TaoMedAI/RareMedData huggingface dataset:
Hyperinsulinism due to UCP2 deficiency (ORPHA:276556)
A rare form of congenital diazoxide-sensitive diffuse hyperinsulinism due to UCP2 deficiency and characterized by hypoglycemic episodes from the neonatal period, a good clinical response to diazoxide and a probable transient nature of the disease with spontaneous resolution.
Hyperinsulinism-hyperammonemia syndrome (ORPHA:35878)
A rare diffuse form of congenital hyperinsulinism characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia), chronic hyperammonemia and recurrent episodes of hypoglycemia induced by fasting and protein rich meals. Epilepsy and cognitive deficit, which are unrelated to hypoglycemia but possibly related to the chronic hyperammonemia, may also occur. This disorder is usually responsive to diazoxide treatment.
Hyperkeratosis lenticularis perstans (ORPHA:409)
A rare skin disease characterized by usually asymptomatic, hyperkeratotic, reddish-brown papules primarily located on the lower extremities. Histological examination shows lamellar hyperkeratosis with abrupt peripheral basket-weave orthokeratosis, irregular acanthosis, and underlying lichenoid lymphocytic infiltrate. The condition may be sporadic or familial.
Hyperkeratosis-hyperpigmentation syndrome (ORPHA:1336)
Hyperkeratosis-hyperpigmentation syndrome describes a very rare hyperpigmentation of the skin characterized by tiny hyperpigmented spots mainly on skin exposed to sunlight, together with mild punctate palmoplantar papular hyperkeratosis as a major feature. There have been no further descriptions in the literature since 1993.
Hyperlipidemia due to hepatic triacylglycerol lipase deficiency (ORPHA:140905)
A rare hyperalphalipoproteinemia characterized by elevated plasma cholesterol and triglyceride (TG) levels with a marked TG enrichment of low- and high-density lipoproteins (HDL), presence of circulating beta-very low density lipoproteins and elevated HDL cholesterol levels, in the presence of a very low, or undetectable, postheparin plasma hepatic lipase activity. Premature atherosclerosis and/or coronary heart disease may be associated.
Hyperlysinemia (ORPHA:2203)
A rare autosomal recessive disorder of lysine metabolism characterized by elevated levels of lysine in the cerebrospinal fluid and blood. Hyperlysinemia type I has been associated with a highly variable phenotype including seizures, hypotonia, and mild psychomotor delay, although isolated hyperlysinemia is probably a benign condition.
Hypermethioninemia due to glycine N-methyltransferase deficiency (ORPHA:289891)
Hypermethioninemia due to glycine N-methyltransferase deficiency is a rare, genetic inborn error of metabolism characterized by a relatively benign clinical phenotype, with only mild to moderate hepatomegaly reported, in addition to laboratory studies revealing permanent, greatly increased hypermethioninemia, mild to moderate elevation of aminotransferases and highly elevated plasma S-adenosyl-methionine with normal S-adenosylhomocysteine and total homocysteine.
Hypermethioninemia encephalopathy due to adenosine kinase deficiency (ORPHA:289290)
Hypermethioninemia encephalopathy due to adenosine kinase deficiency is a rare inborn error of metabolism disorder characterized by persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine which manifests with encephalopathy, severe global developmental delay, mild to severe liver dysfunction, hypotonia and facial dysmorphism (most significant is frontal bossing, macrocephaly, hypertelorism and depressed nasal bridge). Epileptic seizures, hypoglycemia and/or cardiac defects (pulmonary stenosis, atrial and/or ventricular septal defect, coarctation of the aorta) may be associated. Clinical picture may range from neurological symptoms only to multi-organ involvement.
Hyperostosis corticalis generalisata (ORPHA:3416)
Hyperostosis corticalis generalisata, also known as van Buchem disease, is a rare craniotubular hyperostosis characterized by hyperostosis of the skull, mandible, clavicles, ribs and diaphyses of the long bones, as well as the tubular bones of the hands and feet. Clinical manifestations include increased skull thickness with cranial nerve entrapment causing inconsistent cranial nerve palsies.
Hyperostosis cranialis interna (ORPHA:443098)
A rare primary bone dysplasia with increased bone density characterized by slowly progressive endosteal hyperostosis and osteosclerosis exclusively of the skull base and the calvaria, resulting in entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII. First symptoms often appear during the second decade of life and include disturbances in smell, vision, facial sensation and expression, hearing, and balance, as well as headaches due to increased ocular and intracranial pressure. After the fourth decade, radiological progression is minimal, although decreased intracranial volume can lead to death in severe cases.
Hyperparathyroidism-jaw tumor syndrome (ORPHA:99880)
A rare genetic disease characterized by synchronous or metachronous occurrence of primary hyperparathyroidism and ossifying fibroma of the maxilla and/or mandible, associated with an increased risk of parathyroid carcinoma. Occurrence of renal cysts or tumors, multiple uterine polyps, and thyroid tumors has also been reported.
Hyperphenylalaninemia due to DNAJC12 deficiency (ORPHA:508523)
A rare inborn error of metabolism characterized by increased serum phenylalanine, associated with variable neurological symptoms ranging from mild autistic features or hyperactivity to severe intellectual disability, dystonia, and parkinsonism. Laboratory analyses show normal tetrahydrobiopterin (BH4) metabolism and low levels of the CSF monoamine neurotransmitter metabolites homovanillic acid and 5-hydroxyindoleacetic acid.
Hyperphosphatasia-intellectual disability syndrome (ORPHA:247262)
A rare, congenital disorder of glycosylation-related bone disorder characterized by hypotonia, severe developmental delay, intellectual disability, seizures, increased serum alkaline phosphatase, short distal phalanges with hypoplastic nails, and dysmorphic facial features. In some cases, cleft palate, megacolon, anorectal malformations, and congenital heart defects have been reported.
Hyperprolinemia type 1 (ORPHA:419)
A rare disorder of proline metabolism characterized biochemically by markedly elevated levels of proline in plasma and urine due to deficiency of proline oxidase. The reported clinical phenotype ranges from asymptomatic to variable neurologic and psychiatric manifestations (including global developmental delay, seizures, autistic features, and hyperactivity).
Hyperprolinemia type 2 (ORPHA:79101)
Hyperprolinemia type 2 is an autosomal recessive proline metabolism disorder due to pyroline-5-carboxylate dehydrogenase deficiency. The condition is often benign but clinical signs may include seizures, intellectual deficit and mild developmental delay.
Hypertelorism-hypospadias-polysyndactyly syndrome (ORPHA:2211)
Hypertelorism-hypospadias-polysyndactyly syndrome is a very rare syndrome associating an acro-fronto-facio-nasal dysostosis with genitourinary anomalies.
Epidemiology
It has been described in three families.
Clinical description
Craniofacial manifestations include wide anterior fontanel, flat occiput, hypertelorism, ptosis, proptosis, broad nasal bridge and nasal tip, long philtrum and posteriorly rotated or low set ears. Hypospadias and shawl scrotum are present in all males. Acral manifestations include syndactyly of fingers, broad thumbs or halluces or preaxial polydactyly. The affected patients have no intellectual deficit.
Genetic counseling
The condition seems to be hereditary, and transmitted as an autosomal recessive trait.

                            Last update: 
                            October 2010
Hypertelorism-microtia-facial clefting syndrome (ORPHA:2213)
Hypertelorism-microtia-facial clefting syndrome, or HMC syndrome, is a very rare syndrome characterized by the combination of hypertelorism, cleft lip and palate and microtia.
Epidemiology
Nine cases have been reported in the literature in seven families.
Clinical description
Some patients have associated cardiac or renal congenital malformations. Short stature and intellectual deficiency are common.
Antenatal diagnosis
Antenatal diagnosis is possible by ultrasonographic monitoring.
Genetic counseling
The reported cases support autosomal recessive inheritance.

                            Last update: 
                            March 2010
Hypertelorism-preauricular sinus-punctual pits-deafness syndrome (ORPHA:293958)
A rare developmental defect during embryogenesis syndrome characterized by hypertelorism, bilateral preauricular sinus, bilateral punctal pits, lacrimal duct obstruction, hearing loss, abnormal palmar flexion creases and bilateral distal axial triradii. Shawl scrotum has also been reported.
Hypertension due to gain-of-function mutations in the mineralocorticoid receptor (ORPHA:88660)
A rare genetic cause of hypertension characterized by severe early-onset therapy-resistant hypertension due to a gain-of-function mutation in the mineralocorticoid receptor. The condition is associated with suppressed plasma renin activity and low serum aldosterone levels and is markedly exacerbated during pregnancy.
Hypertrichosis cubiti (ORPHA:2220)
Hypertrichosis cubiti is a rare hair anomaly characterized by symmetrical, congenital or early-onset, bilateral hypertrychosis localized on the externsor surfaces of the upper extremities (especially the elbows). Short stature, or other abnormalities, such as developmental delay, facial anomalies and intellectual disability, may or may not be associated.
Hypertrichosis lanuginosa congenita (ORPHA:2222)
Hypertrichosis lanuginosa congenita is a rare congenital skin disease characterized by the presence of 3 to 5cm long lanugo-type hair on the entire body, with the exception of palms, soles, and mucous membranes.
Hypertrophic cardiomyopathy with kidney anomalies due to mitochondrial DNA mutation (ORPHA:324525)
A mitochondrial oxidative phosphorylation disorder characterized by hypertrophic and dilated cardiomyopathy, failure to thrive, myopathy with generalized hypotonia and increased creatine kinase, developmental delay and/or regression with cerebral atrophy on brain MRI, renal manifestations including chronic renal failure, renal tubular acidosis and lactic acidosis. Additional clinical features include seizures and respiratory failure.
Hypertrophic or verrucous lupus erythematosus (ORPHA:90282)
Hypertrophic or verrucous lupus erythematosus is a rare type of chronic cutaneous lupus erythematosus characterized by the appearance of lesions on sun-exposed areas (frequently the extensor surfaces of forearms, face, upper trunk) which vary from squamous violet, painful papules and blackish hyperkeratotic ulcers to depigmented atrophic plaques on the back, hyperkeratotic papules on upper extremities, and disseminated keratoacanthoma-like papulonodular verrucous lesions. Classic discoid lesions and squamous cell carcinoma may be associated. Histopathology reveals follicular plugging, liquefactive basal layer degeneration and a perivascular lymphocytic infiltrate.
Hypertryptophanemia (ORPHA:2224)
A rare inborn error of metabolism characterized by congenital hypertryptophanemia and hyperserotonemia. Patients are typically asymptomatic, although developmental delay, intellectual disability, and behavioral abnormalities, among others, have been reported in association.
Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (ORPHA:363694)
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.
Hyperzincemia and hypercalprotectinemia (ORPHA:251523)
A rare inborn error of zinc metabolism characterized by recurrent infections, hepatosplenomegaly, anemia (unresponsive to iron supplementation) and chronic systemic inflammation in the presence of high plasma concentrations of zinc and calprotectin. Patients typically present dermal ulcers or other cutaneous manifestations (e.g. inflammation) and arthralgia. Severe epistaxis and spontaneous hematomas have also been reported.
Hypnic headache (ORPHA:276429)
A rare headache characterized by recurrent brief, intense headache attacks occurring exclusively during sleep, typically at the same time of the night, causing the patient to wake up. The pain usually lasts more than 15 minutes after waking. It is mostly bilateral and may be associated with nausea, photophobia, or phonophobia, while characteristically no autonomic symptoms are present.
Hypo- and hypermelanotic cutaneous macules-retarded growth-intellectual disability syndrome (ORPHA:2435)
Hypo- and hypermelanotic cutaneous macules-retarded growth-intellectual disability syndrome is a rare, genetic pigmentation anomaly of the skin disorder characterized by congenital hypomelanotic and hypermelanotic cutaneous macules associated with, in some patients, retarded growth and intellectual disability. There have been no further descriptions in the literature since 1978.
Hypocalcemic rickets (ORPHA:289103)
A group of rare genetic, vitamin D metabolism disorders characterized by hypocalcemia and rickets, and comprising of hypocalcemic vitamin D dependent rickets (VDDR-I) and hypocalcemic vitamin D resistant rickets (HVDRR). Characteristic clinical features include slow growth, bone pain and bone deformities. HVDRR is associated with resistance to vitamin D treatment.
Hypocalcemic vitamin D-resistant rickets (ORPHA:93160)
A rare genetic, disorder of vitamin D metabolism characterized by hypocalcemia, severe rickets and in many cases alopecia.
Epidemiology
The prevalence is unknown.
Clinical description
Progressive rickets manifest during the first years of life with poor growth and skeletal deformities. Total body alopecia is present in severe forms of the disease (2/3 of cases). In some cases, skin lesions or epidermal cysts can be observed along with alopecia. The disease presents a broad clinical picture that largely depends on the genotype.
Etiology
The disease is due to mutations in the vitamin D receptor gene (VDR; 12q13-14) that decrease the receptor's action thereby preventing calcitriol's action. This leads to an impaired intestinal absorption of calcium and phosphate.
Diagnostic methods
Diagnosis is based on clinical, biochemical and radiological findings. Biochemical features are severe hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, normal serum levels of calcidiol (25-hydroxyvitamin D), elevated serum levels of calcitriol (1,25-dihydroxyvitamin D3, the active form of vitamin D), and high serum levels of alkaline phosphatase. Radiological findings include typical rickets and/or osteomalacia and decreased bone mineralization. Osteitis fibrosa cystica due to secondary hyperparathyroidism is commonly observed.
Differential diagnosis
Differential diagnosis includes other forms of rickets (hereditary and nutritional) and atrichia with papular lesions (APL) and hypocalcemic vitamin D-dependent rickets.
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
Treatment aims at improving growth, correcting hypocalcemia and hyperparathyroidism, and at enhancing mineralization of bones. In patients with mild forms it consists of daily administration of high doses of calcitriol and calcium; intravenous administration may be needed in severe phenotypes. Response to treatment largely depends on the severity of the disease. Patients with alopecia generally do not respond to oral treatment and need intravenous calcium infusions. Regular monitoring of biochemical parameters is required.
Prognosis
Correction of rachitic deformities depends on the severity of the disease.

                            Last update: 
                            August 2022


                            - Expert reviewer(s): 
                            Pr Agnès LINGLART | Endo-ERN* - Dr Anya ROTHENBUHLER | Endo-ERN*


                                * European Reference Network
Hypochondroplasia (ORPHA:429)
A primary bone dysplasia with micromelia characterized by disproportionate short stature, mild lumbar lordosis and limited extension of the elbow joints.
Epidemiology
Hypochondroplasia estimated incidence is 1/50,000. The exact prevalence is unknown.
Clinical description
Hypochondroplasia is a skeletal dysplasia characterized by short stature; stocky build; disproportionately short arms and legs; broad, short hands and feet; mild joint laxity; and macrocephaly. Radiologic features include shortening of long bones with mild metaphyseal flare; narrowing of the inferior lumbar interpedicular distances; short, broad femoral neck; and squared, shortened ilia. The skeletal features are very similar to those seen in achondroplasia but tend to be milder. Medical complications common to achondroplasia (e.g., spinal stenosis, tibial bowing, obstructive apnea) occur less frequently in hypochondroplasia. Children usually present as toddlers or school-age children with decreased growth velocity leading to short stature and limb disproportion. However, some more severe cases are detected prenatally, at birth or in early infancy. Other features also become more prominent over time.
Etiology
The disorder is caused by mutations in the fibroblast growth factor receptor-3 gene (FGFR3; 4p16.3).
Diagnostic methods
Hypochondroplasia is diagnosed by the recognition of characteristic clinical and radiologic findings that remain controversial. DNA-based testing is possible and about 70% of affected individuals are heterozygous for a pathogenic variant in FGFR3. The most frequent variant is NM_000142.4:c.1620C>A; p.Asn540Lys (p.N540K), which accounts for approximately 60% of affected individuals.
Differential diagnosis
Hypochondroplasia closely resembles achondroplasia (also caused by variants in the FGFR3 gene). Differential diagnosis also includes mild forms of mesomelic dwarfism, mild forms of spondyloepiphyseal-metaphyseal dysplasias, Leri-Weill dyschondrosteosis, Pseudohypoparathyroidism and pseudopseudohypoparathyroidism.
Genetic counseling
The disorder is transmitted in an autosomal dominant manner. Genetic counseling should be proposed to individuals having the disease-causing variant informing them that there is 50% risk of passing the variant to offspring.
Management and treatment
Management of short stature in hypochondroplasia is influenced by parental expectations and concerns; one approach is to address these concerns rather than trying to treat the child. Laminectomy relieves symptoms of spinal stenosis; about 70% of individuals experience relief of symptoms following decompression without laminectomy. Developmental milestones are followed closely during early childhood so that cognitive impairments are addressed with special educational programs. Epilepsy is treated in the standard fashion.
Prognosis
Final adult height varies between 132 and 147 cm and life expectancy is normal.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Dr Karen HEATH
Hypodontia-dysplasia of nails syndrome (ORPHA:2228)
Hypodontia-nail dysplasia syndrome is a form of ectodermal dysplasia.
Epidemiology
Its incidence has been estimated at around 1-2 in 10,000.
Clinical description
The primary teeth are usually normal but the permanent teeth often fail to erupt. The mandibular incisors, second molars, and maxillary canines are frequently absent and the crowns may be small and conical. Lip eversion may be present. Nails are usually small, thin and brittle with longitudinal ridges, pitting and koilonychias. Congenital absence of the nail plate has also been reported. Toenails are usually more severely affected than fingernails. Sweat glands, heat tolerance and hair are normal, although fine hair has been described in some cases.
Etiology
The syndrome is caused by a mutation in the MSX1 gene (4p16.1).
Diagnostic methods
Diagnosis is usually made during mid-childhood when persistence of the primary dentition becomes apparent, but the syndrome may be difficult to diagnose as the nail defects may be mild.
Differential diagnosis
The differential diagnosis should include other forms of ectodermal dysplasia, in particular hypohidrotic ectodermal dysplasia (see these terms).
Genetic counseling
Transmission is autosomal dominant.
Management and treatment
There is no specific treatment but oral health care and dental management are recommended.
Prognosis
The prognosis is good. The nail defects usually become less apparent with age and the nails often appear normal by adulthood.

                            Last update: 
                            March 2007


                            - Expert reviewer(s): 
                            Pr Alain VERLOES
Hypoglossia-hypodactyly syndrome (ORPHA:989)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by hypoglossia, micrognathia and variable limb abnormalities. Limb defects can involve any limb (usually all four) and the severity may vary from the absence of distal phalanges to total absence of digits or limbs. Synbrachydactyly may also be present. Patients have problems with speech, swallowing and mastication, and they have additional craniofacial anomalies (including telecanthus, lower eyelid defects, broad nose, microstomia, variable clefting or aberrant attachments of tongue, mandibular hypodontia, cleft palate, cranial nerve palsies, and facial asymmetry). Gingival abnormalities are frequently observed. Intelligence and stature are generally normal.
Hypogonadism-mitral valve prolapse-intellectual disability syndrome (ORPHA:2233)
This syndrome is characterized by the association of hypogonadism due to primary gonadal failure, mitral valve prolapse, mild intellectual deficit and short stature.
Epidemiology
It has been described in two brothers.
Clinical description
Growth hormone (GH) levels and the response to gonadotropin stimulation tests were also abnormal.

                            Last update: 
                            May 2009
Hypogonadotropic hypogonadism-frontoparietal alopecia syndrome (ORPHA:2230)
This syndrome is characterized by the association of hypogonadotropic hypogonadism and frontoparietal alopecia.
Epidemiology
It has been described in six members (four males and two females) of a consanguineous Lebanese family.
Clinical description
In addition to frontoparietal alopecia, the remaining scalp hair was also sparse, and axillary and pubic hair was absent.
Etiology
In contrast to the syndrome of primary hypergonadotropic hypogonadism and partial alopecia (see this term), streak or absent ovaries, hypoplastic uterus, and microcephaly were not reported in the affected female members of this Lebanese family.
Genetic counseling
Despite the family history of consanguinity, autosomal dominant inheritance with reduced penetrance was considered as the most likely mode of transmission.

                            Last update: 
                            May 2009
Hypogonadotropic hypogonadism-retinitis pigmentosa syndrome (ORPHA:2235)
A rare endocrine syndrome characterized by the association of hypogonadotropic hypogonadism (with primary amenorrhea and lack of secondary sexual development) and retinitis pigmentosa.