TaoMedAI/RareMedData huggingface dataset:
Hereditary sensory and autonomic neuropathy type 5 (ORPHA:64752)
A disorder that is characterized by loss of pain perception and impaired temperature sensitivity, in the absence of any other major neurological anomalies.
Epidemiology
Prevalence is unknown. Only a small number of cases have been described in the literature, although one large multigenerational consanguineous family from northern Sweden has been reported.
Clinical description
Other findings include ulcers, self-mutilation and damaged joints. Intelligence is normal.
Etiology
Mutations in the NGF gene (1p13.1) were detected in affected members of the large Swedish family. However, mutations in the NTRK1 gene (1q21-q22) have been identified in one patient diagnosed with HSAN5 with the additional finding of mild anhidrosis. Mutations in the NTRK1 gene have also been implicated in the more severe HSAN subform, HSAN4 (congenital insensitivity to pain with anhidrosis; see this term).
Genetic counseling
The syndrome is transmitted in an autosomal recessive manner

                            Last update: 
                            January 2009
Hereditary sensory and autonomic neuropathy type 6 (ORPHA:314381)
A rare hereditary sensory and autonomic neuropathy characterized by hypotonia in infancy, variable psychomotor retardation, markedly impaired pain sensitivity with poorly healing distal ulcerations and painless fractures leading to joint deformities and amputation of fingers and toes, altered deep tendon reflexes, and dysautonomic symptoms including hypohidrosis and heat intolerance, chronic diarrhea, pupillary abnormalities, or urinary incontinence. Sensorineural hearing loss has also been reported. The severity of the disease is highly variable, with severe cases being potentially lethal in infancy.
Hereditary sensory and autonomic neuropathy type 7 (ORPHA:391397)
A rare, genetic, periphery neuropathy characterized by a congenital insensitivity to pain, muscular hypotonia and gastrointestinal disturbances. Patients present with delayed motor milestones achievement, self-mutilations, skin ulcers, poor wound healing, painless fractures, hyperhidrosis, abdominal discomfort, diarrhea and/or constipation. Cognitive development is normal.
Hereditary sensory and autonomic neuropathy type 8 (ORPHA:478664)
A rare autosomal recessive hereditary sensory and autonomic neuropathy characterized by congenital impaired sensation of acute or inflammatory pain in combination with an inability to identify noxious heat or cold, leading to numerous painless mutilating lesions and injuries. Further manifestations are absence of corneal reflexes resulting in corneal scarring, reduced sweating and tearing, and recurrent skin infections. Large-fiber sensory modalities such as light touch, vibration, and proprioception are normal.
Hereditary sensory and autonomic neuropathy with deafness and global delay (ORPHA:139573)
This syndrome is characterized by a sensory and autonomic axonal neuropathy, sensorineural hearing loss and persistent global developmental delay.
Epidemiology
It has been described in four individuals from a consanguineous Lebanese family.
Clinical description
Onset occurred in infancy with moderate developmental delay, hypotonia and areflexia. Other less constant findings included weakness, variable dysmorphic features, unsteadiness, and optic atrophy.
Genetic counseling
Transmission appears to be autosomal recessive.

                            Last update: 
                            January 2009
Hereditary sensory neuropathy-deafness-dementia syndrome (ORPHA:456318)
A rare genetic neurological disorder characterized by sensorineural hearing loss, sensory neuropathy, behavioral abnormalities, and dementia. Occurrence of seizures has also been reported. Age of onset is between adolescence and adulthood. The disease is progressive, with fatal outcome typically in the fifth to sixth decade.
Hereditary sodium channelopathy-related small fibers neuropathy (ORPHA:306577)
A rare, genetic, peripheral neuropathy disorder due to gain-of-function mutations in voltage-gated sodium channels present in the small peripheral nerve fibers characterized by neuropathic pain of varying intensity (often beginning in the distal extermities and with a burning quality) associated with autonomic dysfunction (e.g. orthostatic dizziness, palpitations, dry eyes and mouth), abnormal quantitative sensory testing, and reduction in intraepidermal nerve ﬁber density. Large fiber functions (i.e. normal strength, tendon reflexes, and vibration sense) and nerve conduction studies are typically normal.
Hereditary thermosensitive neuropathy (ORPHA:84093)
Hereditary thermosensitive neuropathy is a rare, demyelinating, hereditary motor and sensory neuropathy characterized by reversible episodes of ascending muscle weakness, paresthesias and areflexia triggered by a febrile episode, with or without pressure palsy.
Hereditary thrombocytopenia with early-onset myelofibrosis (ORPHA:480851)
A rare syndromic constitutional thrombocytopenia characterized by thrombocytopenia with increased bleeding tendency (leading to epistaxis, menorrhagia, and petechiae), in combination with myelofibrosis and splenomegaly. Platelets may be abnormally large or small and partly hypo- or agranular, plasma thrombopoietin is elevated, and the number of megakaryocytes in the bone marrow increased. Additional non-hematologic manifestations have been described in some patients, including mild bone abnormalities and facial dysmorphism with large forehead, hypertelorism, deep-set eyes, and wide nostrils.
Hereditary thrombocytopenia with normal platelets (ORPHA:268322)
A rare, genetic, isolated constitutional thrombocytopenia disease characterized by decreased platelet counts, not associated with platelet morphology or function impairment, in multiple members of a family. Manifestations are variable, typically ranging from asymptomatic to mild bleeding diathesis (e.g. easy bruising, epistaxis, petechiae). Occasionally, a more severe bleeding tendency has been associated and a mild predisposition to infection and eczema has been reported.
Hereditary thrombophilia due to congenital antithrombin deficiency (ORPHA:82)
Hereditary thrombophilia due to congenital antithrombin deficiency is a rare, genetic, hematological disease characterized by decreased levels of antithrombin activity in plasma resulting in impaired inactivation of thrombin and factor Xa. Patients have an increased risk for venous thromboembolism, usually in the deep veins of the arms, legs and pulmonary system and, on occasion, in other venous territories (e.g. cerebral veins or sinus, mesenteric, portal, hepatic, renal and/or retinal veins).
Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency (ORPHA:217467)
A rare, genetic, coagulation disorder characterized by a tendency to develop thrombosis, resulting from decreased histidine-rich glycoprotein (HRG) plasma levels. Manifestations are variable depending on location of thrombosis, but may include headaches, diplopia, progressive pain, limb swelling, itching or ulceration, and brownish skin discoloration, among others.
Heritable pulmonary arterial hypertension (ORPHA:275777)
Heritable pulmonary arterial hypertension (HPAH) is a form of pulmonary arterial hypertension (PAH, see this term), occurring due to mutations in PAH predisposing genes or in a familial context. HPAH is characterized by elevated pulmonary arterial resistance leading to right heart failure. HPAH is progressive and potentially fatal.
Epidemiology
HPAH represent less than 4% of PAH. Prevalence is estimated at < 1/million people.
Clinical description
HPAH develop usually in adults, and rarely in children; women are twice as likely as men to be affected. Usual age at diagnosis is mid thirties. Initial symptoms include dyspnea, fatigue, syncope, chest pain, palpitations and pedal edema. Precordial signs include loud and palpable second heart sound, right ventricular heave, pulmonary ejection click and murmurs of pulmonary and tricuspid regurgitation.70% of patients present heart failure (classed as New York heart association functional classification (NYHA FC) III or IV).Rarely, clubbing and Raynaud phenomenon (mostly in females) have been observed. Hemoptysis has also been reported. HPAH patients have a severe clinical with less response to acute vasodilator challenge, lower cardiac index, and higher pulmonary vascular resistance. HPAH due to ACVRL1or TBX4gene mutations occurs more commonly in children with rapid progression and poor prognosis.
Etiology
HPAH has been linked to mutations in BMPR2 ((2q33) in majority of cases. However, other genes implicated in HPAH have been described in few cases, and include ACVRL1 ((12q13)), KCNK3 (2p23),CAV1(7q31), TBX4 (17q21) and SMAD9(13q12) .
Genetic counseling
Patients displaying a sporadic PAH or a PAH occurring in a familial context, should be tested in priority for mutations in BMPR2 gene. If no mutations in BMPR2gene were identified in a patient displaying a familial form of PAH, mutations in all other PAH predisposing genes have to searched successively. All PAH predisposing genes are transmitted in an autosomal dominant manner with an incomplete penetrance. In the cases ofBMPR2 mutations the penetrance is estimated to be 42% in female mutation carriers and 14% in male mutation carriers. Prenatal genetic testing and preimplantation diagnosis are considered in patients and asymptomatic relatives carriers of a mutation in PAH predisposing genes.

                            Last update: 
                            January 2015


                            - Expert reviewer(s): 
                            Dr Barbara GIRERD  - Pr David MONTANI
Hermansky-Pudlak syndrome due to BLOC-2 deficiency (ORPHA:231512)
Hermansky-Pudlak syndrome without pulmonary fibrosis as a complication includes three relatively mild types (HPS-3, HPS-5 and HPS-6) of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by ocular or oculocutaneous albinism, bleeding diathesis and, in some cases, granulomatous colitis.
Epidemiology
HPS-3 occurs as a genetic isolate in central Puerto Rico with a prevalence of 1/4000; additionally, around 15 non-Puerto-Rican cases of HPS-3 have been reported. Ten cases of HPS-5 have been reported and 25 cases of HPS-6, from which 20 come from an Israeli-Bedouin tribe.
Clinical description
These three types present with features of HPS including ocular or oculocutaneous albinisim, reduced visual acuity, horizontal nystagmus, easy bruising of soft tissues, epistaxis, and prolonged bleeding after dental extraction, surgery or childbirth. Women may present with medically significant menstrual bleeding. Complications of HPS may include reduced renal function and granulomatous colitis. Pulmonary fibrosis has not been found to develop in HPS-3, HPS-5 or HPS-6. The course of HPS with no pulmonary involvement is mild.
Etiology
HPS-3 is caused by mutations in the HPS3 gene (3q24), HPS-5 is caused by mutations in the HPS5 gene (11p15-p13) and HPS-6 is caused by mutations in the HPS6 gene (10q24.32). The gene products, HPS3, HPS5 and HPS6, are part of the multi-subunit complex BLOC-2 (biogenesis of lysosome-related organelles complex 2).
Genetic counseling
Transmission is autosomal recessive.

                            Last update: 
                            March 2010


                            - Expert reviewer(s): 
                            Dr William GAHL  - Dr Marjan HUIZING
Hermansky-Pudlak syndrome due to BLOC-3 deficiency (ORPHA:231500)
Hermansky-Pudlak syndrome with pulmonary fibrosis as a complication includes two types (HPS-1 and HPS-4) of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and, in some cases, pulmonary fibrosis or granulomatous colitis.
Epidemiology
Prevalence of all types of HPS is estimated at between 1/500,000 and 1/1,000,000 in non-Puerto Rican populations. In northwestern Puerto Rico the prevalence of HSP-1 is 1/1,800 due to a founder effect. HSP-1 is reported in sporadic patients worldwide; founder effects have (apart from Puerto Rico) also been reported in a small isolate in a Swiss village and in Japan. Prevalence of HSP-4 is unknown, but to date around 20 patients have been described worldwide.
Clinical description
HPS-1 and HPS-4 present with features of HPS including oculocutaneous albinisim, reduced visual acuity, horizontal nystagmus, easy bruising of soft tissues, epistaxis, and prolonged bleeding after dental extraction, surgery or childbirth. Women may present with medically significant menstrual bleeding. Complications of HPS may include granulomatous colitis and pulmonary fibrosis. Pulmonary fibrosis is the most serious complication of HPS-1 and HPS-4 and usually presents in the fourth or fifth decade.
Etiology
HPS-1 is caused by mutations in the HPS1 gene (10q23.1) and HPS-4 is caused by mutations in the HPS4 gene (22q11.2-q12.2). The gene products, HPS1 and HPS4, are part of the multi-subunit complex BLOC-3 (biogenesis of lysosome-related organelles complex 3).
Genetic counseling
HPS1 and HPS4 are both transmitted in an autosomal recessive manner.
Management and treatment
Lung transplant is the only known treatment for pulmonary fibrosis in HPS-1 and HPS-4. Pirfenidone may slow progression but only in patients who have significant residual lung function. Steroid therapy is not effective.
Prognosis
Prognosis is poor as the pulmonary fibrosis is fatal.

                            Last update: 
                            March 2010


                            - Expert reviewer(s): 
                            Dr William GAHL  - Dr Marjan HUIZING
Hernández-Aguirre Negrete syndrome (ORPHA:2139)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, mild intellectual disability, seizures, obesity, and dysmorphic facial features (including large, bulbous nose, prominent philtrum, wide mouth). Additional reported features are bilateral pes planus, scoliosis, and spina bifida occulta. Brain MRI may show mild ventricular dilatation.
Herpes simplex virus stromal keratitis (ORPHA:137599)
Herpes simplex (HSV) stromal keratitis is an infectious ocular disease of either necrotizing or non-necrotizing form, due to an HSV infection, and characterized by corneal stromal necrosis, inflammation, ulceration and infiltration by leukocytes. Corneal perforation and blindness can also occur in severe cases.
Herpetiform pemphigus (ORPHA:208524)
A rare superficial pemphigus disease characterized by severe intractable pruritus with erythematous or urticarial plaques and sometimes vesicles organized in a herpetiform pattern. Mucosae are generally spared. Eosinophilia in peripheral blood and low titers of circulating autoantibodies are observed in many cases. Histology can show an aspect of either pemphigus (superficial or deep), or an intraepidermal infiltrate rich in eosinophils (eosinophilic spongiosis).
HIDEA syndrome (ORPHA:436141)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by profound intellectual disability, hypotonia, coarse facial features, strabismus and impaired visual fixation, hypermobility of interphalangeal joints, contractures in the elbow joints, and pes planovalgus. Seizures and episodes of aggressive behavior during sleep have also been reported.
Hidrotic ectodermal dysplasia, Christianson-Fourie type (ORPHA:1808)
Hidrotic ectodermal dysplasia, Christianson-Fourie type is a rare ectodermal dysplasia syndrome characterized by tricho- and onychodysplasia in association with cardiac rhythm abnormalities. Patients present with sparse scalp hair and eyelashes, absent or sparse eyebrows, dystrophic thickened nails (on fingers distal end may be lifted from the nail bed) and supraventricular tachicardia or sinus bradicardia.
Hidrotic ectodermal dysplasia, Halal type (ORPHA:1809)
Hidrotic ectodermal dysplasia, Halal type is a form of ectodermal dysplasia syndrome (see this term) characterized by trichodysplasia, with absent eyebrows and eyelashes, onychodysplasia, mild retrognathia, abnormal dermatoglyphics (excess of whorls on fingertips, radial loop on finger, hypothenar pattern), intellectual disability and normal teeth and sweating. Additional variable manifestations include high implanted or prominent ears, mild hearing loss, supernumerary nipple, café-au-lait spots, keratosis pilaris, and irregular menses. To date, four individuals from 2 generations of a consanguineous family of Portuguese descent have been described in the literature. Males and females were equally affected. Hidrotic ectodermal dysplasia, Halal type is inherited in an autosomal recessive manner.
Hidrotic ectodermal dysplasia (ORPHA:189)
Clouston syndrome (or hidrotic ectodermal dysplasia) is characterised by the clinical triad of nail dystrophy, alopecia, and palmoplantar hyperkeratosis.
Epidemiology
The disease was first described in the French-Canadian population (in which it is associated with a founder effect), but has since been identified in several other ethnic groups. The exact prevalence is unknown and the syndrome is likely to be underdiagnosed.
Clinical description
Nail abnormalities are the most consistent feature and frequently manifest at birth or in early infancy. The nails are thickened, slow growing, brittle, often hyperconvex and discoloured with striation. Additional reported features include micronychia, onycholysis and recurrent paronychial infections leading to nail loss. Hair involvement manifests at birth or later during infancy or childhood, and ranges from total to partial, often progressive, alopecia. Residual scalp hair is slow growing, sparse, fine and brittle. Eyebrows and eyelashes are also frequently sparse and axillary, pubic and body hair can be affected. Palmoplantar hyperkeratosis is not a constant finding. When present, it usually begins in childhood and tends to worsen with age; some patients also develop hyperkeratosis and hyperpigmentation over the joints and bony prominences. The teeth are usually unaffected and sweating is normal.
Etiology
Clouston syndrome is caused by mutations in the GJB6 gene (13q12), encoding the gap junction protein connexin 30 (Cx30).
Diagnostic methods
Diagnosis may be suspected on the basis of the clinical triad of nail dystrophy, hypotrichosis and hyperkeratosis of the palms and soles. The diagnosis can be confirmed by molecular analysis of the GJB6 gene.
Differential diagnosis
The differential diagnosis should include pachyonychia congenita and other forms of ectodermal dysplasia (see these terms).
Antenatal diagnosis
Prenatal testing is possible in families where the disease-causing mutation has been identified.
Genetic counseling
Clouston syndrome is transmitted as an autosomal dominant trait. Disease penetrance is complete, but expression is quite variable even between affected individuals from the same family.
Management and treatment
At present there is no treatment for the disease and management is purely supportive.
Prognosis
The life-span for patients is normal.

                            Last update: 
                            April 2008


                            - Expert reviewer(s): 
                            Pr Giovanna ZAMBRUNO
High altitude pulmonary edema (ORPHA:330012)
A rare pulmonary condition characterized by non-cardiogenic pulmonary edema occurring in otherwise healthy individuals within days of an ascent above 2500-3000 m. Early symptoms include exertional dyspnea, non-productive cough, chest tightness, and reduced exercise performance, followed by dyspnea at rest and possibly orthopnea, as well as gurgling in the chest and pink frothy sputum in advanced cases. Clinical signs are cyanosis, tachypnea, tachycardia, crackles or wheezing, and elevated body temperature (generally not exceeding 38.5°C). Signs of concomitant high-altitude cerebral edema may also be observed. Chest x-rays typically show patchy opacities predominantly in the right middle lobe.
High bone mass osteogenesis imperfecta (ORPHA:314029)
High bone mass osteogenesis imperfecta is a rare, genetic, primary bone dysplasia disorder characterized by increased bone fragility, manifesting with multiple, childhood-onset, vertebral and peripheral fractures, associated with increased bone mass density on radiometric examination. Patients typically present normal or mild short stature and dentinogenesis, hearing, and sclerae are commonly normal.
High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement (ORPHA:480541)
A rare aggressive B-cell non-Hodgkin lymphoma characterized by a rearrangement in MYC and BCL2 and/or BCL6 (so-called double-hit or triple-hit lymphoma). The category includes double-hit cases with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, blastoid cases with a double-hit, and cases with a DLBCL, not otherwise specified, morphology with a double-hit. It refers only to de novo cases, not to lymphomas with a history of pre-existing or coexistent indolent lymphoma. Patients typically present with widespread disease, including involvement of lymph nodes, bone marrow, and central nervous system.
High myopia-sensorineural deafness syndrome (ORPHA:363396)
High myopia-sensorineural deafness syndrome is a rare genetic disease characterized by high myopia, typically ranging from -6.0 to -11.0 diopters, and moderate to profound, bilateral, progressive sensorineural hearing loss with prelingual-onset. Affected individuals do not present other systemic, ocular or connective tissue manifestations.
High-grade neuroendocrine carcinoma of the cervix uteri (ORPHA:213777)
High-grade neuroendocrine carcinoma of the cervix uteri is a rare, aggressive, primary cervical neoplasm, originating from neuroendocrine cells present in the lining epithelium of the cervix, characterized, macroscopically, by usually large lesions, sometimes with a barrel-shaped appearance. Patients often present with abnormal vaginal bleeding or discharge, pelvic/abdominal pain, post-coital spotting and/or dysuria, while symptoms related to carcinoid syndrome are not frequent.
High-grade neuroendocrine carcinoma of the corpus uteri (ORPHA:213731)
High-grade neuroendocrine carcinoma of the corpus uteri is an extremely rare, aggressive, primary uterine neoplasm, originating from neuroendocrine cells scattered within the endometrium, characterized, macroscopically, by a bulky, frequently polypoid, mass with abundant necrosis located in the uterus and, histologically, by rosette-like and cord-like structures consisting of small, rounded cells with oval nuclei and scarce cytoplasm. Patients often present with dysfunctional uterine bleeding, pelvic or abdominal mass and, especially in later stages of the disease, abdominal pain. Symptomatic metastatic spread or symptoms related to a paraneoplastic syndrome, such as retinopathy, or Cushing syndrome due to ectopic ACTH production, may be associated.
Hip dysplasia, Beukes type (ORPHA:2114)
A primary bone dysplasia, characterized by premature degenerative arthropathy of the hip. The disease presents with hip joint discomfort/pain and gait disturbances that usually develop in childhood and that progress to severe functional disability and limited mobility by early adulthood. Involvement of the vertebral bodies and other joints is minimal, height is not significantly reduced, and general health is unimpaired. Radiographically, the femoral heads are flattened and irregular and degenerative osteoarthritis develops in the hip joints, as evidenced by the presence of periarticular cysts, sclerosis, and joint space narrowing.
Hirschsprung disease-deafness-polydactyly syndrome (ORPHA:2155)
Hirschsprung disease-deafness-polydactyly syndrome is an extremely rare malformative association, described in only two siblings to date, characterized by Hirschsprung disease (defined by the presence of an aganglionic segment of variable extent in the terminal part of the colon that leads to symptoms of intestinal obstruction, including constipation and abdominal distension), polydactyly of hands and/or feet, unilateral renal agenesis, hypertelorism and congenital deafness. There have been no further descriptions in the literature since 1988.