TaoMedAI/RareMedData huggingface dataset:
Isolated tibial hemimelia (ORPHA:93322)
A rare congenital limb formation characterized by partial or complete absence of the tibia with a relatively intact fibula.
Epidemiology
Tibial hemimelia incidence is reported to be 1/1,000,000.
Clinical description
The disorder presents with a shortened lower limb and deformities at the knee, foot and ankle. The fibula is always present and may be quite normally formed or dysplastic, might be migrated proximally or can be hypertrophied to match a hypoplastic tibia. The tibia can be shortened, partially absent or completely absent. The quadriceps muscle and patella may be normally formed, deficient or absent, which is an important factor regarding reconstruction. Similarly, the cruciate and collateral ligaments may be present or absent. The knee may fully extend or have a flexion contracture or dislocation. The foot can show duplication or deficiency of the medial rays and can be in equinus or equino-varus. Tibial hemimelia is found bilateral in approximately 30%. The degree of dysplasia and type may vary significantly between sides. Unilateral cases have a leg length discrepancy. Various classifications are published, with early classification based on radiographic appearance, while later included the status of knee motion and also the cartilaginous anlage. The most recent classification additionally focuses on prognosis and treatment. Associated anomalies include congenital femoral deficiency, bifid femur, radial dysplasia, lobster claw deformity, hand syndactyly, polydactyly, triphalagism, missing fingers or toes, hip dysplasia, hip dislocation, hemivertebrae and myelomeningocele. The disorder is associated with several syndromes. Werner's syndrome, Gollop-Wolfgang, chromosome 8q deletion, Langer-Giedion syndrome or type II tricho-rhino-phalangeal syndrome (TRPS II) may also be responsible for the disorder.
Etiology
The etiology is unknown.
Diagnostic methods
Diagnosis is based on clinical and radiological findings.
Antenatal diagnosis
Prenatal diagnosis using ultrasound is possible.
Genetic counseling
Although the majority of cases with tibial hemimelia are sporadic, affected families with possible autosomal dominant or autosomal recessive inheritance have been reported.
Management and treatment
Surgical correction is generally possible for most subtypes. However, in cases with absent patella and/or no quadriceps function a through-knee amputation is usually recommended. The functional result after reconstruction mostly depends on knee stability and the position of the foot. Reconstruction of more severe types includes multiple surgeries and residual knee-instability requiring bracing might persist. Reconstruction versus amputation must be discussed with the family. Associated ray duplications on the foot need to be addressed.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Pr Sebastian FARR  - Pr Christof RADLER
Isolated tibio-fibular synostosis (ORPHA:295028)
Tibio-fibular synostosis is a rare, non-syndromic limb malformation characterized by fusion of the proximal or distal tibial and fibular metaphysis and/or diaphysis, frequently associated with distal positioning of the proximal tibiofibular joint, leg length discrepancy, bowing of the fibula, and valgus deformity of the knee.
Isolated tracheoesophageal fistula (ORPHA:454750)
A rare, congenital, esophageal malformation characterized by the presence of an abnormal connection between the esophagus and the trachea (typically occurring in the lower cervical or upper thoracic area and taking an oblique path upward to trachea), without concomitant esophageal atresia. Depending on the size of the lumen, presentation varies from neonatal episodes of choking and cyanosis on feeding to subtle symptoms of wheezing and recurrent respiratory infections in childhood or early adulthood.
Isolated unilateral hemispheric cerebellar hypoplasia (ORPHA:269218)
Isolated unilateral hemispheric cerebellar hypoplasia is a rare, non-syndromic cerebellar malformation characterized by loss of volume in the right or left cerebellar hemisphere, with intact vermis and no other neurological anomalies (i.e. normal cerebral hemispheres, fourth ventricle, pons, medulla and midbrain). Patients may be asymptomatic or may present developmental and speech delay, hypotonia, abnormal ocular movements, persistent headaches and/or peripheral vertigo and ataxia. Neurological examination is otherwise normal.
Isosporiasis (ORPHA:472)
Isosporiasis (also known as cystoisosporiasis) is an exclusively human parasitosis occurring mainly in the tropics and subtropics, due to infection with Isospora belli (through ingestion of contaminated food), that is frequently asymptomatic or that can cause fever and diarrhea, but that is usually a self-limiting condition in the immunocompetent. HIV-positive individuals are particularly at risk of suffering from symptomatic isosporiasis and can manifest with a more severe clinical course of chronic diarrhea and severe weight loss.
Isotretinoin syndrome (ORPHA:2305)
A rare tetrogenic embryofetopathy due to exposure to isotretinoin, an oral synthetic vitamin A derivative, which is used to treat severe recalcitrant cystic acne. Exposure to isotretinoin during the first trimester of pregnancy has been associated with an increased risk of spontaneous abortions and severe birth defects including serious craniofacial (microcephaly, asymmetric crying facies, microphthalmia, developmental abnormalities of the external ear, ocular hypertelorism), cardio vascular (conotruncal heart defects, aortic arch abnormalities), and central nervous system (hydrocephalus, microcephaly, lissencephaly, Dandy-Walker malformation, cognitive deficit) anomalies and thymic aplasia.
Isotretinoin-like syndrome (ORPHA:2306)
Isotretinoin-like syndrome is a phenocopy of the isotretinoin embryopathy.
Epidemiology
It has been described in six male patients, three of them being sibs born to nonconsanguineous parents.
Clinical description
It is characterized by the same anomalies as those described after maternal treatment with the drug isotretinoin (a vitamin A analog used for treatment of acne): malformations of the face (small, malformed, or missing ears, micrognathia, cleft palate), conotruncal heart defects, aortic arch anomalies, and central nervous system anomalies (hydrocephalus and posterior fossa abnormalities).
Etiology
The etiology is unknown.
Diagnostic methods
Diagnosis may be suspected in patients with a conotruncal heart and ear anomalies. Computed tomography of the temporal bone may reveal agenesis of the external auditory canals and bilateral ossicular chain abnormalities.
Antenatal diagnosis
Prenatal diagnosis may be performed by ultrasonography with careful examination of facial and cardiac structures.
Genetic counseling
As the syndrome has only been reported in males, X-linked recessive inheritance is possible, but autosomal recessive inheritance cannot be ruled out.
Prognosis
Survival may be influenced by the severity of the heart defect and no data are available on long term prognosis.

                            Last update: 
                            October 2006
ISPD-related limb-girdle muscular dystrophy R20 (ORPHA:352479)
A rare subtype of autosomal recessive limb-girdle muscular dystrophy disorder characterized by infantile to childhood-onset of slowly progressive, principally proximal, shoulder and/or pelvic-girdle muscular weakness that typically presents with positive Gowers' sign and is associated with elevated creatine kinase levels, hyporeflexia, joint and achilles tendon contractures, and muscle hypertrophy, usually of the thighs, calves and/or tongue. Other highly variable features include cerebellar, cardiac and ocular abnormalities.
ITM2B amyloidosis (ORPHA:439254)
A rare, neurodegenerative disease characterized by progressive dementia and ataxia, widespread cerebral amyloid angiopathy and parenchymal amyloid deposition. Two subtypes have been identified, ABri amyloidosis and ADan amyloidosis.
ITPA-related lethal infantile neurological disorder with cataract and cardiac involvement (ORPHA:457375)
A rare, genetic, neurometabolic disease characterized by early onset encephalopathy with progressive microcephaly, severe global development delay, seizures, hypotonia, feeding difficulties, variable cardiac abnormalities, and cataracts. Brain MRI shows distinct pattern with high T2 signal and restricted diffusion in the posterior limb of the internal capsule in combination with delayed myelination and progressive cerebral atrophy. The disease is typically fatal.
IVIC syndrome (ORPHA:2307)
IVIC syndrome is a very rare genetic malformation syndrome characterized by upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral non-progressive mixed hearing loss.
Epidemiology
Prevalence of IVIC is not known. To date, four affected families from Venezuela, Italy, Hungary, and Turkey (discordant monozygotic twins) have been described.
Clinical description
Asymmetrical upper limbs are a characteristic clinical manifestation. Thumb involvement is the most typical clinical manifestation and can range from absence or hypoplasia to the presence of a triphalangic thumb. Other upper limb anomalies include radial ray defects and carpal bone fusion. Upper limbs may be severely malformed. Extraocular motor disturbances and hearing loss of variable severity have also been reported. Some affected individuals have been reported to have mild thrombocytopenia, leukocytosis, shoulder girdle hypoplasia, cardiac involvement, kidney malrotation, intermediate anorectal malformation (see this term), or rectovaginal fistula. The clinical presentation is highly variable but lower limbs are normal. There have been reports of sudden death.
Etiology
The syndrome has been linked to mutations in the SALL4 gene (20q13.2) encoding a transcription factor involved in the maintenance and self-renewal of embryonic and hematopoietic stem cells. Okihiro syndrome (see this term) is a disorder allelic to IVIC syndrome.
Genetic counseling
IVIC syndrome is inherited in an autosomal dominant manner. Genetic counseling should be offered to affected families, informing them of the 50% risk of offspring inheriting the disease-causing mutation and therefore being affected with the syndrome.

                            Last update: 
                            October 2014


                            - Expert reviewer(s): 
                            Pr Giovanni NERI
Jackson-Weiss syndrome (ORPHA:1540)
Jackson-Weiss syndrome (JWS) is a rare genetic disorder characterized by foot malformations (tarsal and metatarsal fusions; short, broad, medially deviated great toes) and in some patients craniosynostosis with facial anomalies. Hands are normal in affected patients.
Jalili syndrome (ORPHA:1873)
Jalili syndrome is characterized by the association of amelogenesis imperfecta (AI; see this term) and cone-rod retinal dystrophy (CORD; see this term).
Epidemiology
It has been described in only one family with 29 affected individuals.
Clinical description
AI is a generic term for an inherited group of dental diseases in which the common clinical feature is an abnormality of tooth enamel. The enamel may be thin but normal, and/or hypomineralized. CORD is a rare retinal disorder that leads to an initial loss of central vision, color vision and photophobia before the age of 10 years with subsequent night blindness and visual field restriction.
Etiology
Mutations in the CNNM4 gene (2q11.2), which is implicated in metal ion transport, have been identified in several families.
Genetic counseling
Jalili syndrome is transmitted in an autosomal recessive manner.

                            Last update: 
                            April 2009
Japanese encephalitis (ORPHA:79139)
Japanese encephalitis is an arboviral disease (i.e. a disease due to a virus transmitted by an arthropod).
Epidemiology
The estimated annual incidence of the disease is 1/160 000 but it is 20 times higher in endemic areas. It mainly occurs in rural areas of China, Korea and Japan, in sub-tropical regions of Asia, and in some regions of Oceania. Imported cases are exceptional. The disease is symptomatic in 1-20/1000 infections, and children and young adults are predominantly affected.
Clinical description
After an incubation period of four to 14 days, infected individuals present with signs ranging from moderate with a headache and low-grade fever to more severe infection with high fever, meningeal syndrome (neck stiffness, vomiting), disorientation and sometimes tremors or coma.
Etiology
The disease is caused by a flavivirus spread by wild birds, amplified by domestic pigs, and transmitted to humans mainly by a mosquito of the genus Culex.
Management and treatment
There is no specific treatment, but intensive supportive therapy should be provided. A vaccine is available, but its prescription should be adapted to each case and depends on the risks of transmission when travelling to endemic areas (length of the stay, transmission season, visits to rural areas).
Prognosis
The disease, when it is symptomatic, can leave neurological sequelae and leads to death in 25 to 30% of the cases.

                            Last update: 
                            September 2006
Jawad syndrome (ORPHA:313795)
Jawad syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by congenital microcephaly wih facial dysmorphism (sloping forehead, prominent nose, mild retrognathia), moderate to severe, non-progressive intellectual disability and symmetrical digital malformations of variable degree, including brachydactyly of the fifth fingers with single flexion crease, clinodactyly, syndactyly, polydactyly and hallux valgus. Congenital anonychia and white café au lait-like spots on the skin of hands and feet are also associated.
Jejunal neuroendocrine tumor (ORPHA:100077)
Jejunal neuroendocrine tumor is a rare, primary, malignant, epithelial neoplasm of the small intestine arising from enterochromaffin cells in the jejunum. Clinical behavior depends on the histologic grade, but initially it is generally characterized by vague abdominal symptoms (cramping, bloating, diarrhea) with insidious onset, although sometimes it could present with signs of bowel obstruction/perforation or gastrointestinal bleeding. Diagnosis in advanced stages with regional or distant spread is common, but signs of carcinoid syndrome (flushing, sweating, diarrhea) are usually not apparent until hepatic metastasis has occurred.
Jeune syndrome (ORPHA:474)
Jeune syndrome, also called asphyxiating thoracic dystrophy, is a short-rib dysplasia characterized by a narrow thorax, short limbs and radiological skeletal abnormalities including 'trident' aspect of the acetabula and metaphyseal changes.
Epidemiology
Annual incidence at birth is unknown but is estimated to be 1-5/500,000.
Clinical description
The syndrome is recognizable during the antenatal period or at birth. In rare cases, postaxial polydactyly may also be present. The narrow thorax may cause neonatal respiratory failure, and may be associated with persistent respiratory manifestations. Some cases are severe while others have a benign course. The growth rate is variable but may be almost normal. Hepatic and renal failure has been reported in rare cases (liver fibrosis or nephronophthisis) occurring at any age. Retinal pigmentary degeneration could also be observed. Intellectual development is normal.
Etiology
The molecular basis of the syndrome has been partially elucidated indicating involvement of the IFT80 (3q25.33), DYNC2H1 (11q22.3), WDR19 (4p14) and TTC21B (2q24.3) genes, each encoding an intraflagellar transport protein, which confirms that Jeune syndrome belongs to the ciliopathies group. Mutations in other genes may also be implicated in the disease and remain to be identified.
Diagnostic methods
The diagnosis is based on radiologic findings: ribs are short and the pelvis has an abnormal morphology, with a horizontal acetabular roof and a trident aspect formed by a median protrusion and two lateral spurs. Hands are normal or short with possible cone-shaped epiphyses in the phalanges.
Differential diagnosis
Differential diagnosis should include thoracolaryngopelvic dysplasia, Ellis-van Creveld syndrome, Sensenbrenner syndrome and paternal uniparental disomy of chromosome 14 (see these terms).
Antenatal diagnosis
Molecular diagnosis must be confirmed in the proband before proposing prenatal molecular testing. In other cases, only a careful antenatal ultrasound examination can detect the disease.
Genetic counseling
The syndrome is transmitted as an autosomal recessive trait. The recurrence risk is 25% for every pregnancy after the birth of an affected child.
Management and treatment
Treatment consists of management of respiratory infections, which may lead to severe complications. Renal and hepatic function should be monitored regularly, and retinal examination performed.
Prognosis
Prognosis is highly variable depending of the visceral associated diseases, and the risk of severe respiratory complications decreases after 2 years of age.

                            Last update: 
                            December 2011


                            - Expert reviewer(s): 
                            Dr Geneviève BAUJAT
Johnson neuroectodermal syndrome (ORPHA:2316)
Johnson neuroectodermal syndrome is characterised by alopecia, anosmia or hyposmia, conductive deafness with malformed ears and microtia and/or atresia of the external auditory canal, and hypogonadotropic hypogonadism.
Epidemiology
So far, less than 30 cases have been described in the literature.
Clinical description
Other variable features include a congenital heart defect, facial asymmetry, intellectual deficit, cleft palate, choanal stenosis and an increased tendency for dental caries.
Etiology
The aetiology is unknown but the combination of developmental anomalies present in patients with this syndrome is suggestive of an embryological defect in the formation of the neuroectodermal derivatives of cephalic neural crest.
Genetic counseling
The syndrome is transmitted as an autosomal dominant trait.

                            Last update: 
                            October 2006
Joubert syndrome with hepatic defect (ORPHA:1454)
Joubert syndrome with hepatic defect is a very rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with congenital hepatic fibrosis (CHF).
Epidemiology
Prevalence is unknown.
Clinical description
The age of onset and severity of hepatic manifestations are variable. Some patients may also present chorioretinal or optic nerve colobomas and nephronophthisis (NPH), but these are not mandatory features.
Etiology
Over 70% of cases are due to mutations in the TMEM67 gene (8q22.1).
Genetic counseling
Transmission is autosomal recessive.

                            Last update: 
                            July 2011


                            - Expert reviewer(s): 
                            Dr Francesco BRANCATI  - Pr Bruno DALLAPICCOLA  - Pr Enza Maria VALENTE
Joubert syndrome with Jeune asphyxiating thoracic dystrophy (ORPHA:397715)
A rare genetic developmental defect during embryogenesis characterized by the association of the classic features of Joubert syndrome (congenital midbrain-hindbrain malformations causing hypotonia, abnormal breathing and eye movements, ataxia and cognitive impairment) together with the skeletal anomalies of Jeune asphyxiating thoracic dystrophy (short ribs, long and narrow thorax causing respiratory failure, short-limbs, short stature, and polydactyly). Additional variable manifestations include cystic kidneys, liver fibrosis, and retinal dystrophy.
Joubert syndrome with ocular defect (ORPHA:220493)
Joubert syndrome with ocular defect is, along with pure JS, the most frequent subtype of Joubert syndrome and related disorders (JSRD, see these terms) characterized by the neurological features of JS associated with retinal dystrophy.
Epidemiology
Prevalence is unknown.
Clinical description
Age of onset and severity of retinal involvement are variable, ranging from congenital blindness in patients with Leber congenital amaurosis (LCA, see this term) to progressive retinopathy with partial conservation of vision.
Etiology
To date, the most frequently mutated gene in this subtype is AHI1 (6q23.2), which accounts for about 20% of cases, following autosomal recessive inheritance.

                            Last update: 
                            July 2011


                            - Expert reviewer(s): 
                            Dr Francesco BRANCATI  - Pr Bruno DALLAPICCOLA  - Pr Enza Maria VALENTE
Joubert syndrome with oculorenal defect (ORPHA:2318)
A rare subtype of Joubert syndrome (JS) and related disorders (JSRD) characterized by the neurological features of JS associated with both renal and ocular disease.
Epidemiology
Prevalence is unknown.
Clinical description
Patients present retinal involvement (manifesting with either Leber congenital amaurosis (LCA, see this term), or progressive retinal dystrophy) and nephronophthisis (NPH, usually juvenile). Retinal involvement is present at birth (LCA) or may manifest later in life. Juvenile NPH usually becomes clinically symptomatic towards the late first decade or the early second decade of life.
Etiology
About 50% of patients carry mutations in the CEP290 gene (12q21.33), transmitted in an autosomal recessive manner.

                            Last update: 
                            July 2011


                            - Expert reviewer(s): 
                            Dr Francesco BRANCATI  - Pr Bruno DALLAPICCOLA  - Pr Enza Maria VALENTE
Joubert syndrome with renal defect (ORPHA:220497)
Joubert syndrome with renal defect is a rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with renal disease, in the absence of retinopathy.
Epidemiology
Prevalence is unknown.
Clinical description
In most cases, renal disease manifests as juvenile nephronophthisis, with onset of clinical symptoms in the late first/early second decade of life, although in rare cases there may be infantile NPH, with onset in the first years of life.
Etiology
The most commonly mutated genes in this subtype are NPHP1 (2q13) and RPGRIP1L (16q12.2) with autosomal recessive inheritance.

                            Last update: 
                            July 2011


                            - Expert reviewer(s): 
                            Dr Francesco BRANCATI  - Pr Bruno DALLAPICCOLA  - Pr Enza Maria VALENTE
Juberg-Hayward syndrome (ORPHA:2319)
Juberg-Hayward syndrome is a polymalformative syndrome that associates multiple skeletal anomalies with microcephaly, facial dysmorphism, urogenital anomalies and intellectual deficit.
Junctional epidermolysis bullosa inversa (ORPHA:79405)
A rare intermediate form of junctional epidermolysis bullosa characterized by congenital blistering and erosions confined to intertriginous skin sites, the esophagus, groin, and perineum. Blistering is usually severe and lesions may heal with atrophic scarring and milia formation. Extracutaneous manifestations include nail dystrophy, enamel hypoplasia and dental caries, oral, esophageal and vaginal blisters and erosions.
Jung syndrome (ORPHA:2321)
A rare, congenital malformation syndrome characterized by the association of anterior ocular chamber cleavage disorder with developmental delay, short stature and congenital hypothyroidism. Additional manifestations include cerebellar hypoplasia, tracheal stenosis, narrow external auditory meatus, and hip dislocation. There have been no further description in the literature since 1995.