus on wrestling camps where intense contact between individuals occur on a daily basis over several weeks. They have also been used for large outbreaks during seasonal competition, but further research needs to be performed to verify efficacy. ## See also[edit] * Herpes simplex * List of cutaneous conditions ## References[edit] 1. ^ a b Likness, LP (June 2011). "Common dermatologic infections in athletes and return-to-play guidelines". The Journal of the American Osteopathic Association. 111 (6): 373–379. doi:10.7556/jaoa.2011.111.6.373. PMID 21771922. 2. ^ a b c d e Sharp JCM (1994-06-24). "ABC of Sports Medicine: Infections in sport" (Education and Debate). BMJ. 308 (6945): 1702–1706. doi:10.1136/bmj.308.6945.1702. PMC 2540619. PMID 8025471. 3. ^ Belongia EA, Goodman JL, Holland EJ, et al. (September 1991). "An outbreak of herpes gladiatorum at a high-school wrestling camp". N. Engl. J. Med. 325 (13): 906–10. doi:10.1056/NEJM199109263251302. PMID 1652687. 4. ^ Fatahzadeh M, Schwartz RA (November 2007). "Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management". J. Am. Acad. Dermatol. 57 (5): 737–63, quiz 764–6. doi:10.1016/j.jaad.2007.06.027. PMID 17939933. 5. ^ a b c Centers for Disease Control (CDC) (1990-02-09). "Epidemiologic Notes and Reports Herpes Gladiatorum at a High School Wrestling Camp—Minnesota". MMWR. CDC. 39 (5): 69–71. PMID 2105440. 6. ^ Anderson, BJ (September 2005). "Valacyclovir to expedite the clearance of recurrent herpes gladiatorum". Clinical Journal of Sport Medicine. 15 (5): 364–6. doi:10.1097/01.jsm.0000181468.44397.ce. PMID 16162997. 7. ^ eMedicine Portal. "Herpes Simplex details" 2010-02-10. 8. ^ American academy of dermatology. "Herpes Simplex explained"[permanent dead link] 2010-02-10. 9. ^ Herpes Simplex Virus infection and recurrence About health online portal. Retrieved on 2010-02-10 10. ^ Ramin, Kordi (2009). Combat sports medicine. ISBN 978-1-84800-353-8. 11. ^ Herpes detailed analysis eMedicine. 2010-02-10 12. ^ Anderson BJ, McGuire D, Reed, M, Foster M, Ortiz D. Prophylactic Valacyclovir to Prevent Outbreaks of Primary Herpes Gladiatorum at a 28-day camp: a 10-year review.Clin J Sports Med. 2016. 26:4: 272–8. 13. ^ Anderson, BJ (April 1999). "The effectiveness of valacyclovir in preventing reactivation of herpes gladiatorum in wrestlers". Clinical Journal of Sport Medicine. 9 (2): 86–90. doi:10.1097/00042752-199904000-00008. PMID 10442623. 14. ^ Anderson, BJ (February 2006). "Prophylactic valacyclovir to prevent outbreaks of primary herpes gladiatorum at a 28-day wrestling camp". Japanese Journal of Infectious Diseases. 59 (1): 6–9. PMID 16495626. * v * t * e Skin infections, symptoms and signs related to viruses DNA virus Herpesviridae Alpha HSV * Herpes simplex * Herpetic whitlow * Herpes gladiatorum * Herpes simplex keratitis * Herpetic sycosis * Neonatal herpes simplex * Herpes genitalis * Herpes labialis * Eczema herpeticum * Herpetiform esophagitis Herpes B virus * B virus infection VZV * Chickenpox * Herpes zoster * Herpes zoster oticus * Ophthalmic zoster * Disseminated herpes zoster * Zoster-associated pain * Modified varicella-like syndrome Beta * Human herpesvirus 6/Roseolovirus * Exanthema subitum * Roseola vaccinia * Cytomegalic inclusion disease Gamma * KSHV * Kaposi's sarcoma Poxviridae Ortho * Variola * Smallpox * Alastrim * MoxV * Monkeypox * CPXV * Cowpox * VV * Vaccinia * Generalized vaccinia * Eczema vaccinatum * Progressive vaccinia * Buffalopox Para * Farmyard pox: Milker's nodule * Bovine papular stomatitis * Pseudocowpox * Orf * Sealpox Other * Yatapoxvirus: Tanapox * Yaba monkey tumor virus * MCV * Molluscum contagiosum Papillomaviridae HPV * Wart/plantar wart * Heck's disease * Genital wart * giant * Laryngeal papillomatosis * Butcher's wart * Bowenoid papulosis * Epidermodysplasia verruciformis * Verruca plana * Pigmented wart * Verrucae palmares et plantares * BPV * Equine sarcoid Parvoviridae * Parvovirus B19 * Erythema infectiosum * Reticulocytopenia * Papular purpuric gloves and socks syndrome Polyomaviridae * Merkel cell polyomavirus * Merkel cell carcinoma RNA virus Paramyxoviridae * MeV * Measles Togaviridae * Rubella virus * Rubella * Congenital rubella syndrome ("German measles" ) * Alphavirus infection * Chikungunya fever Picornaviridae * CAV * Hand, foot, and mouth disease * Herpangina * FMDV * Foot-and-mouth disease * Boston exanthem disease Ungrouped * Asymmetric periflexural exanthem of childhood * Post-vaccination follicular eruption * Lipschütz ulcer * Eruptive pseudoangiomatosis * Viral-associated trichodysplasia * Gianotti–Crosti syndrome *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Herpes gladiatorum

c2030860

wikipedia

https://en.wikipedia.org/wiki/Herpes_gladiatorum

{"wikidata": ["Q17155680"]}

Antineoplastic resistance, often used interchangeably with chemotherapy resistance, is the resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies.[1] In some cases, cancers can evolve resistance to multiple drugs, called multiple drug resistance. There are two general causes of antineoplastic therapy failure: Inherent genetic characteristics, giving cancer cells their resistance and acquired resistance after drug exposure, which is rooted in the concept of cancer cell heterogeneity.[1] Characteristics of resistant cells include altered membrane transport, enhanced DNA repair, apoptotic pathway defects, alteration of target molecules, protein and pathway mechanisms, such as enzymatic deactivation.[1] Since cancer is a genetic disease, two genomic events underlie acquired drug resistance: Genome alterations (e.g. gene amplification and deletion) and epigenetic modifications. Cancer cells are constantly using a variety of tools, involving genes, proteins, and altered pathways, to ensure their survival against antineoplastic drugs. ## Contents * 1 Definition * 2 Cancer cell heterogeneity * 3 Acquired resistance * 3.1 Genetic causes * 3.1.1 Genome alterations * 3.1.2 Epigenetic mechanisms * 3.2 Cancer cell mechanisms * 3.2.1 Altered membrane transport * 3.2.2 Enhanced DNA repair * 3.2.3 Apoptotic pathway defects * 3.2.4 Altered target molecules * 3.3 Altered metabolism * 4 Genetic markers for drug sensitivity and resistance * 5 Genetic approaches to overcome drug resistance * 6 References ## Definition[edit] Antineoplastic resistance, synonymous with chemotherapy resistance, is the ability of cancer cells to survive and grow despite different anti-cancer therapies, i.e. their multiple drug resistance. There are two general causes of antineoplastic therapy failure:[2] Inherent resistance, such as genetic characteristics, giving cancer cells their resistance from the beginning, which is rooted in the concept of cancer cell heterogeneity and acquired resistance after drug exposure.[2] ## Cancer cell heterogeneity[edit] Cancer cell heterogeneity, or tumour heterogeneity, is the idea that tumours are made up of different populations of cancer cells that are morphologically, phenotypically and functionally different.[3] Certain populations of cancer cells may possess inherent characteristics, such as genetic mutations and/or epigenetic changes, that confer drug resistance. Antineoplastic drugs kill susceptible sub-populations and the tumour mass may shrink as an initial response to the drug, resistant cancer cells will survive treatment, be selected and then propagate, eventually causing a cancer relapse. Cancer cell heterogeneity can cause disease progression when molecularly targeted therapy, fails to kill those tumor cells which do not express the marker, then divide and mutate further, creating a new heterogeneous tumour. In breast cancer models of the mouse the immune microenvironment affects susceptibility to neoadjuvant chemotherapy. In breast cancer, particularly in the triple-negative subtype, immune checkpoint blockade has been used successfully in metastatic cases and neoadjuvant therapy.[4] ## Acquired resistance[edit] Since cancer is a genetic disease,[5] two genomic events underlie these mechanisms of acquired drug resistance: Genome alterations (e.g. gene amplification and deletion) and epigenetic modifications. ### Genetic causes[edit] #### Genome alterations[edit] Chromosomal rearrangement due to genome instability can cause gene amplification and deletion. Gene amplification is the increase in copy number of a region of a chromosome.[6] which occur frequently in solid tumors, and can contribute to tumor evolution through altered gene expression.[6] Hamster cell research in 1993 showed that amplifications in the DHFR gene involved in DNA synthesis began with chromosome break in below the gene, and subsequent cycles of bridge-breakage-fusion formations result in large intrachromosomal repeats.[7] The over amplification of oncogenes can occur in response to chemotherapy, thought to be the underlying mechanism in several classes of resistance.[6] For example, DHFR amplification occurs in response to methotrexate,[8] TYMS (involved in DNA synthesis) amplification occurs in response to 5-fluorouracil,[9] and BCR-ABL amplification occurs in response to imatinib mesylate.[10] Determining areas of gene amplification in cells from cancer patients has huge clinical implications. Gene deletion is the opposite of gene amplification, where a region of a chromosome is lost an drug resistance occurs by losing tumor suppressor genes such as TP53.[2] Genomic instability can occur when the replication fork is disturbed or stalled in its migration. This can occur with replication fork barriers, proteins such as PTIP, CHD4 and PARP1, which are normally cleared by the cell´s DNA damage sensors, surveyors, and responders BRCA1 and BRCA2.[11] #### Epigenetic mechanisms[edit] Epigenetic modifications in antineoplastic drug resistance play a major role in cancer development and drug resistance as they contribute to the regulation of gene expression.[12] Two main types of epigenetic control are DNA methylation and histone methylation/acetylation. DNA methylation is the process of adding methyl groups to DNA, usually in the upstream promoter regions, which stops DNA transcription at the region and effectively silences individual genes. Histone modifications, such as deacetylation, alters chromatin formation and silence large chromosomal regions. In cancer cells, where normal regulation of gene expression breaks down, the oncogenes are activated via hypomethylation and tumor suppressors are silenced via hypermethylation. Similarly, in drug resistance development, it has been suggested that epigenetic modifications can result in the activation and overexpression of pro-drug resistance genes.[12] Studies on cancer cell lines have shown that hypomethylation (loss of methylation) of the MDR1 gene promoter caused overexpression and the multidrug resistance.[13] In a methotrexate resistant breast cancer cell lines without drug uptake and folate carrier expression, giving DAC, a DNA methylation inhibitor, improved drug uptake and folate carrier expression.[14] Acquired resistance to the alkylating drug fotemustine in melanoma cell showed high MGMT activity related to the hypermethylation of the MGMT gene exons.[15] In Imatinib resistant cell lines, silencing of the SOCS-3 gene via methylation has been shown to cause STAT3 protein activation, which caused uncontrolled proliferation.[16] ### Cancer cell mechanisms[edit] Cancer cells can become resistant to multiple drugs by altered membrane transport, enhanced DNA repair, apoptotic pathway defects, alteration of target molecules, protein and pathway mechanisms, such as enzymatic deactivation.[12] #### Altered membrane transport[edit] An overview of antineoplastic resistance mechanisms, and examples of the major genes involved. Blue boxes indicate cancer cell proliferation mechanisms; green boxes indicate therapeutic interventions; red boxes indicate resistance mechanisms. Many classes of antineoplastic drugs act on intracellular components and pathways, like DNA, nuclear components, meaning that they need to enter the cancer cells. The p-glycoprotein (P-gp), or the multiple drug resistance protein, is a phosphorylated and glycosylated membrane transporter that can shuttle drugs out of the cell, thereby decreasing or ablating drug efficacy. This transporter protein is encoded by the MDR1 gene and is also called the ATP-binding cassette (ABC) protein. MDR1 has promiscuous substrate specificity, allowing it to transport many structurally diverse compounds across the cell membrane, mainly hydrophobic compounds. Studies have found that the MDR1 gene can be activated and overexpressed in response to pharmaceutical drugs, thus forming the basis for resistance to many drugs.[2] Overexpression of the MDR1 gene in cancer cells is used to keep intracellular levels of antineoplastic drugs below cell-killing levels. For example, the antibiotic rifampicin has been found to induce MDR1 expression. Experiments in different drug resistant cell lines and patient DNA revealed gene rearrangements which had initiated the activation or overexpression of MDR1.[17] A C3435T polymorphism in exon 226 of MDR1 has also been strongly correlated with p-glycoprotein activities.[18] MDR1 is activated through NF-κB, a protein complex which acts as a transcription factor.[19][20][21][22] In the rat, an NF-κB binding site is adjacent to the mdr1b gene,[23] NF-κB can be active in tumour cells because its mutated NF-κB gene or its inhibitory IκB gene mutated under chemotherapy. In colorectal cancer cells, inhibition of NF-κB or MDR1 caused increased apoptosis in response to a chemotherapeutic agent.[19] #### Enhanced DNA repair[edit] Enhanced DNA repair plays an important role in the ability for cancer cells to overcome drug-induced DNA damages. Platinum-based chemotherapies, such as cisplatin, target tumour cells by cross-linking their DNA strands, causing mutation and damage.[2] Such damage will trigger programmed cell death (e.g. apoptosis) in cancer cells. Cisplatin resistance occurs when cancer cells develop an enhanced ability to reverse such damage by removing the cisplatin from DNA and repairing any damage done.[2][12] The cisplatin-resistant cells upregulate expression of the excision repair cross-complementing (ERCC1) gene and protein.[2] Some chemotherapies are alkylating agents meaning they attach an alkyl group to DNA to stop it from being read. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme which removes alkyl groups from DNA. MGMT expression is upregulated in many cancer cells, which protects them from alkylating agents.[12] Increased MGMT expression has been found in colon cancer, lung cancer, non-Hodgkin’s lymphoma, breast cancer, gliomas, myeloma and pancreatic cancer.[24] #### Apoptotic pathway defects[edit] TP53 is a tumor suppressor gene encoding the p53 protein, which responds to DNA damage either by DNA repair, cell cycle arrest, or apoptosis. Losing TP53 via gene deletion can allow cells to continuously replicate despite DNA damage. The tolerance of DNA damage can grant cancer cells a method of resistance to those drugs which normally induce apoptosis through DNA damage.[2][12] Other genes involved in the apoptotic pathway related drug resistance include h-ras and bcl-2/bax.[25] Oncogenic h-ras has been found to increase expression of ERCC1, resulting in enhanced DNA repair (see above).[26] Inhibition of h-ras was found to increase cisplatin sensitivity in glioblastoma cells.[27] Upregulated expression of Bcl-2 in leukemic cells (non-Hodgkin’s lymphoma) resulted in decreased levels of apoptosis in response to chemotherapeutic agents, as Bcl-2 is a pro-survival oncogene.[28] #### Altered target molecules[edit] During targeted therapy, oftentimes the target has modified itself and decreased its expression to the point that therapy is no longer effective. One example of this is the loss of estrogen receptor (ER) and progesterone receptor (PR) upon anti-estrogen treatment of breast cancer.[29] Tumors with loss of ER and PR no longer respond to tamoxifen or other anti-estrogen treatments, and while cancer cells remain somewhat responsive to estrogen synthesis inhibitors, they eventually become unresponsive to endocrine manipulation and no longer dependent on estrogen for growth.[29] Another line of therapeutics used for treating breast cancer is targeting of kinases like human epidermal growth factor receptor 2 (HER2) from the EGFR family. Mutations often occur in the HER2 gene upon treatment with an inhibitor, with about 50% of patients with lung cancer found to have an EGFR-T790M gatekeeper mutation.[12] Treatment of chronic myeloid leukemia (CML) involves a tyrosine kinase inhibitor that targets the BCR/ABL fusion gene called imatinib. In some people resistant to Imatinib, the BCR/ABL gene is reactivated or amplified, or a single point mutation has occurred on the gene. These point mutations enhance autophosphorylation of the BCR-ABL protein, resulting in the stabilization of the ATP-binding site into its active form, which cannot be bound by imatinib for proper drug activation.[30] Topoisomerase is a lucrative target for cancer therapy due to its critical role as an enzyme in DNA replication, and many topoisomerase inhibitors have been made.[31] Resistance can occur when topoisomerase levels are decreased, or when different isoforms of topoisomerase are differentially distributed within the cell. Mutant enzymes have also been reported in patient leukemic cells, as well as mutations in other cancers that confer resistance to topoisomerase inhibitors.[31] ### Altered metabolism[edit] One of the mechanisms of antineoplastic resistance is over-expression of drug-metabolizing enzymes or carrier molecules.[2] By increasing expression of metabolic enzymes, drugs are more rapidly converted to drug conjugates or inactive forms that can then be excreted. For example, increased expression of glutathione promotes drug resistance, as the electrophilic properties of glutathione allow it to react with cytotoxic agents, inactivating them.[32] In some cases, decreased expression or loss of expression of drug-metabolising enzymes confers resistance, as the enzymes are needed to process a drug from an inactive form to an active form. Arabinoside, a commonly used chemotherapy for leukemia and lymphomas, is converted into cytosine arabinoside triphosphate by deoxycytidine kinase. Mutation of deoxycytidine kinase or loss of expression results in resistance to arabinoside.[2] This is a form of enzymatic deactivation. Growth factor expression levels can also promote resistance to antineoplastic therapies.[2] In breast cancer, drug resistant cells were found to express high levels of IL-6, while sensitive cells did not express significant levels of the growth factor. IL-6 activates the CCAAT enhancer-binding protein transcription factors which activate MDR1 gene expression (see Alteration of Membrane Transport).[33] ## Genetic markers for drug sensitivity and resistance[edit] Pharmacogenetics play an increasingly important role in antineoplastic treatment.[34] Rapid sequencing technologies can identify genetic markers for treatment sensitivity and potential resistance. Certain markers are more representative and more likely to be used clinically.[34] When BRCA1 and BRCA2 are missing, as in 5 percent to 10 percent of all breast cancers, a stalled fork remains destabilized and its newly synthesized DNA is degraded. This genomic instability means the cancer cell is actually more sensitive to DNA-damaging chemotherapy drugs.[35] Characteristics of Pharmacogenetic Tests[34] Marker Drug Major Conditions Clinical Implications TYMS 5-Fluorouracil Colorectal, stomach, pancreatic cancer High TYMS may show poor response & less toxicity DPYD 5-Fluorouracil Colorectal, stomach, pancreatic cancer DPD deficiency associated with higher risk of toxicity UGT1A1 Irinotecan Colorectal cancer Decreased UGT1A1 activity may increase risk of toxicity CYP2D6 Tamoxifen Breast cancer Patients with deficient CYP2D6 activity are at greater risks of relapse EGFR Anti-EGFR therapy Colorectal, lung cancer Activation of EGFR pathways enhances tumor growth, progression, & resistance to therapy KRAS Anti-EGFR therapy Colorectal, lung cancer KRAS mutation is associated with resistance to anti-EGFR therapy FCGR3A Rituximab Non-Hodgkin's lymphoma FCRG3A 158Val/Val genotype may be associated with better response BRCA1/BRCA2 Platinum Breast, ovarian cancer BRCA1/2-mutated cancers are more sensitive to DNA damage. Secondary intragenic mutations confer acquired resistance ## Genetic approaches to overcome drug resistance[edit] MDR proteins are known to be drug-resistance genes, and are highly expressed in various cancers. Inhibition of the MDR genes could result in sensitization of cells to therapeutics and a decrease in antineoplastic resistance. Reversin 121 (R121) is a high-affinity peptide for MDR, and use of R121 as a treatment for pancreatic cancer cells results in increased chemosensitivity and decreased proliferation.[36] Aberrant NF-κB expression is found in many cancers, and NF-κB has been found to be involved in resistance to platinum-based chemotherapies, such as cisplatin. NF-κB inhibition by genistein in various cancer cell lines (prostate, breast, lung and pancreas) showed increased growth inhibition and an increase in chemosensitivity, seen as an increase in apoptosis induced by therapeutic agents.[37] However, targeting the NF-κB pathway can be difficult, as there can be many off-target and non-specific effects. Expression of mutated TP53 causes defects in the apoptotic pathway, allowing cancerous cells to avoid death. Re-expression of the wild-type gene in cancer cells in vitro has been shown to inhibit cell proliferation, induce cell cycle arrest and apoptosis.[38] In ovarian cancer, the ATP7B gene encodes for a copper efflux transporter, found to be upregulated in cisplatin-resistant cell lines and tumors. Development of antisense deoxynucleotides against ATP7B mRNA and treatment of an ovarian cancer cell line shows that inhibition of ATP7B increases sensitivity of the cells to cisplatin.[39] ## References[edit] 1. ^ a b c Alfarouk, KO; Stock, CM; Taylor, S; Walsh, M; Muddathir, AK; Verduzco, D; Bashir, AH; Mohammed, OY; Elhassan, GO; Harguindey, S; Reshkin, SJ; Ibrahim, ME; Rauch, C (2015). "Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp". Cancer Cell International. 15: 71. doi:10.1186/s12935-015-0221-1. PMC 4502609. PMID 26180516. 2. ^ a b c d e f g h i j k Luqmani, Y.A. (2005). "Mechanisms of Drug Resistance in Cancer Chemotherapy". Medical Principles and Practice. 14 (1): 35–48. doi:10.1159/000086183. PMID 16103712. 3. ^ Marusyk, Andriy; Polyak, Kornelia (2010-01-01). "Tumor heterogeneity: causes and consequences". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1805 (1): 105–17. doi:10.1016/j.bbcan.2009.11.002. ISSN 0006-3002. PMC 2814927. PMID 19931353. 4. ^ DeMichele A, Yee D, Esserman L (2017). "Mechanisms of Resistance to Neoadjuvant Chemotherapy in Breast Cancer". N Engl J Med. 377 (23): 2287–2289. doi:10.1056/NEJMcibr1711545. PMID 29211674. 5. ^ "The Genetics of Cancer". National Cancer Institute. 22 April 2015. Retrieved 25 February 2016. 6. ^ a b c Albertson, Donna G. (2006-08-01). "Gene amplification in cancer". Trends in Genetics. 22 (8): 447–455. doi:10.1016/j.tig.2006.06.007. ISSN 0168-9525. PMID 16787682. 7. ^ Ma, C.; Martin, S.; Trask, B.; Hamlin, J. L. (1993-04-01). "Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells". Genes & Development. 7 (4): 605–620. doi:10.1101/gad.7.4.605. ISSN 0890-9369. PMID 8458577. 8. ^ Gorlick, Richard; Goker, Erdem; Trippett, Tanya; Waltham, Mark; Banerjee, Debabrata; Bertino, Joseph R. (1996-10-03). "Intrinsic and acquired resistance to methotrexate in acute leukemia". N. Engl. J. Med. 335 (14): 1041–1048. doi:10.1056/NEJM199610033351408. PMID 8793930. 9. ^ Wang, Tian-Li; Diaz, Luis A.; Romans, Katharine; et al. (2004-03-02). "Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients". Proceedings of the National Academy of Sciences of the United States of America. 101 (9): 3089–3094. Bibcode:2004PNAS..101.3089W. doi:10.1073/pnas.0308716101. ISSN 0027-8424. PMC 420348. PMID 14970324. 10. ^ Gorre, M. E.; Mohammed, M.; Ellwood, K.; et al. (2001-08-03). "Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification". Science. 293 (5531): 876–880. doi:10.1126/science.1062538. ISSN 0036-8075. PMID 11423618. 11. ^ Uncovering a new principle in chemotherapy resistance in breast cancer July 20, 2016, NCI Press Office, retrieved 7 December 2017 12. ^ a b c d e f g Housman, Genevieve; Byler, Shannon; Heerboth, Sarah; Lapinska, Karolina; Longacre, Mckenna; Snyder, Nicole; Sarkar, Sibaji (2014-09-05). "Drug Resistance in Cancer: An Overview". Cancers. 6 (3): 1769–1792. doi:10.3390/cancers6031769. PMC 4190567. PMID 25198391. 13. ^ Kantharidis, Phillip; El-Oska, Assam; de Silva, Michelle; et al. (November 1997). "Altered methylation of the human MDR1 promoter is associated with acquired multidrug resistance". Clinical Cancer Research. 3 (11): 2025–2032. PMID 9815593. 14. ^ Worm, J.; Kirkin, A. F.; Dzhandzhugazyan, K. N.; Guldberg, P. (2001-10-26). "Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells". The Journal of Biological Chemistry. 276 (43): 39990–40000. doi:10.1074/jbc.M103181200. ISSN 0021-9258. PMID 11509559. 15. ^ Christmann, Markus; Pick, Matthias; Lage, Hermann; et al. (2001-04-01). "Acquired resistance of melanoma cells to the antineoplastic agent fotemustine is caused by reactivation of the DNA repair gene mgmt". International Journal of Cancer. 92 (1): 123–129. doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1160>3.3.co;2-m. ISSN 1097-0215. PMID 11279615. 16. ^ Al-Jamal, Hamid A. N.; Jusoh, Siti Asmaa Mat; Yong, Ang Cheng; et al. (2014-01-01). "Silencing of suppressor of cytokine signaling-3 due to methylation results in phosphorylation of STAT3 in imatinib resistant BCR-ABL positive chronic myeloid leukemia cells". Asian Pacific Journal of Cancer Prevention. 15 (11): 4555–4561. doi:10.7314/apjcp.2014.15.11.4555. ISSN 1513-7368. PMID 24969884. 17. ^ Mickley, L A; Spengler, B A; Knutsen, T A; Biedler, J L; Fojo, T (1997-04-15). "Gene rearrangement: a novel mechanism for MDR-1 gene activation". Journal of Clinical Investigation. 99 (8): 1947–1957. doi:10.1172/jci119362. PMC 508019. PMID 9109439. 18. ^ Hoffmeyer, S.; Burk, O.; von Richter, O.; Arnold; et al. (2000-03-28). "Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo". Proceedings of the National Academy of Sciences. 97 (7): 3473–3478. Bibcode:2000PNAS...97.3473H. doi:10.1073/pnas.97.7.3473. ISSN 0027-8424. PMC 16264. PMID 10716719. 19. ^ a b Bentires-Alj, Mohamed; Barbu, Veronique; Fillet, Marianne; Chariot, Alain; Relic, Biserka; Jacobs, Nathalie; Gielen, Jacques; Merville, Marie-Paule; Bours, Vincent (2003-01-01). "NF-κB transcription factor induces drug resistance through MDR1 expression in cancer cells". Oncogene. 22 (1): 90–97. doi:10.1038/sj.onc.1206056. ISSN 0950-9232. PMID 12527911. 20. ^ Kim, Hyung Gyun; Hien, Tran Thi; Han, Eun Hee; Hwang; et al. (2011-03-01). "Metformin inhibits P-glycoprotein expression via the NF-κB pathway and CRE transcriptional activity through AMPK activation". British Journal of Pharmacology. 162 (5): 1096–1108. doi:10.1111/j.1476-5381.2010.01101.x. ISSN 1476-5381. PMC 3051382. PMID 21054339. 21. ^ Thévenod, Frank; Friedmann, Jenny M.; Katsen, Alice D.; Hauser, Ingeborg A. (2000-01-21). "Up-regulation of Multidrug Resistance P-glycoprotein via Nuclear Factor-κB Activation Protects Kidney Proximal Tubule Cells from Cadmium- and Reactive Oxygen Species-induced Apoptosis". Journal of Biological Chemistry. 275 (3): 1887–1896. doi:10.1074/jbc.275.3.1887. ISSN 0021-9258. PMID 10636889. 22. ^ Kuo, Macus Tien; Liu, Zesheng; Wei, Yingjie; et al. (2002-03-27). "Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB signaling". Oncogene. 21 (13): 1945–1954. doi:10.1038/sj.onc.1205117. ISSN 0950-9232. PMID 11960367. 23. ^ Zhou, Ge; Kuo, M. Tien (1997-06-13). "NF-κB-mediated Induction of mdr1b Expression by Insulin in Rat Hepatoma Cells". Journal of Biological Chemistry. 272 (24): 15174–15183. doi:10.1074/jbc.272.24.15174. ISSN 0021-9258. PMID 9182539. 24. ^ Gerson, Stanton L. (2004). "MGMT: its role in cancer aetiology and cancer therapeutics". Nature Reviews Cancer. 4 (4): 296–307. doi:10.1038/nrc1319. PMID 15057289. 25. ^ Burger, H.; Nooter, K.; Boersma, A. W.; van Wingerden, K. E.; Looijenga, L. H.; Jochemsen, A. G.; Stoter, G. (1999-05-17). "Distinct p53-independent apoptotic cell death signalling pathways in testicular germ cell tumour cell lines". International Journal of Cancer. 81 (4): 620–628. doi:10.1002/(sici)1097-0215(19990517)81:4<620::aid-ijc19>3.0.co;2-s. ISSN 0020-7136. PMID 10225454. 26. ^ Youn, Cha-Kyung; Kim, Mi-Hwa; Cho, Hyun-Ju; et al. (2004-07-15). "Oncogenic H-Ras Up-Regulates Expression of ERCC1 to Protect Cells from Platinum-Based Anticancer Agents". Cancer Research. 64 (14): 4849–4857. doi:10.1158/0008-5472.CAN-04-0348. ISSN 0008-5472. PMID 15256455. 27. ^ Messina, Samantha; Leonetti, Carlo; De Gregorio, Giorgia; et al. (2004-07-23). "Ras inhibition amplifies cisplatin sensitivity of human glioblastoma". Biochemical and Biophysical Research Communications. 320 (2): 493–500. doi:10.1016/j.bbrc.2004.06.003. PMID 15219856. 28. ^ Miyashita, T; Reed, JC (January 1, 1993). "Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line". Blood. 81 (1): 151–7. doi:10.1182/blood.V81.1.151.151. PMID 8417786. 29. ^ a b Clarke, Robert; Liu, Minetta C.; Bouker, Kerrie B.; et al. (2003-01-01). "Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling". Oncogene. 22 (47): 7316–7339. doi:10.1038/sj.onc.1206937. ISSN 0950-9232. PMID 14576841. 30. ^ Nardi, Valentina; Azam, Mohammad; Daley, George Q. (2004-01-01). "Mechanisms and implications of imatinib resistance mutations in BCR-ABL". Current Opinion in Hematology. 11 (1): 35–43. doi:10.1097/00062752-200401000-00006. ISSN 1065-6251. PMID 14676625. 31. ^ a b Ganapathi, Ram; Ganapathi, Mahrukh K. (2013-01-01). "Mechanisms regulating resistance to inhibitors of topoisomerase II". Frontiers in Pharmacology. 4: 89. doi:10.3389/fphar.2013.00089. PMC 3729981. PMID 23914174. 32. ^ Schröder, Carolina P.; Godwin, Andrew K.; O'dwyer, Peter J.; et al. (1996-01-01). "Glutathione and Drug Resistance". Cancer Investigation. 14 (2): 158–168. doi:10.3109/07357909609018891. ISSN 0735-7907. PMID 8597901. 33. ^ Conze, D.; Weiss, L.; Regen, P. S.; et al. (2001-12-15). "Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells". Cancer Research. 61 (24): 8851–8858. ISSN 0008-5472. PMID 11751408. 34. ^ a b c Lee, Soo-Youn; McLeod, Howard L (2011-01-01). "Pharmacogenetic tests in cancer chemotherapy: what physicians should know for clinical application". The Journal of Pathology. 223 (1): 15–27. doi:10.1002/path.2766. ISSN 1096-9896. PMID 20818641. 35. ^ Chaudhuri AR…Nussenzweig A. Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells. Nature. July 21, 2016. DOI: 10.1038/nature18325. 36. ^ Hoffmann, Katrin; Bekeredjian, Raffi; Schmidt, Jan; et al. (2008). "Effects of the High-Affinity Peptide Reversin 121 on Multidrug Resistance Proteins in Experimental Pancreatic Cancer". Tumor Biology. 29 (6): 351–358. doi:10.1159/000178142. PMID 19039261. 37. ^ Li, Yiwei; Ahmed, Fakhara; Ali, Shadan; et al. (2005-08-01). "Inactivation of Nuclear Factor κB by Soy Isoflavone Genistein Contributes to Increased Apoptosis Induced by Chemotherapeutic Agents in Human Cancer Cells". Cancer Research. 65 (15): 6934–6942. doi:10.1158/0008-5472.CAN-04-4604. ISSN 0008-5472. PMID 16061678. 38. ^ Liu, Xiangrui; Wilcken, Rainer; Joerger, Andreas C.; et al. (2013-07-01). "Small molecule induced reactivation of mutant p53 in cancer cells". Nucleic Acids Research. 41 (12): 6034–6044. doi:10.1093/nar/gkt305. ISSN 0305-1048. PMC 3695503. PMID 23630318. 39. ^ Xu, W.; Cai, B.; Chen, J.l.; et al. (2008-07-01). "ATP7B antisense oligodeoxynucleotides increase the cisplatin sensitivity of human ovarian cancer cell line SKOV3ipl". International Journal of Gynecological Cancer. 18 (4): 718–722. doi:10.1111/j.1525-1438.2007.01085.x. ISSN 1525-1438. PMID 17944925. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Antineoplastic resistance

None

wikipedia

https://en.wikipedia.org/wiki/Antineoplastic_resistance

{"mesh": ["D019008"], "wikidata": ["Q13416904"]}

A rare, non-syndromic, hereditary palmoplantar keratoderma characterized by diffuse, yellowish, thick hyperkeratosis of the palms and soles with a sharp demarcation at the volar border and an erythematous margin, and the epidermolytic pattern of changes on the skin biopsy, including perinuclear vacuolization, granular degeneration of keratinocytes in the spinous and granular layer, and tonofilament aggregates. Painful fissures and hyperhidrosis are frequently associated. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Epidermolytic palmoplantar keratoderma

c1721006

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2199

{"gard": ["2826"], "mesh": ["D053546"], "omim": ["144200"], "umls": ["C0343110", "C1721006", "C2931735"], "icd-10": ["Q82.8"], "synonyms": ["Diffuse erythrodermic palmoplantar keratoderma, Voerner type", "Diffuse erythrodermic palmoplantar keratoderma, Vörner type", "EPPK", "Epidermolytic palmoplantar keratoderma of Voerner", "Epidermolytic palmoplantar keratoderma of Vörner"]}

Hyperpathia is a clinical symptom of certain neurological disorders wherein nociceptive stimuli evoke exaggerated levels of pain. This should not be confused with allodynia, where normally non-painful stimuli evoke pain. ## Mechanism[edit] Hyperpathia describes the neuropathic pain which the pain threshold on one hand is elevated and the other hand is central hyperexcited whenever there is a loss of fibres. Hyperpathia is underlying the peripheral or central deafferentation when the afferent inputs are lost.[1] Hyperpathia only occurs on neuropathic pain patients with the loss of fibres. The International Association of the Study of Pain's (IASP) definition of hyperpathia is that: A painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold. The definition also complies with a note which is: It may occur with allodynia, hyperesthesia, hyperalgesia, or dysesthesia. Faulty identification and localization of the stimulus, delay, radiating sensation, and after-sensation may be present, and the pain is often explosive in character. The changes in this note are the specification of allodynia and the inclusion of hyperalgesia explicitly. Previously hyperalgesia was implied, since hyperesthesia was mentioned in the previous note and hyperalgesia is a special case of hyperesthesia.[2] ## References[edit] 1. ^ Jensen, T. S. (1996). Mechanisms of neuropathic pain. In J. N. Campbell (Ed.), Pain, 1996, an updated review. (pp. 77-86). Seattle: IASP Press 2. ^ (I.A.S.P, 1986). Pain Supplement 3: Classification of Chronic Pain, Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Amsterdam: Elsevier. * v * t * e Pain By region/system Head and neck * Headache * Neck * Odynophagia (swallowing) * Toothache Respiratory system * Sore throat * Pleurodynia Musculoskeletal * Arthralgia (joint) * Bone pain * Myalgia (muscle) * Acute * Delayed-onset Neurologic * Neuralgia * Pain asymbolia * Pain disorder * Paroxysmal extreme pain disorder * Allodynia * Chronic pain * Hyperalgesia * Hypoalgesia * Hyperpathia * Phantom pain * Referred pain * Congenital insensitivity to pain * congenital insensitivity to pain with anhidrosis * congenital insensitivity to pain with partial anhidrosis Other * Pelvic pain * Proctalgia * Back * Low back pain Measurement and testing * Pain scale * Cold pressor test * Dolorimeter * Grimace scale (animals) * Hot plate test * Tail flick test * Visual analogue scale Pathophysiology * Nociception * Anterolateral system * Posteromarginal nucleus * Substance P Management * Analgesia * Anesthesia * Cordotomy * Pain eradication Related concepts * Pain threshold * Pain tolerance * Suffering * SOCRATES * Philosophy of pain * Cancer pain * Drug-seeking behavior This medical symptom article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Hyperpathia

c0020429

wikipedia

https://en.wikipedia.org/wiki/Hyperpathia

{"mesh": ["D006930"], "wikidata": ["Q536517"]}

Transient neonatal myasthenia gravis (MG) is a rare form of MG (see this term) occurring in neonates born to mothers who have the disorder or specific circulating autoantibodies. ## Epidemiology Exact incidence data are not available. The disorder occurs in 10% to 20% of children born to mothers with myasthenia gravis. ## Clinical description In some cases, the mother may be asymptomatic. Severity is generally not correlated with maternal disease but possibly with maternal antibody titers. Onset is usually within the first hours of life. Transient neonatal MG manifests as hypotonia, feeding difficulties, weak cry, facial diplegia and respiratory difficulties in affected neonates. With the gradual decrease in maternally-derived antibodies, the symptoms usually resolve. Subsequent births to the same mother are also at risk of this disorder. Risk factors for the condition are currently not clear. Rapid treatment usually enables resolution of the condition by 2 months of age. ## Etiology The disorder is related to passive transplacental transfer of maternal anti-acetylcholine receptorantibodies (anti-AChR) or anti-muscle-specific tyrosine kinase antibodies (anti-MuSK) to the neonate. Circulating autoimmune antibodies are thought to damage the post-synaptic neuromuscular junction. The fetal onset form is related to antibodies directed against fetal AChR. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Transient neonatal myasthenia gravis

c0495465

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=391504

{"mesh": ["D020941"], "umls": ["C0158982", "C0495465"], "icd-10": ["P94.0"], "synonyms": ["NMG", "Neonatal myasthenia gravis", "Transient neonatal acquired myasthenia", "Transient neonatal autoimmune myasthenia gravis"]}

For a general phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see (600669). Clinical Features Kinirons et al. (2008) identified 20 French Canadian families with autosomal dominant generalized epilepsy. Mapping By linkage analysis in a large French Canadian family segregating idiopathic generalized epilepsy, Kinirons et al. (2008) identified a candidate locus on chromosome 10p11.22 (2-point lod score of 3.05 and multipoint lod score of 3.18 at D10S1426). Haplotype analysis delineated a 6.5-Mb region. Three other large potentially informative families did not link to this region or to any other and were excluded from further studies. Multipoint linkage analysis using 16 additional families yielded a maximum lod score under heterogeneity of 4.23 (alpha = 0.34) at this locus. Evaluation of recombination breakpoints in these families narrowed the candidate region to 1.7 Mb. Molecular analysis excluded mutations in the coding regions of the NRP1 (602069) and PARD3 (606745) genes. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 5

c2677808

omim

https://www.omim.org/entry/611934

{"omim": ["611934"], "synonyms": ["Alternative titles", "EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, LOCUS ON CHROMOSOME 10"]}

A type of HCD characterized by the production of incomplete monoclonal alpha-heavy chains without associated light chains. Alpha-HCD is considered to be a subtype of immunoproliferative small intestinal disease (IPSID). The clinical presentation includes chronic diarrhea with evidence of malabsorption. ## Epidemiology The prevalence of the disease is unknown but most cases have been from North African and Middle Eastern/Mediterranean countries and have been associated with poor sanitation. There have been more than 400 cases reported in the world literature. ## Clinical description Alpha-HCD has a predilection for young age groups (20-30 years). Patients present with symptoms of malabsorption. Diarrhea, weight loss and abdominal pain are common. Parasitic infections are often present. Infiltration of the jejunal mucosa with plasmacytoid cells is the most frequent pathologic feature. Immunoblastic lymphoma occurs as the disease progresses. ## Etiology The exact cause of alpha-HCD is unknown. The lymphoplasmacytic infiltration of the intestinal mucosa is felt to be a response of the alimentary tract immune system to prolonged luminal antigenic stimulation by intestinal organisms. ## Diagnostic methods The diagnosis of alpha-HCD is based on identification of free alpha-heavy chains without associated light chains. Truncated alpha-heavy chains can be detected in biological fluids (serum, urine, jejunal secretions) by immunoelectrophoresis, immunoselection, or immunofixation. ## Differential diagnosis Alpha-HCD disease must be differentiated from non-Hodgkin lymphoma (NHL; see this term), although this is an uncommon diagnosis in the age range typical of alpha-HCD. Other causes of small bowel malabsorption need to be considered, especially celiac disease (see this term). ## Management and treatment Initial treatment consists of eradication of any concurrent infection (e.g., parasites, viruses, Helicobacter pylori, Campylobacter jejuni) with appropriate antibiotics. For patients with symptomatic disease not responding adequately to antibiotics, chemotherapy similar to that used to treat NHL is recommended. Surgical resection is sometimes needed when bulky masses are present. ## Prognosis The disease course of alpha-HCD is variable and long-term prognosis of the disease is imprecise. Without antibiotics and chemotherapy the disease progresses rapidly and prognosis is poor. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Alpha-heavy chain disease

c0021071

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100025

{"mesh": ["D007161"], "umls": ["C0021071"], "icd-10": ["C88.3"], "synonyms": ["Alpha-HCD", "IPSID", "Immunoproliferative small intestinal disease", "Mediterranean lymphoma"]}

"NTOS" redirects here. For the Windows NT microkernel used in computing, see Windows NT kernel. Thoracic outlet syndrome The right brachial plexus, viewed from in front. SpecialtyVascular surgery, thoracic surgery SymptomsPain, weakness, loss of muscle at the base of the thumb, swelling, paleness, bluish coloration[1][2] Usual onset20 to 50 years of age[1] TypesNeurogenic, venous, arterial[1] CausesCompression of the nerves, arteries, or veins in the passageway from the lower neck to the armpit[1] Risk factorsTrauma, repetitive arm movements, tumors, pregnancy, cervical rib[1] Diagnostic methodNerve conduction studies, medical imaging[1] Differential diagnosisRotator cuff tear, cervical disc disorders, fibromyalgia, multiple sclerosis, complex regional pain syndrome[1] TreatmentPain medication, surgery[1][2] Frequency~1%[3] Thoracic outlet syndrome (TOS) is a condition in which there is compression of the nerves, arteries, or veins in the passageway from the lower neck to the armpit.[1] There are three main types: neurogenic, venous, and arterial.[1] The neurogenic type is the most common and presents with pain, weakness, and occasionally loss of muscle at the base of the thumb.[1][2] The venous type results in swelling, pain, and possibly a bluish coloration of the arm.[2] The arterial type results in pain, coldness, and paleness of the arm.[2] TOS may result from trauma, repetitive arm movements, tumors, pregnancy, or anatomical variations such as a cervical rib.[1] The diagnosis may be supported by nerve conduction studies and medical imaging.[1] Other conditions that can produce similar symptoms include rotator cuff tear, cervical disc disorders, fibromyalgia, multiple sclerosis, and complex regional pain syndrome.[1] Initial treatment for the neurogenic type is with exercises to strengthen the chest muscles and improve posture.[1] NSAIDs such as naproxen may be used for pain.[1] Surgery is typically done for the arterial and venous types and for the neurogenic type if it does not improve with other treatments.[1][2] Blood thinners may be used to treat or prevent blood clots.[1] The condition affects about 1% of the population.[3] It is more common in women than men and it occurs most commonly between 20 and 50 years of age.[1] The condition was first described in 1818 and the current term "thoracic outlet syndrome" first used in 1956.[2][4] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 Classification * 3.1.1 By structures affected and symptomatology * 3.1.2 By event * 3.1.3 By structure causing constriction * 4 Treatment * 4.1 Physical measures * 4.2 Medications * 4.3 Surgery * 5 Notable cases * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] TOS affects mainly the upper limbs, with signs and symptoms manifesting in the shoulders, neck, arms and hands. Pain can be present on an intermittent or permanent basis. It can be sharp/stabbing, burning, or aching. TOS can involve only part of the hand (as in the pinky and adjacent half of the ring finger), all of the hand, or the inner aspect of the forearm and upper arm. Pain can also be in the side of the neck, the pectoral area below the clavicle, the armpit/axillary area, and the upper back (i.e., the trapezius and rhomboid area). Discoloration of the hands, one hand colder than the other hand, weakness of the hand and arm muscles, and tingling are commonly present.[citation needed] Only 1% of people with carpal tunnel syndrome have concomittent TOS.[5] Repetitive motions can cause enlargement of muscles which causes compression of veins. Besides, overuse injury of the upper limbs causes swellings, small bleeding, and subsequent fibrosis which would cause the thrombosis of the subclavian vein, leading to Paget–Schroetter disease or effort-induced thrombosis.[5] TOS can be related to cerebrovascular arterial insufficiency when affecting the subclavian artery.[6] It also can affect the vertebral artery, in which case it could produce vision disturbances, including transient blindness,[7] and embolic cerebral infarction.[8] TOS can also lead to eye problems and vision loss as a circumstance of vertebral artery compression. Although very rare, if compression of the brain stem is also involved in an individual presentation of TOS, transient blindness may occur while the head is held in certain positions.[7] If left untreated, TOS can lead to neurological deficits as a result of the hypoperfusion and hypometabolism of certain areas of the brain and cerebellum.[9] ## Causes[edit] Thoracic outlet syndrome TOS can be attributed to one or more of the following factors:[10] * Congenital abnormalities are frequently found in persons with TOS. These include cervical rib, prolonged transverse process, and muscular abnormalities (e.g., in the scalenus anterior muscle, a sickle-shaped scalenus medius) or fibrous connective tissue anomalies.[10] * Trauma (e.g., whiplash injuries) or repetitive strain is frequently implicated.[10] * Rarer acquired causes include tumors (especially pancoast tumor), hyperostosis, and osteomyelitis[10] ## Diagnosis[edit] Adson's sign and the costoclavicular maneuver lack specificity and sensitivity and should comprise only a small part of the mandatory comprehensive history and physical examination undertaken with a patient suspected of having TOS. There is currently no single clinical sign that makes the diagnosis of TOS with any degree of certainty.[citation needed] Additional maneuvers that may be abnormal in TOS include Wright's Test, which involves hyperabducting the arms over the head with some extension and evaluating for loss of radial pulses or signs of blanching of the skin in the hands indicating a decrease in blood flow with the maneuver. The "compression test" is also used, exerting pressure between the clavicle and medial humeral head causes radiation of pain and/or numbness into the affected arm.[11] Doppler arteriography, with probes at the fingertips and arms, tests the force and "smoothness" of the blood flow through the radial arteries, with and without having the patient perform various arm maneuvers (which causes compression of the subclavian artery at the thoracic outlet). The movements can elicit symptoms of pain and numbness and produce graphs with diminished arterial blood flow to the fingertips, providing strong evidence of impingement of the subclavian artery at the thoracic outlet.[12] Doppler arteriography does not utilize probes at the fingertips and arms, and in this case is likely being confused with plethysmography, which is a different method that utilizes ultrasound without direct visualization of the affected vessels. Doppler ultrasound (not really 'arteriography') would not be used at the radial artery in order to make the diagnosis of TOS. Finally, even if a Doppler study of the appropriate artery were to be positive, it would not diagnose neurogenic TOS, by far the most common subtype of TOS. There is plenty of evidence in the medical literature to show that arterial compression does not equate to brachial plexus compression, although they may occur together, in varying degrees. Additionally, arterial compression by itself does not make the diagnosis of arterial TOS (the rarest form of TOS). Lesser degrees of arterial compression have been shown in normal individuals in various arm positions and are thought to be of little significance without the other criteria for arterial TOS. MRI scan can show the anatomy of the thoracic outlet, the soft tissues causing compression, and can show directly the brachial plexus compression.[5] ### Classification[edit] #### By structures affected and symptomatology[edit] There are three main types of TOS, named according to the cause of the symptoms; however, these three classifications have been coming into disfavor because TOS can involve all three types of compression to various degrees. The compression can occur in three anatomical structures (arteries, veins and nerves), it can be isolated, or, more commonly, two or three of the structures are compressed to greater or lesser degrees. In addition, the compressive forces can be of different magnitude in each affected structure. Therefore, symptoms can be variable.[13] * Neurogenic TOS includes disorders produced by compression of components of the brachial plexus nerves. The neurogenic form of TOS accounts for 95% of all cases of TOS.[14] * Arterial TOS is due to compression of the subclavian artery.[14] This is less than one percent of cases.[2] * Venous TOS is due to compression of the subclavian vein.[14] This makes up about 4% of cases.[2] #### By event[edit] There are many causes of TOS. The most frequent cause is trauma, either sudden (as in a clavicle fracture caused by a car accident), or repetitive (as in a legal secretary who works with his/her hands, wrists, and arms at a fast paced desk station with non-ergonomic posture for many years)[citation needed]. TOS is also found in certain occupations involving much lifting of the arms and repetitive use of the wrists and arms[citation needed]. One cause of arterial compression is trauma, and a recent case involving fracture of the clavicle has been reported.[15] The two groups of people most likely to develop TOS are those suffering from neck injuries due to traffic accidents and those who use computers in non-ergonomic postures for extended periods of time.[citation needed] TOS is frequently a repetitive stress injury (RSI) caused by certain types of work environments[citation needed]. #### By structure causing constriction[edit] It is also possible to classify TOS by the location of the obstruction:[citation needed] * Anterior scalene syndrome (compression on brachial plexus and/or subclavian artery caused by muscle growth). * Cervical rib syndrome (compression on brachial plexus and/or subclavian artery caused by bone growth). * Costoclavicular syndrome (narrowing between the clavicle and the first rib) – diagnosed with the costoclavicular maneuver. Some people are born with an extra incomplete and very small rib above their first rib, which protrudes out into the superior thoracic outlet space. This rudimentary rib causes fibrous changes around the brachial plexus nerves, inducing compression and causing the symptoms and signs of TOS. This is called a "cervical rib" because of its attachment to C-7 (the seventh cervical vertebra), and its surgical removal is almost always recommended. The symptoms of TOS can first appear in the early teen years as a child is becoming more athletic. ## Treatment[edit] Evidence for the treatment of thoracic outlet syndrome as of 2014 is poor.[16] ### Physical measures[edit] Stretching, occupational and physical therapy are common non-invasive approaches used in the treatment of TOS. The goal of stretching is to relieve compression in the thoracic cavity, reduce blood vessel and nerve impingement, and realign the bones, muscles, ligaments, or tendons that are causing the problem.[citation needed] * One commonly prescribed set of stretches includes moving the shoulders anteriorly (forward – called "hunching"), then back to a neutral position, then extending them posteriorly (backward, called "arching"), then back to neutral, followed by lifting the shoulders up as high as possible, and then back down to neutral, repeated in cycles as tolerated. * Another set of stretches involves tilting and extending the neck opposite to the side of the injury while keeping the injured arm down or wrapped around the back. * Occupational or Physical therapy can include passive or active range of motion exercises, working up to weighted or restricted sets (as tolerated). TOS is rapidly aggravated by poor posture.[citation needed] Active breathing exercises and ergonomic desk setup and motion practices can help maintain active posture.[citation needed] Often the muscles in the back become weak due to prolonged (years of) "hunching" and other poor postures.[citation needed] Ice can be used to decrease inflammation of sore or injured muscles. Heat can also aid in relieving sore muscles by improving blood circulation to them. While the whole arm generally feels painful in TOS, some relief can be seen when ice or heat is intermittently applied to the thoracic region (collar bone, armpit, or shoulder blades).[citation needed] ### Medications[edit] In a review, botox was compared to a placebo injected into the scalene muscles. No effect in terms of pain relief or improved movement was noted. However in a six-months follow-up, paresthesia (abnormal sensations such as in pins and needles) was seen to be significantly improved.[16] ### Surgery[edit] Surgical approaches have also been used successfully in TOS. Microsurgery can be used approaching the area from above the collar bone (supraclavicular) followed by neurolysis of the brachial plexus, removal of the scalene muscle (scalenectomy), and the release of the underlying (subclavicular) blood vessels. This approach avoids the use of resection, and has been found to be an effective treatment.[17] In cases where the first rib (or a fibrous band extending from the first rib) is compressing a vein, artery, or the nerve bundle, part of the first rib and any compressive fibrous tissue, can be removed in a first rib resection and thoracic outlet decompression surgical procedure; scalene muscles may also need to be removed (scalenectomy). This allows increased blood flow and the reduction of nerve compression.[18] In some cases there may be a rudimentary rib or a cervical rib that can be causing the compression, which can be removed using the same technique.[citation needed] Physical therapy is often used before and after the operation to improve recovery time and outcomes. Potential complications include pneumothorax, infection, loss of sensation, motor problems, subclavian vessel damage, and, as in all surgeries, a very small risk of permanent serious injury or death.[citation needed] ## Notable cases[edit] Sports Several Major League Baseball players, especially pitchers, have been diagnosed with thoracic outlet syndrome, including Chris Archer, Matt Harvey,[19] Chris Carpenter,[20] Jaime Garcia,[21] Shaun Marcum,[22] Matt Harrison,[23] Clayton Richard,[24] Nate Karns,[25] and Noah Lowry.[26] Starting pitcher Chris Young, who previously struggled with shoulder problems, underwent surgery for TOS in 2013 and felt "completely different" post-recovery.[27] Young exceeded expectations on his return to the major leagues at age 35, becoming a valuable member of the 2014 Seattle Mariners' starting rotation.[28] NHL defenseman Adam McQuaid was diagnosed with TOS in September 2012, and as a result was nominated for the Bill Masterton Memorial Trophy.[29] Forward Chris Kreider was diagnosed with a malformed rib in 2017. Kreider dealt with multiple symptoms prior to the diagnosis, such as shortness of breath on the ice, swelling/numbness in his right arm, coughing up blood and a blod clot in his right arm. Kreider underwent successful surgery to resect a rib in January 2018 (the same surgery as TOS) and has performed well since returning to the Rangers.[30] NBA guard Markelle Fultz was diagnosed with TOS in December 2018.[31][32] UFC fighter Matt Serra had a rib removed to alleviate TOS.[33] Music Musician Isaac Hanson had a pulmonary embolism as a consequence of thoracic outlet syndrome.[34] The Japanese band Maria disbanded in 2010 due to drummer Tattsu's TOS which made it impossible for her to continue playing.[35] In 2015, singer Tamar Braxton had to leave Dancing With The Stars due to TOS.[36] ## See also[edit] * May–Thurner syndrome – a similar compressive pathology involving the left common iliac vein * Backpack palsy – a similar compressive pathology involving the long thoracic nerve, or adjacent brachial plexis nerves ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s "NINDS Thoracic Outlet Syndrome Information Page". NINDS. December 28, 2011. Archived from the original on July 27, 2016. Retrieved August 19, 2016. 2. ^ a b c d e f g h i Kuhn JE, Lebus V GF, Bible JE (April 2015). "Thoracic outlet syndrome". The Journal of the American Academy of Orthopaedic Surgeons. 23 (4): 222–32. doi:10.5435/jaaos-d-13-00215. PMID 25808686. S2CID 23150937. 3. ^ a b Moore WS (2012). Vascular and Endovascular Surgery: A Comprehensive Review (8 ed.). Elsevier Health Sciences. p. 524. ISBN 978-1-4557-5386-4. 4. ^ Lee JT, Jordan SE, Illig KA (2014). "Clinical incidence and prevalence: basic data on the current scope of the problem.". In Illig KA, Thompson RW, Freischlag JA, Donahue DM, Jordan SE, Edgelow PI (eds.). Thoracic Outlet Syndrome. London: Springer Science & Business Media. pp. 25–28. ISBN 978-1-4471-4366-6. 5. ^ a b c Jones MR, Prabhakar A, Viswanath O, Urits I, Green JB, Kendrick JB, et al. (June 2019). "Thoracic Outlet Syndrome: A Comprehensive Review of Pathophysiology, Diagnosis, and Treatment". Pain and Therapy. 8 (1): 5–18. doi:10.1007/s40122-019-0124-2. PMC 6514035. PMID 31037504. 6. ^ Thetter O, van Dongen RJ, Barwegen MG (1985). "[The thoracic outlet compression syndrome and its vascular complications]". Zentralblatt für Chirurgie. 110 (8): 449–56. PMID 4002908. 7. ^ a b Sell JJ, Rael JR, Orrison WW (October 1994). "Rotational vertebrobasilar insufficiency as a component of thoracic outlet syndrome resulting in transient blindness. Case report". Journal of Neurosurgery. 81 (4): 617–9. doi:10.3171/jns.1994.81.4.0617. PMID 7931599. 8. ^ Nishibe T, Kunihara T, Kudo FA, Adachi A, Shiiya N, Murashita T, et al. (December 2000). "Arterial thoracic outlet syndrome with embolic cerebral infarction. Report of a case". Panminerva Medica. 42 (4): 295–7. PMID 11294095. 9. ^ Fernandez Noda EI, Nuñez-Arguelles J, Perez Fernandez J, Castillo J, Perez Izquierdo M, Rivera Luna H (December 1996). "Neck and brain transitory vascular compression causing neurological complications. Results of surgical treatment on 1,300 patients". The Journal of Cardiovascular Surgery. 37 (6 Suppl 1): 155–66. PMID 10064369. 10. ^ a b c d Laulan J, Fouquet B, Rodaix C, Jauffret P, Roquelaure Y, Descatha A (September 2011). "Thoracic outlet syndrome: definition, aetiological factors, diagnosis, management and occupational impact". Journal of Occupational Rehabilitation. 21 (3): 366–73. doi:10.1007/s10926-010-9278-9. PMC 3526474. PMID 21193950. 11. ^ "Thoracic Outlet Syndrome". Nicholas Institute of Sports Medicine and Athletic Trauma. Archived from the original on May 17, 2013. 12. ^ "Thoracic outlet syndrome". Mount Sinai Hospital, New York. Archived from the original on December 9, 2008. 13. ^ Ambrad-Chalela E, Thomas GI, Johansen KH (April 2004). "Recurrent neurogenic thoracic outlet syndrome". American Journal of Surgery. 187 (4): 505–10. doi:10.1016/j.amjsurg.2003.12.050. PMID 15041500. 14. ^ a b c Fugate MW, Rotellini-Coltvet L, Freischlag JA (April 2009). "Current management of thoracic outlet syndrome". Current Treatment Options in Cardiovascular Medicine. 11 (2): 176–83. doi:10.1007/s11936-009-0018-4. PMID 19289030. S2CID 23667734. 15. ^ Burnand KM, Lagocki S, Lahiri RP, Tang TY, Patel AD, Clarke JM (2010). "Persistent subclavian artery stenosis following surgical repair of non-union of a fractured clavicle". Grand Rounds. 10: 55–8. doi:10.1102/1470-5206.2010.0012 (inactive December 26, 2020). Archived (PDF) from the original on July 11, 2011.CS1 maint: DOI inactive as of December 2020 (link) 16. ^ a b Povlsen B, Hansson T, Povlsen SD (November 2014). "Treatment for thoracic outlet syndrome". The Cochrane Database of Systematic Reviews. 11 (11): CD007218. doi:10.1002/14651858.CD007218.pub3. PMID 25427003. 17. ^ Rochkind S, Shemesh M, Patish H, Graif M, Segev Y, Salame K, et al. (2007). "Thoracic outlet syndrome: a multidisciplinary problem with a perspective for microsurgical management without rib resection". Acta Neurochirurgica. Supplement. Acta Neurochirurgica Supplementum. 100: 145–7. doi:10.1007/978-3-211-72958-8_31. ISBN 978-3-211-72955-7. PMID 17985565. 18. ^ Köknel Talu G (April 2005). "Thoracic outlet syndrome". Agri. 17 (2): 5–9. PMID 15977087. 19. ^ DiComo A (February 13, 2017). "Harvey determined to regain dominant form". MLB News. 20. ^ Langosch J, Still M (July 2, 2012). "Carpenter's throwing session canceled". MLB.com. Archived from the original on October 29, 2013. 21. ^ Halsted A (July 5, 2014). "Garcia to have season-ending surgery for nerve issue". MLB.com. Archived from the original on July 14, 2014. 22. ^ "Marcum needs thoracic outlet syndrome surgery". Rotoworld.com. July 9, 2013. Archived from the original on July 12, 2013. 23. ^ Fort Worth Star-Telegram (September 7, 2013). "Foul Territory: Rangers' Matt Harrison facing surgery for thoracic outlet syndrome on right shoulder". Sportsblogs.star-telegram.com. Archived from the original on October 29, 2013. Retrieved October 26, 2013. 24. ^ "Clayton Richard's Story". Center for Thoracic Outlet Syndrome. Washington University School of Medicine in St Louis. Archived from the original on April 16, 2016. Retrieved April 9, 2016. 25. ^ Jul 15, A. P.; ET, 2017 at 6:21p (July 15, 2017). "Nate Karns out for season due to thoracic outlet surgery". FOX Sports. Retrieved October 12, 2020. 26. ^ Shea J, Schulman H (May 20, 2009). "San Francisco Chronicle: Lowry's agent lashes out". Sfgate.com. Archived from the original on May 23, 2009. Retrieved October 26, 2013. 27. ^ Wagner J (March 12, 2014). "Nationals Journal: Back from injury, Chris Young hopes to be part of the Nationals". The Washington Post. Retrieved October 19, 2014. 28. ^ Stecker B (August 18, 2014). "Mariners' Chris Young has strong case for Comeback award". 710Sports.com. Archived from the original on August 22, 2014. Retrieved October 19, 2014. 29. ^ Marrapese-Burrell N. "McQuaid a Masterton Trophy Finalist". Boston Globe. Archived from the original on June 8, 2013. Retrieved June 8, 2013. 30. ^ Kaplan E (August 2, 2018). "Inside Chris Kreider's journey back to the ice". ESPN. 31. ^ "Markelle Fultz diagnosed with nerve condition". NBA.com. 32. ^ Wojnarowski A. "76ers' Markelle Fultz expected to miss 3-6 weeks for shoulder rehabilitation". ESPN. Retrieved December 4, 2018. 33. ^ Burke T (May 22, 2013). "Health scare leads to former UFC champion Matt Serra probably walking away from MMA". Bloody Elbow. Archived from the original on October 29, 2013. Retrieved October 26, 2013. 34. ^ Dyball R, Schneider KS (October 22, 2007). "Anson Brother's Health Scare 'I Could Have Silently Died'". People. New York. 68 (17): 96. Archived from the original on October 18, 2007. Retrieved January 1, 2008. "Isaac hanson talks about surviving a life-threatening blood clot--and how his family is helping him cope." 35. ^ "MARIA今後の活動に関するお知らせ" (in Japanese). MARIA6. Archived from the original on February 11, 2010. Retrieved February 16, 2010. 36. ^ "Tamar Braxton Opens up About Health Crisis, Rib Removal". ABC News. December 17, 2015. ## External links[edit] Classification D * ICD-10: G54.0 * ICD-9-CM: 353.0 * MeSH: D013901 * DiseasesDB: 13039 External resources * MedlinePlus: 001434 * eMedicine: pmr/136 * Patient UK: Thoracic outlet syndrome * Orphanet: 97330 * thoracic at NINDS * v * t * e Diseases relating to the peripheral nervous system Mononeuropathy Arm median nerve * Carpal tunnel syndrome * Ape hand deformity ulnar nerve * Ulnar nerve entrapment * Froment's sign * Ulnar tunnel syndrome * Ulnar claw radial nerve * Radial neuropathy * Wrist drop * Cheiralgia paresthetica long thoracic nerve * Winged scapula * Backpack palsy Leg lateral cutaneous nerve of thigh * Meralgia paraesthetica tibial nerve * Tarsal tunnel syndrome plantar nerve * Morton's neuroma superior gluteal nerve * Trendelenburg's sign sciatic nerve * Piriformis syndrome Cranial nerves * See Template:Cranial nerve disease Polyneuropathy and Polyradiculoneuropathy HMSN * Charcot–Marie–Tooth disease * Dejerine–Sottas disease * Refsum's disease * Hereditary spastic paraplegia * Hereditary neuropathy with liability to pressure palsy * Familial amyloid neuropathy Autoimmune and demyelinating disease * Guillain–Barré syndrome * Chronic inflammatory demyelinating polyneuropathy Radiculopathy and plexopathy * Brachial plexus injury * Thoracic outlet syndrome * Phantom limb Other * Alcoholic polyneuropathy Other General * Complex regional pain syndrome * Mononeuritis multiplex * Peripheral neuropathy * Neuralgia * Nerve compression syndrome *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Thoracic outlet syndrome

c0039984

wikipedia

https://en.wikipedia.org/wiki/Thoracic_outlet_syndrome

{"gard": ["7759"], "mesh": ["D013901"], "umls": ["C0039984"], "icd-9": ["353.0"], "orphanet": ["97330"], "wikidata": ["Q665207"]}

Benign chronic familial pemphigus of Hailey-Hailey is characterized by rhagades mostly located in the armpits, inguinal and perineal folds (scrotum, vulva). ## Epidemiology Prevalence is unknown. ## Clinical description Skin lesions appear during adolescence or more often at the age of 30-40 years; they are relapsing and recurrent. Lesions can be complicated by heat, rubbing or superinfections. ## Etiology Mutations in the ATP2C1 gene (localised to 3q21-q24), encoding a calcium pump, cause the disease by impairing epidermal keratinocyte adhesion. ## Diagnostic methods Histopathological analysis of the lesions shows suprabasal acantholysis of epidermal cells. ## Genetic counseling Benign chronic familial pemphigus is transmitted as a dominant trait, with incomplete penetrance. ## Management and treatment There is no specific treatment, but drying the affected areas is essential as well as employing measures to prevent bacterial, fungal and viral infections. Topical medical treatment can alleviate the symptoms in milder forms. Physical treatments are very effective for more severe forms: CO2 laser therapy (pulse or continuous) is often proposed as a first-line treatment. Other techniques, such as dermabrasion or excision-graft, may also be required to correct the symptoms of this dermatosis. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Familial benign chronic pemphigus

c0085106

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2841

{"gard": ["6559"], "mesh": ["D016506"], "omim": ["169600"], "umls": ["C0085106"], "icd-10": ["Q82.8"], "synonyms": ["Benign chronic familial pemphigus of Hailey-Hailey", "Hailey-Hailey disease"]}

Activated protein C resistance (APCR) Protein C Anticoagulant Pathway: Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. Activated protein C (APC) functions as a circulating anticoagulant, which specifically degrades and inactivates the phospholipid-bound factors Va and VIIIa. This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S SpecialtyHematology Activated protein C resistance (APCR) is a hypercoagulability (an increased tendency of the blood to clot) characterized by a lack of a response to activated protein C (APC), which normally helps prevent blood from clotting excessively. This results in an increased risk of venous thrombosis (blood clots in veins), which resulting in medical conditions such as deep vein thrombosis (usually in the leg) and pulmonary embolism (in the lung, which can cause death).[1] ## Contents * 1 Presentation * 1.1 Associated conditions * 2 Genetics * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 6 References * 7 External links ## Presentation[edit] ### Associated conditions[edit] An estimated 64 percent of patients with venous thromboembolism may have activated protein C resistance.[2][needs update] ## Genetics[edit] The disorder can be acquired or inherited, the hereditary form having an autosomal dominant inheritance pattern.[3] ## Pathophysiology[edit] Activated protein C (with protein S as a cofactor) degrades Factor Va and Factor VIIIa. Activated protein C resistance is the inability of protein C to cleave Factor Va and/or Factor VIIIa, which allows for longer duration of thrombin generation and may lead to a hypercoagulable state. This may be hereditary or acquired.[4] The best known and most common hereditary form is Factor V Leiden. Acquired forms occur in the presence of elevated Factor VIII concentrations. ## Diagnosis[edit] "APC(Activated protein C) ratio: To diagnose functional assays | PCR(Polymerase chain reaction)/ Restriction enzyme analysis: To detect the specific genetic anomaly responsible for FVL(factor V Leiden)[citation needed] " ## Treatment[edit] This section is empty. You can help by adding to it. (October 2017) ## References[edit] 1. ^ Dahlbäck B (2003). "The discovery of activated protein C resistance". J. Thromb. Haemost. 1 (1): 3–9. doi:10.1046/j.1538-7836.2003.00016.x. PMID 12871530. S2CID 2147784. 2. ^ Sheppard DR (2000). "Activated protein C resistance: the most common risk factor for venous thromboembolism". J Am Board Fam Pract. 13 (2): 111–5. doi:10.3122/15572625-13-2-111. PMID 10764192. S2CID 20016675. 3. ^ Koster T, Rosendaal FR, De Ronde H, Briët E, Vandenbroucke JP, Bertina RM (December 1993). "Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study". Lancet. 342 (8886–8887): 1503–6. doi:10.1016/S0140-6736(05)80081-9. ISSN 0140-6736. PMID 7902898. S2CID 54283312. 4. ^ Nicolaes GA, Dahlbäck B (2003). "Congenital and acquired activated protein C resistance". Semin Vasc Med. 3 (1): 33–46. doi:10.1055/s-2003-38331. PMID 15199491. ## External links[edit] Classification D * ICD-10: D68.51 * OMIM: 188055 * MeSH: D020016 * v * t * e Disorders of bleeding and clotting Coagulation · coagulopathy · Bleeding diathesis Clotting By cause * Clotting factors * Antithrombin III deficiency * Protein C deficiency * Activated protein C resistance * Protein S deficiency * Factor V Leiden * Prothrombin G20210A * Platelets * Sticky platelet syndrome * Thrombocytosis * Essential thrombocythemia * DIC * Purpura fulminans * Antiphospholipid syndrome Clots * Thrombophilia * Thrombus * Thrombosis * Virchow's triad * Trousseau sign of malignancy By site * Deep vein thrombosis * Bancroft's sign * Homans sign * Lisker's sign * Louvel's sign * Lowenberg's sign * Peabody's sign * Pratt's sign * Rose's sign * Pulmonary embolism * Renal vein thrombosis Bleeding By cause Thrombocytopenia * Thrombocytopenic purpura: ITP * Evans syndrome * TM * TTP * Upshaw–Schulman syndrome * Heparin-induced thrombocytopenia * May–Hegglin anomaly Platelet function * adhesion * Bernard–Soulier syndrome * aggregation * Glanzmann's thrombasthenia * platelet storage pool deficiency * Hermansky–Pudlak syndrome * Gray platelet syndrome Clotting factor * Hemophilia * A/VIII * B/IX * C/XI * von Willebrand disease * Hypoprothrombinemia/II * Factor VII deficiency * Factor X deficiency * Factor XII deficiency * Factor XIII deficiency * Dysfibrinogenemia * Congenital afibrinogenemia Signs and symptoms * Bleeding * Bruise * Hematoma * Petechia * Purpura * Nonthrombocytopenic purpura By site * head * Epistaxis * Hemoptysis * Intracranial hemorrhage * Hyphema * Subconjunctival hemorrhage * torso * Hemothorax * Hemopericardium * Pulmonary hematoma * abdomen * Gastrointestinal bleeding * Hemobilia * Hemoperitoneum * Hematocele * Hematosalpinx * joint * Hemarthrosis *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Activated protein C resistance

c1861171

wikipedia

https://en.wikipedia.org/wiki/Activated_protein_C_resistance

{"mesh": ["D020016", "C566056"], "umls": ["C1861171"], "icd-9": ["289.81"], "wikidata": ["Q296104"]}

Sialectasis (also termed sialectasia, or siadochiectasis)[1] is cystic dilation of the ducts of salivary glands.[2] It may be caused by salivary duct strictures or stones (sialolithiasis).[3] It can also rarely be congenital.[4] ## See also[edit] * Bronchiectasis ## References[edit] 1. ^ "Radiopedia". 2. ^ Yousem DM; Grossman RI (2010). Neuroradiology: The Requisites. Elsevier Health Sciences. p. 480. ISBN 0-323-04521-9. 3. ^ "Patient.UK". 4. ^ Miziara, ID; Campelo, VE (2005). "Infantile recurrent parotitis: follow up study of five cases and literature review". Brazilian journal of otorhinolaryngology. 71 (5): 570–5. PMID 16612516. * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase *[HAART]: highly active antiretroviral therapy *[Ki]: Inhibitor constant *[nM]: nanomolars *[MOR]: μ-opioid receptor *[DOR]: δ-opioid receptor *[KOR]: κ-opioid receptor *[SERT]: Serotonin transporter *[NET]: Norepinephrine transporter *[NMDAR]: N-Methyl-D-aspartate receptor *[M:D:K]: μ-receptor:δ-receptor:κ-receptor *[ND]: No data *[NOP]: Nociceptin receptor *[BMI]: body mass index

Sialectasis

c0266996

wikipedia

https://en.wikipedia.org/wiki/Sialectasis

{"umls": ["C0266996"], "wikidata": ["Q25339405"]}