TaoMedAI/RareMedData huggingface dataset:
Hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome (ORPHA:293967)
Hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome is a rare, non-acquired pituitary hormone deficiency syndrome characterized by severe, congenital microcephaly, facial dysmorphism (highly arched eyebrows, hypertelorism, convex nasal ridge, protruding ears with underdeveloped superior antihelix crus, micrognathia), bilateral sensorineural deafness and hypogonadotropic hypogonadism, in association with early feeding problems, myopia, moderate intellectual disability and moderate short stature.
Hypohidrosis-electrolyte imbalance-lacrimal gland dysfunction-ichthyosis-xerostomia syndrome (ORPHA:528105)
A rare genetic disease characterized by abnormalities in renal ion transport, ectodermal gland homeostasis, and epidermal integrity, resulting in generalized hypohidrosis, heat intolerance, salt-losing nephropathy, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. Development of nephrolithiasis and severe enamel wear have also been described. Laboratory findings include hypermagnesemia, hypokalemia, hypercalcemia, and hypocalciuria.
Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (ORPHA:363523)
Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by severe intellectual disability with significant speech and language impairment, hypohydrosis (often resulting in hyperthermia) with normal sweat gland appearance, tooth enamel hypoplasia, palmoplantar hyperkeratosis and a high frequency of acquired microcephaly. Mild facial dysmorphism, including lateral flaring of the eyebrows, broad nasal tip, and thick vermilion border, may also be observed.
Hypohidrotic ectodermal dysplasia with immunodeficiency (ORPHA:98813)
A rare ectodermal dysplasia syndrome characterized by signs of ectodermal dysplasia (sparse hair, abnormal or missing teeth, decrease or absent sudation), typical facial features (protruding forehead, wrinkles under the eyes, characteristic periorbital hyperpigmentation), and immunodeficiency.
Epidemiology
Prevalence is not known. The incidence is approximately 1/250,000 live male births for the X-linked form. Fewer than 10 patients with the autosomal-dominant form have been reported.
Clinical description
The clinical picture is variable. Typical signs of HED may be observed, such as sparse hair (atrichosis/ hypotrichosis), abnormal (e.g. conical) or missing teeth (anodontia/ hypodontia), decreased or absent sudation due to a lack of sweat glands (anhidrosis/ hypohidrosis), and typical facial features (protruding forehead, wrinkles under the eyes, characteristic periorbital hyperpigmentation) which are associated with immunologic defects such as susceptibility to opportunistic infections, hypogammaglobulinemia, impaired antibody response to polysaccharides or impaired NK-cell activity. Many patients fail to thrive. Ectodermal dysplasia-related symptoms of HED-ID, however, tend to be milder than in patients with other forms of HED. The disease can also be associated with osteopetrosis and lymphedema (hypohidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, lymphedema; see this term).
Etiology
HED-ID is caused by hypomorphic mutations in the coding region of the IKBKG (or NEMO) gene (Xq28) or, less often, mutations in the NFKBIA gene (14q13), both involved in NF-κB activation.
Genetic counseling
Transmission is X-linked recessive in case of IKBKG mutations and autosomal-dominant in case of NFKBIA mutations. Somatic mosaicism seems to occur frequently in HED-ID patients.

                            Last update: 
                            April 2013


                            - Expert reviewer(s): 
                            Pr Holm SCHNEIDER
Hypohidrotic ectodermal dysplasia-hypothyroidism-ciliary dyskinesia syndrome (ORPHA:1882)
A rare, genetic, ectodermal dysplasia syndrome characterized by the association of hypohidrotic ectodermal dysplasia (manifesting with the triad of hypohidrosis, anodontia/hypodontia and hypotrichosis) with primary hypothyroidism and respiratory tract ciliary dyskinesia. Patients frequently present urticaria pigmentosa-like skin pigmentation, increased mast cells and melanin depositions in the dermis and severe, recurrent chest infections. There have been no further descriptions in the literature since 1986.
Hypoinsulinemic hypoglycemia and body hemihypertrophy (ORPHA:293964)
Hypoinsulinemic hypoglycemia and body hemihypertrophy is a rare, genetic, endocrine disease characterized by neonatal macrosomia, asymmetrical overgrowth (typically manifesting as left-sided hemihypertrophy) and recurrent, severe hypoinsulinemic (or hypoketotic hypo-fatty-acidemic) hypoglycemia in infancy, which results in episodes of reduced consciousness and seizures.
Hypomandibular faciocranial dysostosis (ORPHA:1790)
Hypomandibular faciocranial dysostosis is a cranial malformation characterized by facial dysmorphism (proptosis, frontal bossing, midface and zygomatic arches hypoplasia, short nose with anteverted nostrils, microstomia with persistent buccopharyngeal membrane, severe hypoglossia with glossoptosis, severe mandibular hypoplasia, and low set ears) associated with laryngeal hypoplasia and craniosynostosis. Other variable features include cleft palate, optic nerve coloboma and choanal stenosis.
Hypomyelination neuropathy-arthrogryposis syndrome (ORPHA:2680)
Hypomyelination neuropathy-arthrogryposis syndrome is a rare, genetic, limb malformation syndrome characterized by multiple congenital distal joint contractures (incl. talipes equinovarus and both proximal and distal interphalangeal joint contractures of the hands) and very severe motor paralysis at birth (i.e. lack of swallowing, autonomous respiratory function and deep tendon reflexes), leading to death within first 3 months of life. Fetal hypo- or akinesia, late-onset polyhydramnios and dramatically reduced, or absent, motor nerve conduction velocities (<10 m/s) are frequently associated. Nerve ultrastructural morphology shows severe abnormalities of the nodes of Ranvier and myelinated axons.
Hypomyelination of early myelinating structures (ORPHA:599376)
A rare genetic neurological disorder characterized by hypomyelination of early myelinating structures such as the brainstem, cerebellar white matter, optic radiation, and periventricular white matter, while structures acquiring myelin later are better myelinated. Patients present in infancy with nystagmus, developmental delay, and progressive ataxic-spastic or ataxic syndrome. Cognitive functions are normal or only mildly impaired.
Hypomyelination with atrophy of basal ganglia and cerebellum (ORPHA:139441)
A rare disorder characterized by slowly progressive spasticity, extrapyramidal movement disorders (dystonia, choreoathetosis and rigidity), cerebellar ataxia, moderate to severe cognitive deficit, and anarthria/dysarthria.
Epidemiology
So far, around 20 cases have been reported in the literature. The syndrome affects both males and females and onset occurs in infancy or early childhood.
Etiology
The etiology is unknown.
Diagnostic methods
H-ABC is diagnosed on the basis of the distinctive MRI findings of diffuse but partial hypomyelination of the cerebral hemispheres, mild to severe cerebellar atrophy and atrophy of the basal ganglia.
Genetic counseling
All of the reported cases were sporadic and the mode of inheritance remains unclear.

                            Last update: 
                            September 2008
Hypomyelination with brain stem and spinal cord involvement and leg spasticity (ORPHA:363412)
A rare genetic leukodystrophy characterized by diffuse hypomyelination in the supratentorial brain white matter, brain stem and spinal cord. Patients usually present nystagmus, lower limb spasticity, hypotonia, and motor developmental delay, as well as MRI signal abnormalities involving the corpus callosum, anterior brainstem, pyramidal tracts, superior and inferior cerebellar peduncles, dorsal columns and/or lateral corticospinal tracts.
Hypomyelination-congenital cataract syndrome (ORPHA:85163)
A rare developmental defect during embryogenesis characterized by congenital or early onset cataracts (usually bilateral), developmental delay, progressive neurologic symptoms (including ataxia, spasticity and sometimes seizures) and mild-to-moderate cognitive impairment. Other major clinical features include truncal hypotonia, dysarthia, cerebellar signs (e.g: truncal titubation and intention tremor) and peripheral neuropathy (e.g: progressive weakness of the muscles in the lower limbs). Hypomyelination associated with periventricular white matter abnormalities is observed. Some patients may have mild lens opacity and cataracts could be absent.
Hypophosphatemic rickets (ORPHA:437)
A group of genetic, renal phosphate wasting disorders characterized by hypophosphatemia, rickets, and normal serum levels of calcium. Characteristic clinical features include slow growth/short stature, bone pain and bone deformities.
Hypopigmentation-punctate palmoplantar keratoderma syndrome (ORPHA:324561)
A rare, genetic, epidermal disease characterized by punctate keratoderma on palms and soles associated with irregularly shaped hypopigmented macules (typically localized on the extremities). Ectopic calcification (e.g. early-onset calcific tendinopathy, calcinosis cutis) and pachyonychia may be occasionally associated.
Hypoplasia of the mitral valve annulus (ORPHA:99058)
A rare, congenital, mitral valve malformation characterized by hypoplastic annulus which usually appears within a complete mitral valve hypoplasia, causing mitral valve stenosis. Association with other cardiac malformation is common, including coarctation of the aorta, aortic valve stenosis, Shone complex and hypoplastic left heart syndrome.
Hypoplastic pancreas-intestinal atresia-hypoplastic gallbladder syndrome (ORPHA:293864)
A rare, potentially fatal, genetic, visceral malformation syndrome characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, as well as gallbladder aplasia or hypoplasia. Patients typically present intrauterine growth restriction, failure to thrive, malnutrition, intestinal malrotation, malabsorption, conjugated hyperbilirubinemia, acholia and infections. Cardiac anomalies may also be associated.
Hypoplastic right heart syndrome (ORPHA:98723)
A rare, cyanotic congenital heart malformation caused by underdevelopment of the right-sided heart structures (tricuspid valve, RV, pulmonary valve, and pulmonary artery) commonly associated with an atrial septal defect, ostium secundum type. Pulmonary blood flow is diminished and right-to-left shunting occurs at the atrial level, leading to dyspnea, fatigue, atrial arrhythmias, right-sided heart failure, hypoxemia, repeated miscarriages that were mostly due to hypoxemia and cyanosis. Two subtypes of HRHS have been characterized: pulmonary atresia-intact ventricular septum and right ventricular hypoplasia.
Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome (ORPHA:2250)
This syndrome is characterized by the association of severe nasal hypoplasia, hypoplasia of the eyes, hyposmia, hypogeusia and hypogonadotropic hypogonadism.
Epidemiology
It has been described in two males.
Clinical description
Additional features included bilateral inguinal hernias, undescended testes, and impaired vision with cataracts and colobomata.

                            Last update: 
                            May 2009
Hypospadias-intellectual disability, Goldblatt type syndrome (ORPHA:2261)
A very rare multiple congenital anomalies syndrome described in three brothers of one South-African family, and characterized by hypospadias and intellectual deficit, in association with microcephaly, craniofacial dysmorphism, joint laxity and beaked nails.
Hypothalamic adipsic hypernatraemia syndrome (ORPHA:443101)
A rare endocrine disease characterized by severe chronic hypernatremic dehydration caused by decreased intake of water based on impaired thirst perception, due to a selective defect in hypothalamic osmoregulation of thirst. Structural hypothalamic lesions are absent and arginine vasopressin secretion is normal.
Hypothalamic hamartomas with gelastic seizures (ORPHA:86906)
Hypothalamic hamartomas with gelastic seizures is a rare cerebral malformation with epilepsy syndrome characterized by early-onset gelastic (i.e. ictal laughter) or dacrystic (i.e., ictal crying) seizures due to non-neoplastic developmental malformation - hypothalamic hamartomas. In many patients, seizures progress to other seizure types including focal and generalized seizures, with concomitant cognitive decline and behavioral disorders. Some patients also present a precocious puberty.
Hypothyroidism due to deficient transcription factors involved in pituitary development or function (ORPHA:226307)
Hypothyroidism due to mutations in transcription factors involved in pituitary development or function is a type of central congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth, characterized by low levels of thyroid hormones caused by disorders in the development or function of the pituitary.
Epidemiology
Prevalence is unknown.
Clinical description
The clinical manifestations can be subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs often do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Goiter is always absent. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment hypothyroidism results in severe intellectual deficit and short stature. Clinical manifestations may often include signs of hypopituitarism including septo-optic dysplasia or cleft lip and/or palate among others.
Etiology
The hypothyroidism is caused by mutations in genes regulating pituitary gland development including HESX1, LHX3, LHX4, POU1F1 and PROP1 (3p21.2-p21.1, 9q34.3, 1q25, 3p11 and 5q) .

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Dr Stephen LAFRANCHI  - Dr Maynika RASTOGI
Hypothyroidism due to TSH receptor mutations (ORPHA:90673)
A type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth due to thyroid resistance to TSH.
Epidemiology
Resistance to TSH occurs in about 5% of cases of permanent congenital hypothyroidism.
Clinical description
Clinical manifestations are those of other forms of congenital hypothyroidism (CH; see this term). Goiter is always absent.
Etiology
Mutations in the TSH receptor gene (TSHR; 14q31) result in resistance to TSH, which causes a reduction in thyroid hormone production. Mutations in TSHR may also cause thyroid hypoplasia (see this term).

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Dr Stephen LAFRANCHI  - Dr Maynika RASTOGI
Hypotonia with lactic acidemia and hyperammonemia (ORPHA:137908)
This syndrome is characterised by severe hypotonia, lactic academia and congenital hyperammonaemia.
Epidemiology
It has been described in three newborns born to consanguineous parents.
Clinical description
Ultrasound examination during the 36th week of pregnancy revealed generalised oedema. Hypertrophic cardiomyopathy and tubulopathy developed within the first week of life and the infants died within the first month. The activities of enzymes in the mitochondrial respiratory chain were reduced in the muscles of the patients.
Etiology
Mutations were identified in the MRPS22 gene, encoding a mitochondrial ribosomal protein.

                            Last update: 
                            April 2008
Hypotonia-cystinuria syndrome (ORPHA:163690)
A rare, genetic disorder of amino acid absorption and transport, characterized by generalized hypotonia at birth, neonatal/infantile failure to thrive (followed by hyperphagia and rapid weight gain in late childhood), cystinuria type 1, nephrolithiasis, growth retardation due to growth hormone deficiency, and minor facial dysmorphism. Dysmorphic features mainly include dolichocephaly and ptosis. Nephrolithiasis occurs at variable ages.
Hypotonia-failure to thrive-microcephaly syndrome (ORPHA:79507)
Leukotriene C4 synthase deficiency is an extremely rare fatal neurometabolic developmental disorder characterized clinically by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly.
Hypotonia-speech impairment-severe cognitive delay syndrome (ORPHA:371364)
Hypotonia-speech impairment-severe cognitive delay syndrome is a rare, genetic neurodegenerative disorder characterized by severe, persistent hypotonia (presenting at birth or in early infancy), severe global developmental delay (with poor or absent speech, difficulty or inability to roll, sit or walk), profound intellectual disability, and failure to thrive. Additional manifestations include microcephaly, progressive peripheral spasticity, bilateral strabismus and nystagmus, constipation, and variable dysmorphic facial features (including plagiocephaly, broad forehead, small nose, low-set ears, micrognathia and open mouth with tented upper lip).
Hypotrichosis simplex of the scalp (ORPHA:90368)
Hypotrichosis simplex of the scalp (HSS) is characterized by diffuse progressive hair loss that is confined to the scalp.
Epidemiology
Prevalence is unknown but HSS has been described in multiple members (males and females) of several large families.
Clinical description
Progressive hair loss generally begins during the first decade of life and most patients are completely bald by the third decade of life. In contrast to the generalized form of hypotrichosis simplex (see this term), body, axillary and facial hair, as well as the eyebrows and eye lashes are unaffected in HSS. There are no anomalies of the skin, nails and teeth.
Etiology
The causative gene CDSN (encoding the keratinocyte adhesion molecule, corneodesmosin) has been mapped to chromosome 6p21.3.
Genetic counseling
HSS is transmitted in an autosomal dominant manner.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Pr Regina BETZ
Hypotrichosis simplex (ORPHA:55654)
Hypotrichosis simplex (HS) or hereditary hypotrichosis simplex (HHS) is characterized by reduced pilosity over the scalp and body (with sparse, thin, and short hair) in the absence of other anomalies.
Epidemiology
Prevalence is unknown but numerous large pedigrees with several affected members have been described. Both men and women are equally affected.
Clinical description
Hair loss is diffuse and progressive and usually begins during early childhood. Body hair may also be sparse with variable involvement of the eyebrows, eyelashes, and pubic and axillary hair. There are no anomalies of the skin, nails or teeth. A scalp-limited form, hypotrichosis simplex of the scalp (see this term) has also been reported with mutations in the corneodesmosin (CDSN) gene.
Etiology
Both autosomal dominant and recessive modes of transmission have been reported for HHS.Autosomal dominant HHS affecting both scalp and body hair has been reported in one Italian and two Pakistani families as due to mutations in the APCDD1 gene mapped to 18p11.22. Three clinically similar forms of localized autosomal recessive hypotrichosis (LAH1, LAH2 and LAH3) have been identified within the last years. The locus for LAH1 (involving mainly the hair of the scalp, chest, arms and legs) has been mapped to 18q12.1 and mutations in the desmoglein-4 (DSG4) gene have been identified. The locus for LAH2 (characterized by sparse or absent scalp, axillary and body hair, and sparse eyebrows and eyelashes) has been mapped to 3q27.3 and mutations in the lipase-H (LIPH) gene have been identified. The locus for LAH3 (characterized by progressive loss of scalp hair, sparse body hair, and normal eyebrows, eyelashes, and pubic and axillary hair) has been mapped to 13q14.11-q21.32 and mutations have been identified in a G protein-coupled receptor gene (P2RY5). These receptors belong to the group of lipophosphatidic acid (LPA) receptors and are therefore designated as LPAR6.
Management and treatment
There is no treatment for hypotrichosis simplex available to date.

                            Last update: 
                            June 2010


                            - Expert reviewer(s): 
                            Pr Regina BETZ
Hypotrichosis with juvenile macular degeneration (ORPHA:1573)
Hypotrichosis with juvenile macular degeneration (HJMD) is a very rare syndrome characterized by sparse and short hair from birth followed by progressive macular degeneration leading to blindness.
Epidemiology
Prevalence is unknown but approximately 50 patients have been described since the first characterization of the syndrome in 1935.
Clinical description
HJMD patients present with short and sparse scalp hair since birth or first months of life, with no subsequent growth during life. A decade later, during the first to third decades of life, visual acuity decreases because of progressive macular degeneration, leading in many cases to blindness between the second and fourth decades of life. HJMD is sometimes associated with limb anomalies, in which case it is termed Ectodermal dysplasia, Ectrodactyly, and Macular dystrophy (EEM; see this term). Many patients display fair hair complexion as compared with their healthy siblings. The hair phenotype does not improve significantly with age, even though diffuse alopecia in infancy can evolve towards short and sparse hair in puberty.
Etiology
HJMD is caused by mutations in the CDH3 gene (16q22.1), encoding P-cadherin. P-cadherin is part of adherens junctions in various epithelia including the hair follicular epithelium. Moreover, P-cadherin is expressed in the retinal pigment epithelium.
Diagnostic methods
Diagnosis is based on the combined occurrence of hypotrichosis with characteristic degenerative changes and pigmentary abnormalities of the macula on fundoscopy. Where available, electrophysiologic studies can confirm abnormal function of the posterior pole. Additional tests of lesser diagnostic value include (1) histopathologic examination of scalp biopsies, revealing mostly vellus and catagen hair follicles with significantly reduced number of terminal hair follicles; (2) light microscopy and scanning electron microscopy of hair which can demonstrate various structural abnormalities including pseudomonilethrix, pili torti, longitudinal ridging, scaling and folding of the hair shaft.
Differential diagnosis
Differential diagnosis includes EEM syndrome, also caused by CDH3 mutations.
Antenatal diagnosis
DNA-based prenatal diagnosis and genetic counseling are available provided the underlying mutation is known.
Genetic counseling
As HJMD is an autosomal recessive disease, risk of recurrence is 25%.
Management and treatment
No curative or palliative options exist for HJMD. However, educational measures can be implemented and psychological support should be provided once HJMD is diagnosed.
Prognosis
The most severe complication of HJMD is progressive macular degeneration leading to blindness between the second and fourth decades of life. Life expectancy is normal but quality of life can be reduced because of blindness and psychological impact due to the hair phenotype.

                            Last update: 
                            August 2011


                            - Expert reviewer(s): 
                            Dr Liat SAMUELOV  - Pr Eli SPRECHER