TaoMedAI/RareMedData huggingface dataset:
NUT midline carcinoma (ORPHA:443167)
A rare tumor characterized by a rapidly growing mass usually arising along the midline, defined by the presence of NUTM1 rearrangements. Histopathological examination shows a poorly differentiated carcinoma, often with evidence of squamous differentiation. Patients present with unspecific signs and symptoms due to mass effect, depending on the location. Extensive local invasion of adjacent structures, lymph node involvement, and distant metastatic disease are often present at the time of diagnosis. Prognosis is generally poor.
O'Sullivan-McLeod syndrome (ORPHA:99965)
A rare acquired motor neuron disease characterized by an initial unilateral weakness in the intrinsic hand muscles that eventually spreads to the opposite limb (with an asymmetrical distribution) and that has a very slow progression of muscular atrophy over a 20 year period.
Obesity due to CEP19 deficiency (ORPHA:397615)
A rare, genetic form of obesity characterized by morbid obesity, hypertension, type 2 diabetes mellitus and dyslipidemia leading to early coronary disease, myocardial infarction and congestive heart failure. Intellectual disability and decreased sperm counts or azoospermia have also been reported.
Obesity due to congenital leptin deficiency (ORPHA:66628)
Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia.
Epidemiology
It has been described in less than 30 patients.
Clinical description
Patients with congenital leptin deficiency are severely hyperphagic from early infancy and, although birthweight is normal, they rapidly become obese during early childhood. An increased susceptibility to infections has also been reported in these infants and appears to be associated with reduced numbers of circulating CD4+ T cells, and impaired T cell proliferation and cytokine release. Other features of the disorder include hyperinsulinaemia, advanced bone age, hypothalamic hypothyroidism and hypogonadotropic hypogonadism leading to a failure to undergo puberty.
Etiology
Leptin is an adipocyte-derived hormone that plays an important role in energy balance and appetite suppression. Whilst the majority of obese patients display hyperleptinaemia, patients with congenital leptin deficiency have undetectable levels of leptin in the serum. This absence of serum leptin is caused by homozygous frameshift or missense mutations in the ob gene (7q31.3) and is inherited as an autosomal recessive trait. However, a similar phenotype has been observed in three individuals from one consanguineous family who carried homozygous mutations in the gene encoding the leptin receptor (LEPR, 1p31).
Diagnostic methods
Family history, severe hyperphagia and early-onset obesity may lead to suspicion of a monogenic obesity syndrome. The diagnosis of congenital leptin deficiency can be confirmed by analysis of serum leptin levels or identification of mutations in the ob gene.
Management and treatment
Congenital leptin deficiency can be successfully treated with daily subcutaneous injections of recombinant human leptin, resulting in sustained positive effects on weight loss, reducing appetite, appropriate pubertal development and hyperinsulinaemia.
Prognosis
As a result, the prognosis for patients undergoing treatment appears to be excellent. However, misdiagnosed patients are at risk of developing the complications normally associated with severe obesity (in particular type 2 diabetes), with the prognosis being hampered further by an increased rate of mortality due to childhood infection.

                            Last update: 
                            May 2007


                            - Expert reviewer(s): 
                            Pr Sebastiano FILETTI
Obesity due to leptin receptor gene deficiency (ORPHA:179494)
A rare, genetic, non-syndromic, obesity disease characterized by severe, early-onset obesity, associated with major hyperphagia and endocrine abnormalities, resulting from leptin receptor deficiency.
Obesity due to melanocortin 4 receptor deficiency (ORPHA:71529)
Melanocortin 4 receptor (MC4R) deficiency is the commonest form of monogenic obesity identified so far. MC4R deficiency is characterised by severe obesity, an increase in lean body mass and bone mineral density, increased linear growth in early childhood, hyperphagia beginning in the first year of life and severe hyperinsulinaemia, in the presence of preserved reproductive function.
Epidemiology
The prevalence in the general population is probably around 1 in 2000. The prevalence of MC4R mutations has been estimated at between 0.5 and 1% in obese adults (body mass index >30) with higher values among populations with severe childhood-onset obesity and variability between ethnic groups.
Etiology
MC4R is a G protein-coupled receptor involved in the hypothalamic leptin-melanocortin signalling pathway. Activation of the MC4R plays a key role in the maintenance of energy homeostasis and is associated with suppression of food intake. The majority of patients described so far are carriers of heterozygous mutations in the MC4R gene (18q22). Rare homozygous carriers have been described and display a more severe phenotype. However, one homozygous patient with complete absence of MC4R function has been reported and did not display hyperinsulinaemia.
Diagnostic methods
The majority of MC4R deficient cases reported so far have been identified through genetic screening of large cohorts of obese patients, however, diagnosis may be suspected on the basis of the clinical features of the disorder and confirmed by detection of a MC4R mutation.
Genetic counseling
MC4R deficiency is transmitted in a codominant manner, with expressivity and penetrance varying between ethnic groups.
Management and treatment
At present, there is no specific treatment for MC4R deficiency. However, future development of small molecule MC4R agonists might lead to the generation of highly effective treatments for this disorder.
Prognosis
As with other forms of obesity, the prognosis is dependent on the complications present, with obese patients being at increased risk of cardiovascular disease, cancer and type 2 diabetes.

                            Last update: 
                            May 2007


                            - Expert reviewer(s): 
                            Pr Sebastiano FILETTI
Obesity due to prohormone convertase I deficiency (ORPHA:71528)
A rare genetic endocrine disease characterized by early onset of severe intractable diarrhea and intestinal malabsorption, followed by obesity and hormonal deficiencies due to insufficient activation of several prohormones, resulting in hypocortisolism, hypothyroidism, diabetes insipidus, hypogonadism, growth deficiency, and diabetes mellitus. Extent and age of onset of hormone deficiencies are variable between patients.
Obesity due to SIM1 deficiency (ORPHA:369873)
A rare, genetic form of obesity characterized by severe early-onset obesity, hyperphagia, and variable presence of cognitive impairment and behavioral disorder, including autistic spectrum behavior, impaired concentration and memory deficit. Some patients present with Prader-Willi-like features such as hypotonia, developmental delay, intellectual disability, short stature, hypopituitarism and dysmorphic facial features.
Obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome (ORPHA:88643)
Obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome is characterised by precocious obesity, congenital hypothyroidism, neonatal colitis, cardiac hypertrophy, craniosynostosis and developmental delay. It has been described in two brothers, one of whom died within the first month of life. The parents of the two children were nonconsanguineous and in good health, however, the pregnancies were complicated by a maternal HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelets). The mode of inheritance has not yet been clearly established.
Occipital pachygyria and polymicrogyria (ORPHA:280640)
A rare, genetic, cerebral malformation characterized by the presence of cortical smoothening with loss of secondary and tertiary gyri, associated with an excessive number of small, irregular gyri with increased cortical thickness, located in the occipital lobes. Patients usually present with seizures (including myoclonic-astatic, absence, atypical absence, vision loss, myoclonic-atonic, generalized tonic-clonic) and variable (absent to moderate) developmental and/or intellectual delay.
Occult macular dystrophy (ORPHA:247834)
Occult macular dystrophy is a rare, genetic retinal dystrophy disease characterized by bilateral progressive decline of visual acuity, due to retinal dysfunction confined only to the macula, associated with normal fundus and fluorescein angiograms and severly attenuated focal macular and multifocal electroretinograms.
Occupational allergic alveolitis (ORPHA:99909)
Occupational allergic alveolitis designates a hypersensitivity pneumonitis (see this term) resulting from the inhalation of an antigen to which an individual has been previously sensitized in his/her occupational environment. Symptoms vary depending on the antigen and the form (acute, subacute, chronic) of the disease. They may be cough, dyspnea, chills, fever, weight loss, loss of appetite and general malaise
Ocular albinism with late-onset sensorineural deafness (ORPHA:1000)
Ocular albinism with late-onset sensorineural deafness is a rare, X-linked inherited subtype of ocular albinism characterized by severe visual impairment, translucent pale-blue irises, a reduction in the retinal pigment and moderately severe deafness with onset ranging from adolescence to fourth or fifth decade of life.
Ocular anomalies-axonal neuropathy-developmental delay syndrome (ORPHA:496790)
A rare mitochondrial disease characterized by signs and symptoms within a phenotypic and metabolic spectrum that includes global developmental delay, hypotonia, intellectual disability, optic atrophy, axonal neuropathy, hypertrophic cardiomyopathy, lactic acidosis, and increased excretion of Krebs cycle intermediates. Other variable features are spasticity, seizures, ataxia, congenital cataract, and dysmorphic facial features. Age of onset is in the neonatal period or infancy.
Ocular cicatricial pemphigoid (ORPHA:99922)
A rare inflammatory eye disease characterized by sub-epithelial blistering manifesting with bilateral, asymmetrical, chronic or recurrent conjunctivitis and aberrant tissue regeneration leading to progressive conjunctival fibrosis, secondary corneal vascularization and, in some cases, blindness. Patients typically present with conjunctival redness, increased lacrimation, burning and/or foreign body sensation, edema, limbitis and/or varying degrees of ocular pain. Ankyloblepharon may be observed in end stages of the disease.
Ocular cystinosis (ORPHA:411641)
Ocular cystinosis is the benign, adult form of cystinosis (see this term), a metabolic disease characterized by an accumulation of cystine crystals in the cornea and conjunctiva responsible for tearing and photophobia and associated with no other additional manifestations.
Ocular motor apraxia, Cogan type (ORPHA:1125)
Ocular motor apraxia, Cogan type is characterised by impairment of voluntary horizontal eye movements and compensatory head thrust. Around 50 cases have been described so far. The oculomotor manifestations tend to improve with age but the syndrome may also be associated with learning and speech difficulties, or, in some cases, cerebral malformations. Both sporadic and familial forms have been described, with sporadic forms being more frequent. The mode of transmission of the familial form has not yet been clearly established. A gene located on the long arm of chromosome 2, near to the NPHP1 gene involved in nephronophthisis, may be associated with ocular motor apraxia, Cogan type.
Oculo-palato-cerebral syndrome (ORPHA:2714)
Oculopalatocerebral syndrome is characterised by the association of four anomalies: intellectual deficit, microcephaly, palate anomalies and ocular abnormalities.
Epidemiology
It has been described in five patients (three boys and two girls).
Clinical description
Maternal hypertension, oligoamnios and intrauterine growth retardation (IUGR) are often noted during pregnancy. The clinical manifestations are evident from birth. The palate anomaly is usually cleft palate. In the majority of cases, postnatal growth is marked by statural (between -2.5 and -4 SD) and ponderal retardation. Microcephaly is present in all patients (between -2 and -5.6 SD). Persistent hyperplastic primary vitreous (uni- or bilateral) was present in all cases reported so far and may be associated with microphthalmia, cataract or optic atrophy. Facial dysmorphology is characterised by full cheeks, a bulbous nasal tip, and long ears with thickened helices. Hands and feet are small. Anomalies of the external genitalia were reported in some of the male patients, with two of the boys displaying cryptorchidism. Skeletal anomalies include pectus excavatum, joint hyperlaxity and kyphoscoliosis. Intellectual deficit (moderate to severe) is a constant feature and is associated with cerebral atrpohy or quadriplegia in some cases. Hearing difficulties may also be present and a tendency for atopy is often noted.
Etiology
So far, neither a causative gene nor locus has been identified.
Diagnostic methods
Diagnosis is based in the clinical manifestations, in particular on the presence of a persistent hyperplastic primary vitreous in association with other malformations.
Differential diagnosis
Differential diagnosis should include cerebro-oculo-nasal syndrome (see this term) and other syndromes associated with a persistent hyperplastic primary vitreous.
Antenatal diagnosis
Prenatal diagnosis is possible but relies on detection of the malformations and growth retardation by foetal ultrasound.
Genetic counseling
Familial reoccurrence and evidence of consanguinity in two of the three reported families are suggestive of autosomal recessive inheritance. Genetic counselling of families with an affected child should take into account a risk of reoccurrence of 25%.
Management and treatment
Treatment should include surgical correction of the palate anomalies and management of the visual problems. Physical and speech therapy should also be recommended.
Prognosis
Although no data are available on the long-term prognosis, the nature of the anomalies suggests that life expectancy for these patients is normal.

                            Last update: 
                            January 2007


                            - Expert reviewer(s): 
                            Pr Pierre SARDA
Oculoauricular syndrome, Schorderet type (ORPHA:157962)
Oculoauricular syndrome, Schorderet type is a rare, genetic developmental defect during embryogenesis syndrome characterized by various ophthalmic anomalies (including congenital microphthalmia, microcornea, cataract, anterior segment dysgenesis, ocular coloboma and early onset rod-cone dystrophy) and abnormal external ears (low-set pinna with crumpled helix, narrow intertragic incisures, abnormal bridge connecting the crus of the helix and the antihelix, narrow external acoustic meatus, and lobule aplasia).
Oculoauriculofrontonasal syndrome (ORPHA:398156)
A rare dysostosis syndrome characterized by vertical, median craniofacial clefting of fronto-naso-maxillary structures associated with auriculo-mandibular malformations, manifesting with highly variable craniofacial features which include hypertelorism, eyelid colobomas, orbital dystopia, epibulbar dermoids, nasal anomalies (e.g. wide nasal bridge, bifid nose, widely separated, slit-like nares, nasal bone dysplasia), auricular and middle ear dysplasia (microtia, aural stenosis, pre-auricular skin tags/pits), cleft lip/palate, mandibular/maxillary hypoplasia and facial asymmetry. Intracranial abnormalities and extra-craniofacial features are frequently associated.
Oculoauriculovertebral spectrum with radial defects (ORPHA:2549)
A rare branchial arches and limb primordia development disorder characterized by variable degrees of uni- or bilateral craniofacial malformation and radial defects that result in extremely variable phenotypic manifestations. Characteristic features include low postnatal weight, short stature, vertebral defects, hearing loss, and facial dysmorphism (incl. facial asymmetry, external, middle, and inner ear malformations, orofacial clefts, and mandibular hypoplasia). These features are invariably associated with radial defects, such as preaxial polydactyly, thumb and/or radius hypoplasia/agenesis, or triphalangeal thumb. Cardiac, pulmonary, renal, and central nervous system involvement has also been reported.
Oculocerebral hypopigmentation syndrome, Cross type (ORPHA:2719)
Oculocerebral hypopigmentation syndrome, Cross type is a rare congenital syndrome characterized by cutaneous and ocular hypopigmentation, various ocular anomalies (e.g. corneal and lens opacity, spastic ectropium, and/or nystagmus), growth deficiency, intellectual deficit and other progressive neurologic anomalies such as spastic tetraplegia, hyperreflexia, and/or athetoid movements. The clinical picture varies among patients and may also include other anomalies such as urinary tract abnormalities, Dandy-Walker malformations, and/or bilateral inguinal hernia.
Oculocerebral hypopigmentation syndrome, Preus type (ORPHA:2720)
Oculocerebral hypopigmentation syndrome, Preus type is a rare congenital syndrome characterized by skin and hair hypopigmentation, growth retardation, and intellectual deficit that are associated with a combination of various additional clinical anomalies such as ocular albinism, cataract, delayed neuropsychomotor development, sensorineural hearing loss, dolicocephaly, high arched palate, widely spaced teeth, anemia, and/or nystagmus.
Oculocutaneous albinism type 1 (ORPHA:352731)
A form of oculocutaneous albinism (OCA) characterized by a spectrum of hypopigmentation of skin hair and eyes, ranging from little or no pigmentation to localized pigementation. Nystagmus, photophobia and reduced visual acuity are frequently present. The subtypes include OCA1A, OCA1B, type 1 minimal pigment oculocutaneous albinism (OCA1-MP) and type 1 temperature sensitive oculocutaneous albinism (OCA1-TS).
Oculocutaneous albinism type 5 (ORPHA:370091)
A form of oculocutaneous albinism characterized by white skin, golden hair, photophobia, nystagmus, foveal hypoplasia and impaired visual acuity, that affects males and females equally. Patients have been reported only in a consanguineous Pakistani family. The responsible gene has not yet been detected.
Oculocutaneous albinism type 6 (ORPHA:370097)
A form of oculocutaneous albinism characterized by light hair at birth that darkens with age, white skin, transparent irides, photophobia, nystagmus, foveal hypoplasia and reduced visual acuity.
Oculocutaneous albinism type 7 (ORPHA:352745)
A form of oculocutaneous albinism (OCA) characterized by skin and hair hypopigmentation (light blond to dark brown), nystagmus, iris transillumination, visual acuity ranging from 6/9 to 3/60 and hypopigmentation of the peripheral ocular fundus. Photophobia is not a major feature.
Oculocutaneous albinism type 8 (ORPHA:597733)
A type of oculocutaneous albinism characterized by mild hypopigmentation of the skin, hair, and eyes with moderate reduction of visual acuity and nystagmus. The ocular phenotype includes moderate foveal hypoplasia, iris transillumination, and hypopigmentation of the retina.
Oculocutaneous albinism (ORPHA:55)
A group of rare genetic hypopigmentation disorders characterized by a generalized reduction in pigmentation of hair, skin and eyes and variable ocular findings including nystagmus, reduced visual acuity and photophobia. Variants include OCA1A (the most severe form), OCA1B, OCA1-minimal pigment (OCA1-MP), OCA1-temperature sensitive (OCA1-TS), OCA2, OCA3, OCA4, OCA5, OCA6, OCA7 and OCA8.
Oculodental syndrome, Rutherfurd type (ORPHA:2709)
Oculodental syndrome, Rutherfurd type is a rare genetic disorder that is primarily characterized by the classical triad of gingival fibromatosis, non-eruption of tooth and corneal dystrophy (bilateral corneal vascularization and opacity). Abnormally shaped teeth have also been reported. The syndrome is transmitted as an autosomal dominant trait.
Oculoectodermal syndrome (ORPHA:3339)
A rare ectodermal dysplasia characterized by the association of epibulbar dermoids and aplasia cutis congenital.
Oculofaciocardiodental syndrome (ORPHA:2712)
Oculo-facio-cardio-dental syndrome (OFCD) is a very rare multiple congenital anomaly syndrome characterized by dental radiculomegaly, congenital cataract, facial dismorphism and congenital heart disease.
Epidemiology
To date, 20 cases have been reported worldwide.
Clinical description
The most consistent and pathognomic dental finding of OFCD is radiculomegaly (extremely long roots), particularly of the canines and occasionally of other teeth including premolars and incisors. The dental eruption in both the deciduous and the permanent dentition is consistently slow and delayed. Oligodontia, fused teeth, supernumerary teeth, malformed permanent teeth, enamel defects, root dilacerations, malposition and malocclusion, have also been reported. Ocular abnormalities include bilateral congenital cataracts, microphthalmia, regressive vision impairment, secondary glaucoma, and ptosis. Exotropia is very common. The facial features described include a long narrow face, high nasal bridge, broad nasal tip with separated nasal cartilages, laterally curved and thick eyebrows, long philtrum, clefts of the hard/soft palate. Cardiac defects reported include ventricular septal defect, atrial septal defect, mild cardiomegaly, ventricular and atrial hypertrophy, benign peripheral pulmonic stenosis, mitral valve prolapse. Occasional reports have noted skeletal findings (syndactly of the second and third toes, hammer-type flexion of the second and fourth toes, radio-ulnar synostosis, and vertebral and rib anomalies), intestinal malrotation, hearing impairment, intellectual and psychomotor deficit.
Etiology
The BCOR gene on chromosome Xp11.4 is causative, however its exact function remains unknown.
Diagnostic methods
Diagnosis of OFCD is hard for medical specialists and the syndrome is often unrecognized. The specific dental findings (visible on a panoramic radiograph of the jaws) can be easily diagnosed by an orthodontist or a dentist.
Genetic counseling
OFCD is an X-linked dominant syndrome that is lethal in males.
Management and treatment
Management requires appropriate cardiac, ophthalmic and dental care.

                            Last update: 
                            November 2007


                            - Expert reviewer(s): 
                            Pr Agnès BLOCH-ZUPAN
Oculogastrointestinal muscular dystrophy (ORPHA:1876)
Oculogastrointestinal muscular dystrophy is an extremely rare autosomal recessively inherited neuromuscular disease characterized by ocular manifestations such as ptosis and diplopia followed by chronic diarrhea, malnutrion and intestinal peudo-obstruction.
Oculomaxillofacial dysostosis (ORPHA:1794)
Oculomaxillofacial dysostosis is a rare, genetic bone developmental disorder characterized by short stature, orbital region and ocular abnormalities (e.g. asymmetric orbits, anophthalmia, down-slanted and S-shaped palpebral fissures, sparse eyebrows/eyelashes, abnormal eyelids, ectropion, symblepharon, corneal leukoma), abnormal nose (e.g. broad and abnormally modeled nasal root, bridge and tip, lateral deviation), malar hypoplasia, cleft lip/palate, and oblique facial clefts. Intellectual disability, microcephaly, micrognathia and limb anomalies (e.g. hemimelia, abnormal scapular girdle, brachydactyly, syndactyly, broad halluces) have also been reported.