TaoMedAI/RareMedData huggingface dataset:
Haim-Munk syndrome (ORPHA:2342)
Haim-Munk syndrome (HMS) is characterized by palmoplantar hyperkeratosis, severe early-onset periodontitis, onychogryposis, pes planus, arachnodactyly and acroosteolysis.
Epidemiology
HMS is rare with less than 100 cases reported in the literature so far. The majority of reported cases are descendants of a few consanguineous families from a religious isolate in Cochin, India. One unrelated Brazilian patient has also been reported.
Clinical description
HMS presents with severe and extensive skin manifestations. In addition to the marked palmoplantar keratosis, patients have scaly erythematous and circumscribed patches on the elbows, knees, forearms, shins and dorsum of the hands. Severe, early-onset progressive periodontitis that affects both the deciduous and permanent dentitions and presents with gingival inflammation and alveolar bone destruction is a hallmark of the disease. Onychogryposis, arachnodactyly, acroosteolysis and pes planus are additional features that help to distinguish HMS from other forms of palmoplantar hyperkeratosis. A peculiar deformity of the fingers (tapered, pointed phalangeal ends and a claw-like volar curve) is typical. Destructive arthritis of the wrist and shoulder joints has been reported in isolated cases. Patients with HMS have increased susceptibility to infections.
Etiology
HMS is caused by germline mutations in the lysosomal protease cathepsin C (CTSC) gene mapped to chromosome 11q14.1-q14.3. Mutations in the same gene cause the clinically related disorders Papillon-Lefèvre syndrome (PLS) and prepubertal periodontitis (see these terms).
Diagnostic methods
Diagnosis is clinical but can be confirmed by detection of the disease-causing mutation.
Differential diagnosis
Differential diagnosis includes the allelic disorder PLS and disorders with palmoplantar hyperkeratosis and prepubertal periodontitis.
Genetic counseling
HMS is transmitted as an autosomal recessive trait.
Management and treatment
Management of the skin manifestations requires topical emollients, keratolytics (including salicylic acid and urea) and oral retinoids (acitretin, etretinate, and isotretinoin). Periodontitis in HMC is usually unresponsive to traditional periodontal therapies. Patients may benefit from extraction of the primary teeth combined with oral antibiotics and professional tooth cleaning. Synovectomy has been shown to alleviate the inflammation associated with destructive arthritis but may lead to loss in the range of the joint motion.

                            Last update: 
                            November 2008


                            - Expert reviewer(s): 
                            Pr Agnès BLOCH-ZUPAN
Hall-Riggs syndrome (ORPHA:2107)
Hall-Riggs syndrome is a very rare syndrome consisting of microcephaly with facial dysmorphism, spondylometaepiphyseal dysplasia and severe intellectual deficit.
Epidemiology
Eight cases have been reported in the literature in two unrelated families.
Clinical description
Dysmorphic features include hypertelorism, depressed nasal bridge, large nose with a large nasal tip, anteverted nostrils and wide mouth with thick lips. Affected patients do not achieve language ability.
Genetic counseling
The condition is probably hereditary, and transmitted as an autosomal recessive trait.

                            Last update: 
                            January 2010
Hallermann-Streiff syndrome (ORPHA:2108)
Hallermann-Streiff syndrome is a rare genetic syndrome characterized mainly by head and facial abnormalities such as bird-like facies (with beak-shaped nose and retrognathia), hypoplastic mandible, brachycephaly with frontal bossing, dental abnormalities (e.g. absence of teeth, natal teeth, supernumerary teeth, severe agenesis of permanent teeth, enamel hypoplasia) hypotrichosis, various ophthalmic disorders (e.g. congenital cataracts, bilateral microphthalmia, ptosis, nystagmus) and atrophy of skin (especially around the center of face and nose) as well as telangiectasia and proportionate short stature. Intellectual disability is reported in some cases.
Hallermann-Streiff-like syndrome (ORPHA:2109)
A rare genetic bone development disorder characterized by multiple congenital fractures, slender ribs and long bones, deficient ossification of the skull, and dysmorphic facial features reminiscent of Hallermann-Streiff syndrome (such as high forehead and triangular face with small jaw, deep-set eyes, beaked, narrow nose, downturned mouth, and posteriorly angulated ears). Bilateral microphthalmia, cataracts, and pulmonary hypoplasia have also been reported. The disease is fatal in the neonatal period. There have been no further descriptions in the literature since 1995.
Hallux varus-preaxial polysyndactyly syndrome (ORPHA:2110)
Hallux varus-preaxial polysyndactyly syndrome is a rare, genetic, congenital limb malformation disorder characterized by bilateral medial displacement of the hallux and preaxial polysyndactyly of the first toes. Radiographs show broad, shortened, misshapen first metatarsals and may associate incomplete or complete duplication of proximal phalanges and duplication or triplication of distal phalanges. There have been no further descriptions in the literature since 1980.
Hamel cerebro-palato-cardiac syndrome (ORPHA:93946)
An X-linked intellectual disability syndrome (XLMR) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome.
Epidemiology
The prevalence is unknown. It has been reported in a family with 2 brothers and their 2 maternal uncles who presented with severe intellectual deficiency.
Clinical description
Marked facial characteristics (abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, small mouth, and micrognathia), cleft or highly arched palate, and atrial septal defects were observed. Three out of four patients died in infancy or early childhood. Hamel cerebro-palato-cardiac syndrome represents the more severe phenotypic variant.
Etiology
The syndrome is caused by mutations in the PQBP1 gene. Expansions or reductions in the DR/ER repeat in the polar-amino-acid-rich domain (PRD) are responsible for a truncated protein that is thought to disrupt polyglutamine binding.
Genetic counseling
Hamel cerebro-palato-cardiac syndrome follows an X-linked recessive pattern of inheritance. Genetic testing is possible to identify carrier females and to inform them of the risk of passing on the gene to their offspring.

                            Last update: 
                            June 2012


                            - Expert reviewer(s): 
                            Pr Vincent DES PORTES
Hand-foot-genital syndrome (ORPHA:2438)
Hand-foot-genital syndrome (HFGS) is a very rare multiple congenital abnormality syndrome characterized by distal limb malformations and urogenital defects.
Hantavirus pulmonary syndrome (ORPHA:319247)
A rare viral hemorrhagic fever characterized by virus-induced microvascular leakage rapidly leading to a severe illness with diffuse pulmonary edema and respiratory failure. These symptoms set in after a short first disease stage with fever, myalgia, and headache, followed by severe gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea. The high lethality of the disease is due to the possible development of hypotension and cardiogenic shock.
Hao-Fountain syndrome due to 16p13.2 microdeletion (ORPHA:500055)
A partial deletion of the short arm of chromosome 16 characterized by developmental delay, intellectual disability, speech delay, autism spectrum disorder, epilepsy, hypogonadism, and hypotonia. The behavioral profile includes impulsivity, compulsivity, stubbornness, manipulative behaviors, temper tantrums, and aggressive behaviors.
Hardikar syndrome (ORPHA:1415)
A rare multiple congenital malformation syndrome, characterized by an association of cleft lip and palate, patchy pigmentary retinopathy (cat's paw), obstructive liver disease (cholestasis, portal hypertension etc.) and obstructive renal disease (ectopic ureteric insertion, obstruction, vesicouretral reflux and hydronephrosis). Gastrointestinal tract involvement (malrotation, gastresophageal reflux etc.) and cardiac involvement (coarctation of aorta, pulmonary artery stenosis, etc.) have also been reported. An overlap with Kabuki syndrome is debated.
Harlequin syndrome (ORPHA:199282)
Harlequin syndrome (HSD) is an autonomic disorder occurring at any age and characterized by unilateral flushing and sweating, involving the face and sometimes arm and chest, in condition of thermal, exercise or emotional stress without sympathetic ocular manifestations. However, tonic pupils, parasympathetic oculomotor lesion and pre- or postganglionic sudomotor sympathetic deficit can rarely occur.
Harrod syndrome (ORPHA:2115)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by the association of intellectual deficit, facial dysmorphism (a highly arched palate, pointed chin, and small mouth, hypotelorism, a long nose and large protruding ears), arachnodactyly, hypogenitalism (undescended testes and hypospadias) and failure to thrive.
Hartnup disease (ORPHA:2116)
A rare metabolic disorder belonging to the neutral aminoacidurias, mainly characterized by skin photosensitivity, ocular and neuropsychiatric features, due to abnormal renal and gastrointestinal transport of neutral amino acids (tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine and valine).
Epidemiology
The estimated prevalence is approximately 1 in 30,000.
Clinical description
Most subjects who fulfil the biochemical diagnostic criteria (mostly detected by newborn screening programs) remain asymptomatic. In the few symptomatic subjects, clinical symptoms usually appear in childhood (3-9 years of age), but sometimes manifest as early as 10 days after birth, or as late as early adulthood. Symptomatic subjects usually present with skin photosensitivity (pellagra-like skin eruption), neurological symptoms (intermittent cerebellar ataxia, spasticity, delayed motor development, trembling, headaches, and hypotonia), and psychiatric symptoms (anxiety, emotional instability, delusions, and hallucinations). Ocular manifestations may occur (double vision, nystagmus, photophobia, and strabismus). Intellectual deficit and short stature have been described in a few patients. Exacerbations are seen most frequently in the spring or early summer after sunlight exposure. Symptoms may also be triggered by fever, drugs, and emotional or physical stress. They progress over several days and last for 1-4 weeks before spontaneous remission occurs.
Etiology
Hartnup disease is caused by mutations in SLC6A19 gene (5p15.33), encoding the sodium-dependent and chloride-independent neutral amino acid transporter B(0)AT1, expressed predominately in proximal renal tubules and intestinal epithelium.
Diagnostic methods
Neutral hyperaminoaciduria (determined by urine chromatography) is the diagnostic hallmark. Diagnostic confirmation relies upon the mutation analysis of the SLCA19 gene (broad allelic heterogeneity).
Differential diagnosis
Pellagra is the main differential diagnosis. Blue diaper syndrome, ataxia-telangiectasia, hydroa vacciniforme, pityriasis alba, and xeroderma pigmentosum should be excluded.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Symptomatic subjects benefit from a high-protein diet, sunlight protection, and avoidance of photosensitizing drugs. Treatment includes nicotinamide supplements (40 to 200 mg per day). Some patients may respond to a tryptophan-rich diet. Patients with severe central nervous system involvement require neurologic and psychiatric treatment.
Prognosis
The presentation of the disorder is commonly benign. Hartnup disease probably does not adversely affect pregnancy and would be harmless to the fetus.

                            Last update: 
                            July 2019


                            - Expert reviewer(s): 
                            Pr Udo WENDEL
Hawkinsinuria (ORPHA:2118)
A rare inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin ((2-l-cystein-S-yl, 4-dihydroxycyclohex-5-en-1-yl)acetic acid), in the urine.
Hearing loss-familial salivary gland insensitivity to aldosterone syndrome (ORPHA:3225)
Hearing loss-familial salivary gland insensitivity to aldosterone syndrome is characterised by bilateral moderate-to-severe sensorineural hearing loss and salivary gland insensitivity to aldosterone resulting in hyponatremia. It has been described in two brothers. Transmission appeared to be autosomal recessive.
Heart defect-tongue hamartoma-polysyndactyly syndrome (ORPHA:1338)
A rare, genetic, multiple congenital anomalies syndrome characterized by congenital heart defects (e.g. coarctation of the aorta with or without atrioventricular canal and subaortic stenosis), associated with tongue hamartomas, postaxial hand polydactyly and toe syndactyly.
Heart defects-limb shortening syndrome (ORPHA:1354)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by skeletal dysplasia (including coronal clefting of the vertebral bodies and short limbs and variable congenital heart malformations, such as atrial and ventricular septal defects, right ventricular hypoplasia, and valve defects). There have been no further descriptions in the literature since 1990.
Heart-hand syndrome type 2 (ORPHA:1350)
Heart-hand syndrome type 2 is an extremely rare heart-hand syndrome (see this term) described in two families to date, that is characterized by upper limb malformations (brachytelephalangy type D, hypoplastic deltoids, mild shortening of the fourth and fifth metacarpals in some individuals, skeletal anomalies in the humerus, radius, ulnae, and thenar bones) and cardiac arrhythmias (junctional rhythms and atrial fibrillation).
Heart-hand syndrome type 3 (ORPHA:1342)
Heart-hand syndrome type 3 is a very rare heart-hand syndrome (see this term), described in three members of a Spanish family to date, which is characterized by a cardiac conduction defect (sick sinus, bundle-branch block) and brachydactyly, resembling brachydactyly type C of the hands (see this term), affecting principally the middle phalanges in conjunction with an extra ossicle on the proximal phalanx of both index fingers. Feet abnormalities are more subtle.
Heart-hand syndrome, Slovenian type (ORPHA:168796)
A rare autosomal dominant form of heart-hand syndrome that is characterized by adult onset, progressive cardiac conduction disease, tachyarrhythmias that can lead to sudden death, dilated cardiomyopathy and brachydactyly, with the hands less severely affected than the feet. Muscle weakness and/or myopathic electromyographic findings have been observed in some cases.
Heart-hand syndrome (ORPHA:228184)
Heart-hand syndrome refers to a group of congenital disorders characterized by malformations of the upper limbs and heart. To date, heart-hand syndrome comprises the following rare syndromes; Holt-Oram syndrome; heart-hand syndrome type 2; heart-hand syndrome type 3; heart hand syndrome, Slovenian type, brachydactyly-long thumb; and patent ductus arteriosus-bicuspid aortic valve - hand anomalies (see these terms).
Heavy chain deposition disease (ORPHA:93556)
A rare non-amyloid monoclonal immunoglobulin deposition disease characterized by production of monoclonal immunoglobulins with truncated heavy chains and no detectable light chains, which are deposited in tissues and cause organ dysfunction, but do not form amyloid beta-pleated sheets or contain an amyloid P component. The condition frequently occurs in association with multiple myeloma. Patients most commonly present with renal involvement (manifesting as hypertension, progressive renal dysfunction, anemia, and nephrotic syndrome with microhematuria), but other organs (such as the liver or skin) may also be affected. Production of IgG1 or IgG3 isotypes results in hypercomplementemia.
Heavy chain disease (ORPHA:86864)
Heavy-chain diseases (HCDs) are rare monoclonal lymphoplasma-cell proliferative disorders involving B cells and are characterized by the synthesis of truncated heavy chains without associated light chains.
Epidemiology
The prevalence is unknown.
Clinical description
HCDs have been described for the three main immunoglobulin classes: alpha-HCD (see this term) is the most common and has the most uniform presentation whereas gamma- and mu-HCDs (see these terms) have variable clinical presentations and histopathologic features. HCDs can be thought of as variant types of non-Hodgkin lymphoma (NHL; see this term), with alpha-HCD presenting as an extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue, gamma-HCD as lymphoplasmacytoid NHL, and mu-HCD as small lymphocytic NHL or chronic lymphocytic leukemia (CLL; see this term).
Diagnostic methods
Diagnosis of these conditions requires documentation of a deleted immunoglobulin heavy chain without a bound light chain in the serum or urine.
Prognosis
Prognosis is variable, and no standardized effective treatment programs are available except for alpha-HCD, which in its early stage may respond to antibiotics.

                            Last update: 
                            October 2011


                            - Expert reviewer(s): 
                            Pr Robert KYLE  - Dr Dietlind WAHNER-ROEDLER
HEC syndrome (ORPHA:2119)
A rare syndromic cardiac disease characterized by communicating hydrocephalus, endocardial fibroelastosis, and congenital cataracts. A history of upper respiratory infection in the mother during the first trimester of pregnancy and polyhydramnios in the third trimester has been associated. No evience of toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and galactosemia is reported. There have been no further descriptions in the literature since 1995.
Heiner syndrome (ORPHA:99932)
Heiner syndrome, also called cow's milk hypersensitivity, is a food induced pulmonary hypersensiting syndrome that affects primarily infants and that is characterized by pulmonary hemosiderosis (see this term), digestive bleeding, anemia and poor growing, improving with elimination of cow's milk from the diet.
Helicoid peripapillary chorioretinal degeneration (ORPHA:86813)
Helicoid peripapillary chorioretinal degeneration is a rare autosomal dominantly inherited chorioretinal degeneration disease, presenting at birth or infancy, characterized by progressive bilateral retinal and choroidal atrophy, appearing as lesions on the optic nerve and peripheral ocular fundus and leading to central vision loss. Congenital anterior polar cataracts are sometimes associated with this disease.
HELLP syndrome (ORPHA:244242)
A rare hemorrhagic disorder due to an acquired platelet anomaly characterized by hemolysis, elevated liver enzymes and thrombocytopenia that affects pregnant or post-partum women, and is frequently associated with severe preeclampsia. Symptoms are variable, typically including right upper quadrant or epigastric abdominal pain, nausea, vomiting, excessive weight gain, generalized edema, hypertension, general malaise, right shoulder pain, backache, and/or headache. Hepatic hemorrhage and rupture, renal failure, and pulmonary edema can result in maternal and/or fetal death.
Hemangioblastoma (ORPHA:252054)
Hemangioblastoma is a rare, benign, highly vascularized tumor of the central nervous system, most often located in the cerebellum or spinal cord, presenting in adulthood and manifesting with dizziness, nausea, malaise, headache, bladder or bowel dysfunction, numbness, weakness and pain in the upper or lower extremities, and often associated with von Hippel-Lindau disease (VHL; see this term). Exceptional cases of hemangioblastoma arising outside of the central nervous system have been reported.
Heme oxygenase-1 deficiency (ORPHA:562509)
A rare inborn error of metabolism characterized by congenital asplenia and childhood or adolescent onset of generalized inflammation, persistent intravascular hemolysis and anemia, severe endothelial injury with abnormal coagulation, bleeding diathesis, and nephropathy. Additional reported manifestations include growth retardation, mild facial dysmorphism, and hepatomegaly.
Hemicrania continua (ORPHA:443070)
A rare trigeminal autonomic cephalalgia characterized by indomethacin-sensitive, persistent, strictly unilateral headache lasting for more than three months, associated with ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis, eyelid edema, and/or restlessness or agitation, and not better accounted for by another type of headache. Migrainous symptoms such as photophobia are often observed. The headache may be continuous (unremitting subtype) or interrupted by remission periods of more than 24 hours (remitting subtype).
Hemidystonia-hemiatrophy syndrome (ORPHA:306741)
Hemidystonia-hemiatrophy (HD-HA) is a rare dystonia, usually caused by a static cerebral injury occurring at birth or during infancy, that is characterized by a combination of hemidystonia (HD), involving one half of the body, and hemiatrophy (HA) on the same side as the HD.
Epidemiology
The prevalence is unknown but between 30 to 100 cases of HD-HA have been described to date.
Clinical description
The mean age of HD onset is 14.9 years (range 1-46 years). HD (sustained and repetitive muscle contractions resulting in abnormal movements or posture involving a single side of the body) is preceded in 90 % of cases by hemiparesis with a marked improvement before the onset of HD. Pyramidal syndrome and seizures may also be observed. In HD-HA, dystonia is associated with ipsilateral somatic atrophy.
Etiology
Common causes of HD-HA are childbirth or perinatal complications, delayed sequelae of stroke or head trauma. The causative injury generally occurs at birth or during early infancy.
Diagnostic methods
Diagnosis of HD-HA is clinical, based on a careful anamnesis of the patient's birth and early childhood period and physical examinations, as well as brain imaging. Cerebral hemiatrophy, nonspecific diffuse atrophy, lesions involving the basal ganglia and thinning of the periventricular white matter with ipsilateral ventricular dilatation may be observed with magnetic resonance imaging (MRI). Brain imaging is characterized by lesions involving the basal ganglia or by cerebral hemiatrophy contralateral to the HD. Cerebral HA can lead to ipsilateral skull thickening and hyperpneumatization of paranasal sinuses, resulting in Dyke-Davidoff syndrome.
Differential diagnosis
HD-HA syndrome should be differentiated from other causes of primary dystonia or dystonia secondary to inherited disorders or neurodegenerative diseases.
Management and treatment
HD responds poorly to medical therapy and drugs such as anticholinergics, baclofen, benzodiazepines, and levodopa, in monotherapy or in combination, result in a modest or transient response. Botulinum toxin injections may be useful for HD if a relevant focal target can be identified. Deep brain stimulation mainly targeting the globus pallidus is not a routine treatment of HD-HA syndrome, but may be discussed in the most severe cases on an individual basis.
Prognosis
The younger the age of the offending cerebral insult, the longer is the delay in the onset of dystonia. The symptoms of delayed HD usually diminish and attain a plateau a few years after initial presentation; while HA of the affected body part usually remains stationary as the patient approaches the second decade of life.

                            Last update: 
                            March 2014


                            - Expert reviewer(s): 
                            Dr David GRABLI