TaoMedAI/RareMedData huggingface dataset:
Inherited epidermolysis bullosa (ORPHA:79361)
Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues.
Epidemiology
All types and subtypes of EB are rare; the overall incidence and prevalence of the disease in the United States are approximately 1/53,000 live births and 1/125,000, respectively, and similar estimates have been obtained in some European countries. EB affects individuals from all ethnic origins and there is no gender predilection.
Clinical description
Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Four major types of inherited EB have been defined: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), each with numerous subtypes, and Kindler syndrome (see these terms). These forms differ not only phenotypically and genotypically but more importantly by the site of ultrastructural disruption or cleavage.
Etiology
Each EB subtype is known to arise from mutations within the genes coding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis.
Diagnostic methods
EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis.
Differential diagnosis
Extensive differential diagnosis is not usually required in EB.
Antenatal diagnosis
Molecular prenatal diagnosis may be available if the disease-causing mutation in the family has been identified.
Genetic counseling
EB is inherited in either an autosomal dominant or autosomal recessive manner, depending on the EB type and subtype. Genetic counseling should be offered to affected families.
Management and treatment
Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct the extracutaneous complications, whenever possible.
Prognosis
Prognosis varies considerably and is based on both EB subtype and the overall health of the patient.

                            Last update: 
                            June 2011


                            - Expert reviewer(s): 
                            Pr Jo-David FINE
Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency (ORPHA:289548)
Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency is a rare, genetic, chronic, primary adrenal insufficiency disorder, due to partial loss-of-function CYP11A1 mutations, characterized by early-onset adrenal insufficiency without associated abnormal external male genitalia. Patients present with signs of adrenal crisis, including electrolite abnormalities, severe weakness, recurrent vomiting and seizures. Ultrasound reveals absent (or very small) adrenal glands.
Inherited isolated arrhythmogenic cardiomyopathy (ORPHA:217656)
Familial isolated arrhythmogenic right ventricular dysplasia (ARVC) is the familial autosomal dominant form of ARVC (see this term), a heart muscle disease characterized by life-threatening ventricular arrhythmias with left bundle branch block configuration that may manifest with palpitations, ventricular tachycardia, syncope and sudden fatal attacks, and that is due to dystrophy and fibro-fatty replacement of the right ventricular myocardium that may lead to right ventricular aneurysms.
Iniencephaly (ORPHA:63259)
Iniencephaly is a rare form of neural tube defect in which a malformation of the cervico-occipital junction is associated with a malformation of the central nervous system.
Epidemiology
Incidence is estimated at between 1/1,000 and 1/100,000 live births, depending on the geographical area, and more female infants are affected (male:female sex ratio: 1:3 to 1:9).
Clinical description
The cardinal features are occipital bone defect, partial or total absence of cervicothoracic vertebrae, fetal retroflexion of the head and characteristic absence of the neck. It is associated with malformations of the central nervous (spina bifida and/or anencephaly), gastrointestinal (omphalocele) and cardiovascular systems.
Etiology
As with other neural tube defects, it is thought to be of multifactorial origin.
Antenatal diagnosis
Antenatal diagnosis is possible by ultrasonographic monitoring.
Prognosis
Prognosis is poor and iniencephaly is almost always lethal.

                            Last update: 
                            January 2010
Insulin autoimmune syndrome (ORPHA:411593)
A rare endocrine disease characterized by hyperinsulinemic hypoglycemia associated with the presence of autoantibodies to endogenous insulin without previous exposure to exogenous insulin. Patients usually present in adulthood with postprandial, fasting-, or exercise-induced hypoglycemia, often with pronounced neuroglycopenic symptoms. Laboratory investigations reveal markedly elevated serum insulin, as well as increased C-peptide and proinsulin. The condition may be associated with other autoimmune diseases, monoclonal gammopathy, and/or recent exposure to certain medications.
Insulin-resistance syndrome type A (ORPHA:2297)
Type A insulin-resistance syndrome belongs to the group of extreme insulin-resistance syndromes (which includes leprechaunism, the lipodystrophies, Rabson-Mendenhall syndrome and type B insulin resistance syndrome; see these terms) and is characterized by the triad of hyperinsulinemia, acanthosis nigricans (skin lesions associated with insulin resistance), and signs of hyperandrogenism in females without lipodystrophy and who are not overweight.
Epidemiology
It is a rare disorder of unknown prevalence.
Clinical description
It is generally diagnosed in young women with marked signs of hyperandrogenism, but insulin resistance and acanthosis nigricans may be observed in men and in childhood. Acromegaloid facies or muscular cramps are sometimes associated. Hyperinsulinemia, a biological marker for insulin resistance, is often associated with glucose tolerance defects over the course of the disease, and diabetes progressively sets in. Hyperandrogenism (associated with polycystic ovarian syndrome (see this term) or ovarian hyperthecoses) leads to fertility problems.
Etiology
In some cases, the syndrome is caused by heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2), affecting the region encoding the tyrosine kinase domain. Cases associated with homozygous mutations affecting the insulin-binding domain of the receptor have also been reported. However, only 15 to 20% of female patients with hyperandrogenism, insulin resistance and acanthosis nigricans present mutations in the insulin receptor gene. When such mutations are not found, the disease is of unknown cause and may be considered as an HAIR-AN syndrome (see this term).
Differential diagnosis
The differential diagnosis includes the other forms of extreme insulin-resistance, in particular the lipodystrophy syndromes (see these terms), in which the reparation anomaly of the adipose tissue may be clinically minor. The differential diagnosis with type B insulin resistance syndrome is based on the lack of insulin anti-receptor auto-antibodies in patients with the type A syndrome.
Genetic counseling
Transmission is autosomal dominant.
Management and treatment
The treatment consists of dietary changes and/or drugs (metformin, glitazones, or other antidiabetic drugs) to reduce the insulin resistance and treat the diabetes.

                            Last update: 
                            January 2009


                            - Expert reviewer(s): 
                            Pr Corinne VIGOUROUX
Insulin-resistance syndrome type B (ORPHA:2298)
A rare genetic disease that belongs to the group of extreme insulin-resistance syndromes and is due to autoantibodies directed against insulin receptor.
Epidemiology
Insulin-resistance syndrome type B is a rare disorder that mainly affects middle-aged adults, predominantly females. The prevalence is unknown.
Clinical description
The disease may occur in the context of other autoimmune phenomena or well-characterized autoimmune diseases (mainly systemic lupus erythematosus). The onset of the disease is usually characterized by the appearance of a rapidly progressive, severely insulin-resistant diabetes with acanthosis nigricans (the typical skin lesion associated with insulin resistance), weight loss, and hirsutism in females. Hypoglycemia can occur during the course of the disease, or, more rarely, can be the only metabolic manifestation, and may be extremely severe. Unlike most insulin resistance syndromes, type B insulin resistance is not associated with hypertriglyceridemia.
Etiology
The syndrome is associated with the presence of serum auto-antibodies directed against the insulin receptor.
Diagnostic methods
The diagnosis is based on the clinical picture and results of laboratory tests. The detection of anti-insulin receptor auto-antibodies in the serum is rarely performed for routine diagnosis, so that the diagnosis is usually based on probabilistic arguments.
Differential diagnosis
The differential diagnosis include other insulin resistance syndromes and/or hypoglycemia due to other causes.
Management and treatment
Immunosuppressive combination therapies including rituximab were shown effective to induce remission in most cases and should be followed by maintenance immunosuppressive therapy. Non specific therapies should be associated to reverse the hypercatabolic state and treat hyperglycemia (large amount of insulin) and/or hypoglycemia (diet, adaptation of insulin therapy, steroids).
Prognosis
Prognosis depends on the course of the underlying autoimmune disease, and is unfavorable in cases with hypoglycemia (reported to lead to death in 50% of cases).

                            Last update: 
                            June 2021


                            - Expert reviewer(s): 
                            Pr Corinne VIGOUROUX
Intellectual disability, Birk-Barel type (ORPHA:166108)
Intellectual disability, Birk-Barel type is a rare, genetic, syndromic intellectual disability characterized by congenital central hypotonia, developmental delay, moderate to severe intellectual disability and subtle dysmorphic features which evolve over time (dolichocephaly, myopathic facies, ptosis, short and broad philtrum, tented upper lip vermillion, palatal anomalies, mild micro- and/or retrognathia). Patients present reduced facial movements, lethargy, weak cry, transient neonatal hypoglycemia, severe feeding difficulties and failure to thrive. Dysphagia, particularly of solid food, asthenic body build, joint contractures and scoliosis are additional features.
Intellectual disability, Buenos-Aires type (ORPHA:3079)
Intellectual disability, Buenos-Aires type is a rare intellectual disability syndrome characterized by growth retardation, microcephaly, characteristic facial features (including narrow forehead, bushy eyebrows, hypertelorism, small, downward-slanting palpebral fissures with blepharoptosis, malformed and low-set ears, broad straight nose, thin upper lip, and a wide, tented mouth), developmental delay, intellectual disability, speech disorder, and multiple organ malformations (e.g. ventricular septal defect, megaloureter, dilated renal pelvis). Additional manifestations reported include neurocutaneous lesions (including palmoplantar hyperkeratosis), internal hydrocephalus, and bilateral partial soft-tissue syndactyly of second and third toe.
Intellectual disability, Wolff type (ORPHA:3080)
Intellectual disability, Wolff type is a rare intellectual disability syndrome characterized by severe intellectual disability, characteristic facial features (low anterior hairline, upward slanting palpebral fissures, ocular hypertelorism, broad, bulbous nose, large ears with helix incompletely developed, thick lips, and micrognathia) and additional anomalies including peripheral joint contractures, delayed skeletal maturation, bilateral cleft lip and palate, strabismus, terminal hypoplasia of fingers, hypospadias, and bilateral inguinal hernias.
Intellectual disability-alacrima-achalasia syndrome (ORPHA:289483)
Intellectual disability-alacrima-achalasia syndrome is a rare, genetic intellectual disability syndrome characterized by delayed motor and cognitive development, absence or severe delay in speech development, intellectual disability, and alacrima. Achalasia/dysphagia and mild autonomic dysfunction (i.e. anisocoria) have also been reported in some patients. The phenotype is similar to the one observed in autosomal recessive Triple A syndrome, but differs by the presence of intellectual disability in all affected individuals.
Intellectual disability-autism-speech apraxia-craniofacial dysmorphism syndrome (ORPHA:529965)
A rare, syndromic intellectual disability characterized by developmental delay, speech apraxia, autism with stereotypies, intellectual disability and unspecific dysmorphic facial features. Seizures or isolated EEG abnormalities may also be associated.
Intellectual disability-balding-patella luxation-acromicria syndrome (ORPHA:3041)
Intellectual disability-balding-patella luxation-acromicria syndrome is characterised by severe intellectual deficit, patella luxations, acromicria, hypogonadism, facial dysmorphism (including midface hypoplasia and premature frontotemporal balding). It has been described in three unrelated males.
Intellectual disability-brachydactyly-Pierre Robin syndrome (ORPHA:364577)
Intellectual disability-brachydactyly-Pierre Robin syndrome is a rare developmental defect during embryogenesis syndrome characterized by mild to moderate intellectual disability and phsychomotor delay, Robin sequence (incl. severe micrognathia and soft palate cleft) and distinct dysmorphic facial features (e.g. synophris, short palpebral fissures, hypertelorism, small, low-set, and posteriorly angulated ears, bulbous nose, long/flat philtrum, and bow-shaped upper lip). Skeletal anomalies, such as brachydactyly, clinodactyly, small hands and feet, and oral manifestations (e.g. bifid, short tongue, oligodontia) are also associated. Additional features reported include microcephaly, capillary hemangiomas on face and scalp, ventricular septal defect, corneal clouding, nystagmus and profound sensorineural deafness.
Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome (ORPHA:508498)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by intrauterine and postnatal growth restriction, global developmental delay, intellectual disability, and dysmorphic facial features (such as broad nasal root, anteverted nares, long philtrum, low-set and posteriorly rotated ears, and short neck). Additional reported manifestations are microcephaly, short stature, vertebral abnormalities, joint laxity, ocular, cardiac, and renal defects, and minor limb anomalies. Brain imaging may show hypoplastic corpus callosum, delayed myelination, and cerebral atrophy.
Intellectual disability-cataracts-calcified pinnae-myopathy syndrome (ORPHA:3042)
Intellectual disability-cataracts-calcified pinnae-myopathy syndrome is a rare, genetic intellectual disability syndrome characterized by macrocephaly, hypotonia, dysmorphic facial features (wide forehead, ptosis, downslanting palpebral fissures, enlarged and calcified external ears, large jaw), sparse body hair, tall stature, and intellectual disability. Hearing loss, insulin-resistant diabetes, and progressive distal muscle wasting (leading to joint contractures) have also been reported in adulthood. Rare manifestations include behavioral abnormalities (aggression and restlessness), hypothyroidism, cerebral calcification, ataxia, and peripheral neuropathy.
Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome (ORPHA:397709)
A rare, genetic, central nervous system malformation syndrome characterized by early-onset, progressive, severe cerebellar ataxia associated with progressive, moderate to severe intellectual disability, global developmental delay, progressively coarsening facial features, relative macrocephaly and absence of seizures. Sensorineural hearing loss may be associated. Neuroimaging reveals cerebellar atrophy/hypoplasia.
Intellectual disability-developmental delay-contractures syndrome (ORPHA:3454)
Intellectual disability-developmental delay-contractures syndrome, formerly known as Wieacker-Wolff syndrome, is a severe X-linked recessive neurodevelopmental disorder characterized by severe contractures (arthrogryposis; see this term) and intellectual disability.
Epidemiology
Prevalence and incidence rates are not known. The syndrome has been reported in 5 families to date, with fewer than 30 affected individuals described. Affected patients are male, while carrier females are often asymptomatic. Cases have been reported from Germany, France, the Netherlands, Australia, and the United States.
Clinical description
The syndrome is characterized by an association of arthrogryposis multiplexa congenita and intellectual disability. Affected patients are born with severe contractures (arthrogryposis) and muscle weakness causing respiratory distress. Intellectual disability and delayed motor development are found in all patients. Facial weakness (ptosis) and bulbar weakness (feeding difficulty), characteristic dysmorphic facial features (possibly including long flat philtrum, low-set ears, high-arched palate, and carp-shaped mouth), and skeletal abnormalities (camptodactyly, hip dislocation, scoliosis, kyphosis, lordosis and pes equinovarus) have been reported. Other neurological signs may include spasticity and seizures. Heterozygous female carriers may also be affected, but to a lesser degree (intellectual disability, distal muscle weakness, camptodactyly, joint contractures, and pes equinovarus).
Etiology
Intellectual disability-developmental delay-contractures syndrome is caused by mutations in the ZC4H2 gene (Xq11.1) that is presumed to play a role in neuronal function during fetal growth.
Genetic counseling
The disorder follows an X-linked recessive pattern on inheritance. Simplex cases are also found. Genetic counseling should be provided to affected families.

                            Last update: 
                            January 2015
Intellectual disability-dysmorphism-hypogonadism-diabetes mellitus syndrome (ORPHA:3044)
A rare, genetic, syndromic intellectual disability disorder characterized by mild to moderate intellectual disability, facial dysmorphism (including a long face, deep-set eyes, narrow-based, broad nose with nostril colobomata, mandibular prognathism), hypergonadotrophic hypogonadism, eunuchoid habitus, diabetes mellitus type 1, and epilepsy. There have been no further descriptions in the literature since 1990.
Intellectual disability-epilepsy-extrapyramidal syndrome (ORPHA:468620)
A rare genetic neurological disorder characterized by hypotonia, delayed motor development, dyskinesia of the limbs, intellectual disability with impaired speech development, seizures, autistic features, stereotypic movements, and sleep disturbance. Onset of symptoms is in infancy. Bilateral abnormalities in the putamen on brain MRI have been reported in some patients.
Intellectual disability-expressive aphasia-facial dysmorphism syndrome (ORPHA:436151)
A rare genetic syndromic intellectual disability characterized by moderate to severe intellectual deficiency, language deficit (completely absent or significantly impaired speech), and distinctive facial dysmorphism (long face, straight eyebrows, and, less frequently, low-set ears and café-au-lait spots). Additional, variably observed features include motor delays, behavioral difficulties, and seizures.
Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency (ORPHA:404440)
A rare, syndromic intellectual disability characterized by intellectual disability of various severity, hypotonia, feeding difficulties, dysmorphic features, autism and behavioral issues. Growth retardation, congenital heart anomalies, gastrointestinal and genitourinary defects have been rarely associated.
Intellectual disability-facial dysmorphism-hand anomalies syndrome (ORPHA:370010)
Intellectual disability-facial dysmorphism-hand anomalies syndrome is a rare syndromic intellectual disability disorder characterized by moderate intellectual disability, variable hand abnormalities (including brachydactyly, cutaneous and osseous syndactyly), and facial dysmorphism that includes short palpebral fissures, bulbous nasal tip, thin upper and lower vermilion and broad, pointed chin. Other features, including obesity, microcephaly, short stature and a grimacing smile may be observed.
Intellectual disability-hyperkinetic movement-truncal ataxia syndrome (ORPHA:369847)
A rare, genetic, syndromic intellectual disability disease characterized by global developmental delay, microcephaly, mild to moderate intellectual disability, truncal ataxia, trunk and limb, or generalized, choreiform movements, and elevated serum creatine kinase levels. Variably associated features include mild cerebral atrophy, muscular weakness or hypotonia in early childhood, and/or seizures. Ocular abnormalities (e.g. exophoria, anisometropia, amblyopia) have been reported.
Intellectual disability-hypoplastic corpus callosum-preauricular tag syndrome (ORPHA:1495)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by psychomotor and growth delay, severe intellectual disability, microcephaly, and hypoplastic corpus callosum. Additional reported manifestations include increased muscle tonus, seizures, cardiac anomalies, recurrent bronchopneumonia, camptodactyly, preauricular skin tag, and dysmorphic facial features (such as broad forehead, hypertelorism, flat nasal bridge, anteverted nostrils, and prominent ears), among others.
Intellectual disability-hypotonia-brachycephaly-pyloric stenosis-cryptorchidism syndrome (ORPHA:314575)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism (brachycephaly resulting from craniosynostosis, frontal bossing, downslanting palpebral fissures, large and low-set ears, depressed nasal bridge, high-arched, wide palate, thin upper lip), impaired neurological development with intellectual disability, hypotonia, pyloric stenosis, pectus excavatum, bilateral cryptorchidism and short stature.
Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome (ORPHA:457279)
A rare, syndromic intellectual disability characterized by hypotonia, global developmental delay, limited or absent speech, intellectual disability, macrocephaly, mild dysmorphic features, seizures and autism spectrum disorder. Associated ophthalmologic, heart, skeletal and central nervous system anomalies have been reported.
Intellectual disability-muscle weakness-short stature-facial dysmorphism syndrome (ORPHA:457365)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by intellectual disability, developmental delay, delayed bone age, short stature, generalized muscle weakness, and dysmorphic facial features (such as high arched eyebrows, downslanting palpebral fissures, prominent nose, and narrow palate and mouth). Additional reported manifestations include blue sclerae, ophthalmoplegia, and intention tremor. Brain imaging may show white matter abnormalities.