TaoMedAI/RareMedData huggingface dataset:
Isolated bilateral hemispheric cerebellar hypoplasia (ORPHA:269221)
Isolated bilateral hemispheric cerebellar hypoplasia is a rare cerebellar malformation characterized by hypoplasia of both cerebellar hemispheres with no other cerebellar/cerebral anomaly or other associated clinical feature. Affected patients present with mild hypotonia with motor delay, mild cognitive impairment, language delay, visuospatial and verbal memory deficits, dysdiadochokinesis, intentional tremor, and possible presence of emotional fragility and mild depression.
Isolated biliary atresia (ORPHA:30391)
A rare, biliary tract disease characterized by progressive obliterative cholangiopathy of the intra- and extrahepatic bile ducts, occuring in the embryonic/ perinatal period, leading to severe and persistent neonatal jaundice and acholic stool.
Epidemiology
Biliary atresia (BA) prevalence at birth is 1/ 15,000-19,000 in Europe and North America.
Clinical description
Diagnosis is mostly made at 2-6 weeks of age, presenting with cholestasis, jaundice, acholia and possibly choluria and hepatomegaly, and sometimes vitamin K deficiency induced bleedings. Conjugated hyperbilirubinemia associated with an increase in γ-glutamyltransferase (GGT) are biochemical signs of the disease. The pathology is characterized by an ongoing inflammatory process of the entire biliary tree, although the disease is defined as an irreversible closure/ atresia of the extrahepatic bile ducts. In 10-20% of cases, biliary atresia is associated with other malformations (syndromic biliary atresia).
Etiology
The etiology is yet to be explained, but it is believed that it can be the result of the interaction of genetic, environmental, immune, and infectious factors, individually or in combination.
Diagnostic methods
Preoperative evaluation may include abdominal ultrasound, hepatobiliary scintigraphy, percutaneous liver biopsy, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography (MRCP). However, the definitive diagnosis is confirmed only by cholangiography.
Differential diagnosis
The differential diagnosis include other causes of neonatal cholestasis, for example infections, Alagille syndrome, alpha-1-antitrypsin deficiency, progressive familiar intrahepatic cholestasis (PFIC) and hormonal deficiencies.
Antenatal diagnosis
Signs of biliary atresia on prenatal ultrasonography has rarely been reported.
Genetic counseling
The disease is not yet identified to be hereditary. The genetic counseling is therefore not possible.
Management and treatment
Kasai portoenterostomy is the gold standard treatment, consisting in total extraction of the hilar fibrosis and subsequent biliary-enteric anastomosis, with favorable results in a maximum of 50% of cases, in which there is total restitution of the biliary drainage and normalization of total bilirubin levels.
Prognosis
The main prognostic factors to short- and long-term survival after surgery include age at surgery, type of biliary atresia, and experience of the center. Out of the possible complications, the most common are cholangitis, portal hypertension, and ongoing deterioration of the liver function with cirrhosis, leading to end-stage failure. Early liver transplantation is required in about 50% of the cases. Very long term survival with native liver decreases to about 25%.

                            Last update: 
                            October 2020


                            - Expert reviewer(s): 
                            Dr Björn FISCHLER | RARE-LIVER* - Pr Claus PETERSEN | RARE-LIVER*


                                * European Reference Network
Isolated blepharochalasis (ORPHA:519390)
A rare palpebral disorder characterized by recurrent episodes of painless eyelid edema. It usually occurs bilaterally, typically affects the upper eyelids, and may manifest as a hypertrophic form resulting in orbital fat herniation through a weakened orbital septum, or an atrophic form with atrophy of redundant eyelid skin and superior nasal fat pads. Additional findings are formation of pseudoepicanthal folds, lacrimal gland prolapse, or ptosis.
Isolated bone marrow mastocytosis (ORPHA:158778)
A rare subtype of indolent systemic mastocytosis characterized by isolated bone marrow involvement without skin lesions, low burden of neoplastic mast cells, and often normal or near normal serum tryptase levels. The KIT D816V mutation is present in the majority of cases.
Isolated cerebellar agenesis (ORPHA:1398)
A rare non-syndromic central nervous system malformation characterized by complete or near-complete absence of the cerebellum with a normal sized posterior fossa, possibly accompanied by hypoplasia of the brainstem. The clinical picture is highly variable, but typically includes ataxia, dysarthria, tremor, dysmetria, dysdiadochokinesia, and oculomotor abnormalities, in addition to impaired mental, motor, and language development and intellectual disability.
Isolated cerebellar vermis agenesis (ORPHA:269203)
A rare, congenital, cerebellar malformation disorder characterized by complete or partial cerebellar vermis agenesis, with no other associated malformations or anomalies. Patients may be asymptomatic, although psychomotor delay, hypotonia and incoordination are usually associated. Additional variable manifestations include intellectual disability, oculomotor abnormalities (such as nystagmus, impaired smooth pursuit, impaired saccades, strabismus, ptosis, and oculomotor apraxia), retinopathy, abnormal visual evoked potentials, ataxia, episodic hyperpnea, and delayed gait acquisition, as well as delayed speech and language development.
Isolated cerebellar vermis hypoplasia (ORPHA:199630)
Isolated cerebellar vermis hypoplasia is a rare, non-syndromic cerebellar malformation characterized by an underdeveloped cerebellar vermis. Patients may present a variable phenotype ranging from normal neurodevelopment to motor and/or language delay, variable degrees of cognitive impairment, hypotonia, equilibrium disturbances, static/dynamic ataxia, oculomotor abnormalities, epilepsy and/or clumsiness. Behavioral disorders such as attention deficit hyperactivity disorder and generalized anxiety have also been reported. Brain MRI may reveal diffuse or selective (mostly posterior) vermian cerebellar hypoplasia and EEG may show focal paroxysms.
Isolated cleft lip (ORPHA:199302)
Isolated cleft lip is a fissure type embryopathy extending from the upper lip to the nasal base.
Epidemiology
The annual incidence is 1/4,000 to 1/10,000 births with major variation occurring between geographic locations and ethnic groups. Cleft lip is twice as common in boys as girls and is seen more frequently on the left side.
Clinical description
The cleft is paramedian and located at the level of the philtrum. It presents as a cutaneous, muscular and mucosal interruption from the lip to the nasal base, associated with nostril and nasal septum deformations. Clinical forms range from a simple notch in the upper lip to a complete cleft lip with an opening at the base of the nostril without reaching as far as the gum (alveolar ridge).
Etiology
This embryopathy appears between the 5th and 12th week of pregnancy due to a failure in the fusion of the frontal processes (fronto-nasal process, medial and lateral nasal processes, maxillary process). Cleft lip is an isolated, non-syndromic anomaly in 70% of cases. The remaining 30% of cases are seen in at least 300 syndromes where cleft lip is just one of the featured anomalies. Non-syndromic clefts are possibly caused by a combination of genetic and environmental factors. Factors such as the exposure to teratogenic substances during pregnancy (alcohol, tobacco or drugs) can have an influence on genetic susceptibility.
Diagnostic methods
The diagnosis is clinical.
Differential diagnosis
The presence of associated malformations allows for differentiation between isolated and syndromic forms.
Antenatal diagnosis
Antenatal diagnosis is often possible with a prenatal ultrasound. The case is submitted to a multidisciplinary center for prenatal diagnosis in order to establish if it is an isolated anomaly.
Management and treatment
Management requires multidisciplinary medical and surgical intervention from birth until the end of development. It involves primary surgery sometimes followed by secondary maxillo-facial and plastic surgery. An initial treatment timeline is established during the neonatal period. Secondary management is adapted to the child's age and based on morphological and functional problems that may arise during growth and development. Breathing difficulties can occur due to the nostril anomaly and the deviation of the vomer, of the nasal septum and to the turbinate hypertrophy. Secondary surgery of the nose can be performed to improve appearance and function.
Prognosis
Prognosis is dependent on the quality of initial management and the regular follow-up by an experienced interdisciplinary team until the child is fully grown. Cleft lip can have functional (morphological, respiratory), esthetic and psychological consequences that require management in a specialized health center.

                            Last update: 
                            December 2011


                            - Expert reviewer(s): 
                            Dr Eva GALLIANI  - Pr Marie-Paule VAZQUEZ
Isolated complex I deficiency (ORPHA:2609)
Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome (see these terms).
Isolated complex III deficiency (ORPHA:1460)
Isolated complex III deficiency is a rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by a wide spectrum of clinical manifestations ranging from isolated myopathy or transient hepatopathy to severe multisystem disorder (that may include hypotonia, failure to thrive, psychomotor delay, cardiomyopathy, encephalopathy, renal tubulopathy, hearing impairment, lactic acidosis, hypoglycemia and other signs and symptoms).
Isolated congenital adermatoglyphia (ORPHA:289465)
Isolated congenital adermatoglyphia is a rare, genetic developmental defect during embryogenesis disorder characterized by the lack of epidermal ridges on the palms and soles, resulting in the absence of fingerprints, with no other associated manifestations. It is associated with a reduced number of sweat gland openings and reduced transpiration of palms and soles.
Isolated congenital alacrima (ORPHA:91416)
Congenital alacrima is characterised by deficient lacrimation (ranging from a complete absence of tears to hyposecretion of tears) that is present from birth.
Epidemiology
Prevalence is unknown.
Genetic counseling
Transmission is usually autosomal recessive, but dominant transmission has also been described.
Management and treatment
Artificial tears are the first treatment option, needed to avoid corneal sequelae.

                            Last update: 
                            April 2007
Isolated congenital anonychia (ORPHA:79143)
Isolated congenital anonychia is characterized by nail abnormalities ranging from onychodystrophy (dystrophic nails) to anonychia (absence of nails). Onychodystrophy-anonychia has been described in at least four generations of a family with male-to-male transmission, suggesting autosomal dominant transmission. Anonychia has been described in approximately less than 20 cases; it is likely to be transmitted as an autosomal recessive trait. Total anonychia congenita, in which all the fingernails and toenails are absent, may have an autosomal dominant inheritance pattern.
Isolated congenital anosmia (ORPHA:88620)
A rare otorhinolaryngologic disease characterized by total or partial anosmia at birth. The anosmia is caused by a defect in the development of the olfactory bulbs or by replacement of the olfactory epithelium by respiratory epithelium. Isolated congenital anosmia is found in some parents of individuals with Kallman syndrome.
Isolated congenital auditory ossicle malformation (ORPHA:162526)
Isolated congenital auditory ossicle malformation is a rare, congenital, middle ear anomaly characterized by, usually unilateral and sporadic, variations in the number, size and/or configuration of the ossicles, with no tympanic membrane and external ear abnormalities and no history of trauma or infection. Patients frequently present late, after schooling has started, with non-progressive, conductive hearing loss often associated with speech delay and poor school performance.
Isolated congenital breast hypoplasia/aplasia (ORPHA:180188)
A rare breast malformation characterized by congenital absence of breast and nipple (amastia), or nipple or mammary gland (athelia or amazia, respectively). It can be unilateral or bilateral and may occur as an isolated malformation or be associated with a syndrome or cluster of other anomalies.
Isolated congenital ectropion (ORPHA:99171)
Isolated congenital ectropion is a rare ocular disease characterized by congenital, unilateral or bilateral, lower or upper eyelid malposition with eversion of the margin due to a vertical shortage of skin, leading to exposure of the conjunctiva and sometimes the cornea. Chronic epiphora and exposure keratitis may be observed in severe cases.
Isolated congenital entropion (ORPHA:519386)
A rare eyelid malposition disorder characterized by congenital abnormal inversion of the eyelid towards the globe, potentially causing mechanical irritation of the ocular surface by the eyelashes, which may lead to corneal abrasion and scarring with visual impairment. Typical initial symptoms are foreign body sensation, redness, tearing, and ocular discharge.
Isolated congenital hepatic fibrosis (ORPHA:485426)
A rare parenchymal liver disease characterized by progressive fibrosis of the portal tracts due to arrest of maturation of the ductal plate of the intrahepatic bile ducts. Clinically, it may manifest as a portal hypertensive, cholangitic, mixed, or latent form. Onset of symptoms is mostly in adolescence or young adulthood. Hepatocellular function is relatively well preserved.
Isolated congenital hypoglossia/aglossia (ORPHA:141152)
A rare head and neck malformation characterized by congenital partial (hypoglossia) or total (aglossia) absence of the tongue. Patients present feeding and respiratory difficulties, as well as delayed speech development and slurred speech. Taste perception is not severely compromised. Associated features include a characteristic facies due to mandibular transverse arch deficiency, oligodontia, and malocclusion, among others.
Isolated congenital megalocornea (ORPHA:91489)
Isolated congenital megalocornea is a genetic, non-syndromic developmental defect of the anterior eye segment characterized by bilateral enlargement of the corneal diameter (>12.5 mm) and a deep anterior eye chamber, without an elevation in intraocular pressure. It can manifest with mild to moderate myopia as well as photophobia and iridodonesis (due to iris hypoplasia). Associated complications include lens dislocation, retinal detachment, presenile cataract development, and secondary glaucoma.
Isolated congenital microcephaly (ORPHA:199642)
A rare neurological disorder characterized by a reduced head circumference at birth with no gross anomalies of brain structure. It can be an isolated finding or it can be associated with seizures, developmental delay, intellectual disability, balance disturbances, hearing loss or vision problems.
Isolated congenital nasal pyriform aperture stenosis (ORPHA:162516)
A rare otorhinolaryngological malformation characterized by narrowing of the pyriform aperture (i. e. < 8 to 10 mm in a full-term infant) due to an overgrowth of the nasal process of the maxilla, resulting in potentially lethal nasal airway obstruction in the newborn. Depending on the degree of obstruction, clinical signs and symptoms include inspiratory stridor, respiratory distress, cyanosis, sternal retraction, ribcage asymmetry, and feeding difficulties.
Isolated congenital onychodysplasia (ORPHA:79144)
A rare isolated nail anomaly characterized by congenital unilateral or bilateral nail dysplasia (including micronychia, polyonychia, anonychia, hemionychrogryphosis, and malalignment) commonly involving the index fingers and/or other fingers or also toes, frequently associated with bony anomalies of the affected digits (such as Y-shaped bifurcation of the distal phalanx, brachymesophalangy, or syndactyly). The condition can be sporadic or familial.
Isolated congenital radial head dislocation (ORPHA:295032)
A rare congenital limb malformation characterized by mostly posterior, less frequently also anterior or lateral dislocation of the radial head from its position in the humeroradial joint. It is bilateral in the majority of cases and can occur as an isolated feature or in association with other congenital malformations and as part of a number of syndromes. The defect may at first cause only mild symptoms such as pain and limitation of flexion of the elbow, but may eventually lead to joint instability, dysplastic changes of the radial head, and arthritis.
Isolated congenital sclerocornea (ORPHA:91490)
A rare corneal disorder characterized by non-inflammatory, non-progressive, bilateral ingrowth of vascularized, opaque scleral tissue into the peripheral cornea, obliterating the corneoscleral limbus and scleral sulcus. The condition is not associated with other ocular abnormalities.
Isolated congenital syngnathia (ORPHA:141214)
Isolated congenital syngnathia is a very rare developmental defect during embryogenesis disorder characterized by varying degrees of congenital fusion (ranging from simple mucosal adhesions to extensive bony fusion) of mandible to maxilla that is not associated with any other malformations. Patients present with mouth opening limitation (which could range from severe to minimal restriction) that typically results in feeding, swallowing and/or respiratory difficulties which may lead to failure to thrive, malnutrition and/or temporomandibular joint ankylosis.
Isolated corpus callosum agenesis (ORPHA:200)
A rare non-syndromic cerebral malformation characterized by congenital partial or complete absence of the corpus callosum. Patients are often asymptomatic but may also present with intellectual disability, visual impairment, delayed speech development, seizures, feeding difficulties, impaired hand-eye coordination, and behavioral abnormalities. Patients may have a normal intelligence quotient while exhibiting specific cognitive deficits, such as reduced interhemispheric transfer of sensorimotor information, reduced cognitive processing speed, and deficits in complex reasoning and novel problem-solving.
Isolated cryptophthalmia (ORPHA:91396)
A rare congenital abnormality in which the eyelids are absent and skin covers the ocular bulb, which is often microphthalmic. A few cases of complete bilateral crytophthalmia have been described.
Isolated cytochrome C oxidase deficiency (ORPHA:254905)
A rare mitochondrial oxidative phosphorylation disorder characterized by a highly variable clinical phenotype, including a benign infantile mitochondrial type affecting mainly the skeletal muscle, a lethal infantile mitochondrial myopathy linked to severe metabolic acidosis and mitochondrial dysfunction in skeletal muscle and often also in heart, Leigh syndrome, which causes severe, early-onset, progressive, and fatal encephalopathy, and French-Canadian type Leigh syndrome, which affects mostly the skeletal muscle, but also brain and liver.
Isolated Dandy-Walker malformation (ORPHA:217)
A rare non-syndromic central nervous system malformation characterized by the association of three signs: hydrocephalus, partial or complete absence of the cerebellar vermis, and posterior fossa cyst contiguous with the fourth ventricle, presenting early in life with hydrocephalus, bulging occiput and posterior fossa signs such as cranial nerve palsies, nystagmus and ataxia.
Isolated delta-storage pool disease (ORPHA:248340)
Isolated delta-storage pool disease is a rare, isolated, constitutional thrombocytopenia disorder characterized by defective formation and/or malfunction of platelet dense granules, as well as melanosomes in skin cells, resulting in variable manifestations ranging from mild bleeding and easy bruising to moderate mucous/cutaneous hemorrhagic diathesis and bleeding complications after surgery.
Isolated distal symphalangism (ORPHA:3248)
Distal symphalangism is a very rare bone disorder characterized by ankylosis of the distal interphalangeal joints of the hands and/or feet.
Isolated distichiasis (ORPHA:99177)
Isolated distichiasis is a rare congenital eyelid anomaly characterized by an accessory row of eyelashes (that may be partial or complete) posterior to the normal row of cilia, at or close to the meibomian gland orifices, that is not associated with any other condition, and that may lead to ocular irritation and corneal damage if left untreated.
Isolated encephalocele (ORPHA:199647)
A rare, neural tube closure defect characterized by partial lacking of bone fusion, resulting in sac-like protrusions of the brain and the membranes that cover it through the openings in the skull. Protruding tissue may be located on any part of the head, but most often affects the occipital area. Depending in the size and location, encephalocele are often associated with neurological problems including intellectual disability, seizures, vision impairment, ataxia, and hydrocephalus.
Isolated femoral agenesis/hypoplasia (ORPHA:1987)
Congenital short femur is a rare malformation of variable severity ranging from mild hypoplasia to complete absence of the femur.
Isolated focal cortical dysplasia (ORPHA:65683)
Isolated focal cortical dysplasia is a rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disorder characterized by variable-sized, focalized malformations located in any part(s) of the cerebral cortex, which manifests with drug-resistant epilepsy (usually leading to intellectual disability) and behavioral disturbances. Abnormal MRI findings (e.g. abnormal white and/or grey matter signal, blurred gray-white matter junction, localized volume loss, cortical thickening, abnormal gyral pattern, abnormal hippocampus) and variable histopathologic patterns are associated.
Isolated focal non-epidermolytic palmoplantar keratoderma (ORPHA:448264)
A rare hereditary palmoplantar keratoderma characterized by focal hyperkeratotic lesions on the palms and soles. Histopathologic examination reveals prominent hyperkeratosis, thickened stratum spinosum with reduced stratum granulosum, disadhesion of cells in the suprabasal layers, elongation of rete ridges, and sparse lymphocyte infiltration in the dermis.
Isolated follicle stimulating hormone deficiency (ORPHA:52901)
A rare congenital hypogonadotropic hypogonadism characterized by hypogonadism due to selective deficiency of follicle stimulating hormone (FSH). Clinical manifestations are primary amenorrhea, absent or incomplete breast development, and infertility in women, and small testes, azoospermia, and infertility in men. Luteinizing hormone is elevated in the gonadotropin-releasing hormone stimulation test, while the FSH response is impaired.
Isolated foveal hypoplasia (ORPHA:519398)
A rare macular disorder characterized mostly by a variable degree of decreased visual acuity, jerk or pendular nystagmus, and typical ocular findings at imaging. The disease is usually bilateral. Rarely, nystagmus can be absent. Locally, the disease is characterized by underdeveloped foveal pit, absence of foveal pigmentation and/or foveal avascular zone, and persistence of inner retinal layers at the fovea, in absence of concomitant ocular or systemic pathology.