TaoMedAI/RareMedData huggingface dataset:
Otopalatodigital syndrome type 1 (ORPHA:90650)
A disorder that is the mildest form of otopalatodigital syndrome spectrum disorder, and is characterized by a generalized skeletal dysplasia, mild intellectual disability, conductive hearing loss, and typical facial anomalies.
Epidemiology
To date, more than 100 cases have been described in the world literature.
Clinical description
OPD1 is a congenital disorder characterized by generalized skeletal dysplasia which include camptodactyly, long spatulate fingers, short first digits (''tree frog'' hands and feet), pectus carinatum, mild campomelia, mild femoral bowing, limitation of joint movement (elbow extension, wrist abduction) and malformed auditory ossicles leading to conductive hearing loss in some individuals. Additional features include typical craniofacial anomalies (occipital prominence, frontal bossing with prominent supraorbital ridges, flat nasal bridge, hypertelorism, microstomia, dental abnormalities, and cleft palate (pugilistic face)). In affected females, a similar but usually milder spectrum of expressivity is observed.
Etiology
OPD1 is caused by gain of function mutations in the gene FLNA (Xq28) that encodes filamin A. However the pathogenesis of OPD1 is still elusive. OPD1 is allelic with 4 other skeletal dysplasias (OPD2, Melnick-Needles syndrome (MNS), terminal osseous dysplasia - pigmentary defects (TOD) and frontometaphyseal dysplasia (FMD)).
Genetic counseling
OPD1 is inherited in an X-linked dominant manner. Male-to-male transmission has not been reported. The risk of transmitting the mutation in each pregnancy is 50%; males inheriting the mutation will be affected while females who inherit the mutation have a broad range of phenotypic expression.

                            Last update: 
                            May 2015


                            - Expert reviewer(s): 
                            Pr Stephen ROBERTSON
Otopalatodigital syndrome type 2 (ORPHA:90652)
A severe form of otopalatodigital syndrome spectrum disorder, and is characterized by dysmorphic facies, severe skeletal dysplasia affecting the axial and appendicular skeleton, extraskeletal anomalies (including malformations of the brain, heart, genitourinary system, and intestine) and poor survival.
Epidemiology
To date, more than 40 cases of Otopalatodigital syndrome type 2 (OPD2) have been described in the literature.
Clinical description
OPD2 is a congenital disorder. Intrauterine growth is usually normal and affected infants have large anterior fontanels, and facial dysmorphism including broad forehead and lateral fullness of the supraorbital ridge, hypertelorism, downslanting palpebral fissures, stubby nose with a flat root, midfacial hypoplasia, microstomia (with typical down turned bow of the upper lip), micrognathia, Pierre Robin sequence, posterior cleft palate (submucosal cleft palate or cleft velum), glossoptosis, malformed and/or apparently low-set ears. Additional features include skeletal anomalies: pectus deformity, short limbs, campomelia, fibular agenesis, flexion contractures of elbows, knees, rocker bottom or equinovarus feet, syndactyly (usually involving fingers III and IV in the hands and toes II to V in the feet), camptodactyly of fingers, and absent halluces. Extraskeletal malformations include malformations of the central nervous system (myelomeningocele /encephalocele, cerebellar hypoplasia, hydrocephalus), heart (congenital valvular heart defects), intestine, genitourinary system (hydronephrosis ± urethral valve/reflux, hypospadias, epispadias). Congenital corneal opacities, bilobed tongue, deafness, and Dandy-Walker malformation have been reported in a minority of OPD2 cases. Congenital glaucoma and cataracts have been described in one patient. Psychomotor development varies from normal to mild intellectual disability. Carrier females with OPD2 can be asymptomatic or exhibit a phenotype that can extend from a mild subclinical osteodysplasia to a presentation indistinguishable from that of affected males. Prognosis of OPD2 is poor and perinatal death is common, secondary to cardio respiratory failure.
Etiology
OPD2 is caused by gain of function mutations in the gene FLNA (Xq28) that encodes filamin A. However the pathogenesis is still elusive. OPD2 is allelic with 4 other skeletal dysplasias (OPD1, Melnick-Needles syndrome (MNS), terminal osseous dysplasia - pigmentary defects (TOD) and frontometaphyseal dysplasia (FMD)).
Genetic counseling
OPD2 is inherited in an X-linked dominant manner. Male-to-male transmission has not been reported. The risk of transmitting the mutation in each pregnancy is 50%; males inheriting the mutation will be affected while females who inherit the mutation are less severely affected.

                            Last update: 
                            May 2015


                            - Expert reviewer(s): 
                            Pr Stephen ROBERTSON
Otospondylomegaepiphyseal dysplasia (ORPHA:1427)
Otospondylomegaepiphyseal dysplasia (OSMED) is an inborn error of cartilage collagen formation characterized by sensorineural hearing loss, enlarged epiphyses, skeletal dysplasia with disproportionately short limbs, vertebral body anomalies and a characteristic facies.
Epidemiology
The prevalence is unknown but less than 30 cases have been described in the literature so far.
Clinical description
Typical facial features include midface hypoplasia, a short nose with anteverted nares and a flat nasal bridge, a long philtrum, cleft palate/bifid uvula, micrognathia, and hypertelorism. Joint pain and restricted mobility of the metacarpophalangeal joints appear during the second decade of life. The sensorineural hearing loss is generally described as moderate and nonprogressive. Early onset of osteoarthritis has also been reported.
Etiology
OSMED is classed among the type XI collagenopathies as the majority of reported cases have been associated with homozygous mutations in the COL11A2 gene (6p21.3), encoding the alpha2 chain of type XI collagen.
Diagnostic methods
Diagnosis is made on the basis of the clinical phenotype and typical radiographic findings: shortening of the long bones (humerus, radius, ulna, tibia, and fibula) with large epiphyses and metaphyseal flaring, coronal clefting and mild to moderate platyspondyly.
Differential diagnosis
OSMED shows significant clinical overlap with Weissenbacher-Zweymuller syndrome (WZS) and Stickler syndrome (see these terms). Whilst OSMED and Stickler syndrome can be distinguished early in life due to the absence of ocular anomalies in OSMED, differentiation of OSMED and WZS (also associated with heterozygous mutations in the COL11A2 gene) may be more problematic.
Genetic counseling
OSMED is inherited as an autosomal recessive trait.
Management and treatment
Treatment is symptomatic only, involving closure of the cleft palate, audiometry and adapted management of the hearing loss, and treatment of the joint pain.
Prognosis
The prognosis depends on the severity of the osteoarthritis (which may require early joint replacement), hearing loss and joint pain.

                            Last update: 
                            November 2008


                            - Expert reviewer(s): 
                            Dr Martine LE MERRER
Ovarian dysgerminoma (ORPHA:99912)
A rare malignant germ cell tumor of ovary characterized by a solid, lobulated mass, usually with a diameter of more than 10 cm, generally occurring in children or young women who present with abdominal pain or an abdominal mass and elevated serum LDH. It is bilateral in about 20% of cases, although the contralateral tumor may not be evident on macroscopic examination. Histopathologically, tumor cells are uniform rounded primitive germ cells with clear cytoplasm and macronucleoli, arranged in nests or cords separated by thin fibrous septa containing lymphocytes. Immunohistochemistry should be positive for OCT4 or SALL4, KIT (CD117), and/or D2-40.
Ovarian fibroma (ORPHA:314473)
A rare benign ovarian tumor of sex cord / stromal origin characterized by an abdominal mass which may present with abdominal pain, distension, or menorrhagia, among others, or may also be asymptomatic. Association with ascites and hydrothorax is known as Meigs syndrome. The tumor can be solid and/or cystic in nature. Histologically it features bundles of spindle cells forming variable amounts of collagen, without cellular atypia or atypical mitoses.
Ovarian fibrothecoma (ORPHA:314478)
Ovarian fibrothecoma is a rare, benign, sex cord-stromal neoplasm, with a typically unilateral location in the ovary, characterized by mixed features of both fibroma and thecoma. Patients may be asymptomatic or may present with pelvic/abdominal pain and/or distension and, occasionally, with post-menopausal bleeding. Large tumors (>10cm) are often associated with pleural effusion and ascites (the Meigs syndrome triad).
Ovarian hyperstimulation syndrome (ORPHA:64739)
A rare non-malformative gynecological disease affecting pre-menopausal women usually following treatment with ovarian stimulating hormones, characterized by ovarian enlargement and, to varying degrees, shift of serum from the intravascular space to the third space, mainly into the peritoneal, pleural, and to a lesser extent to the pericardial cavities. Presenting symptoms include abdomen distention, pain, nausea, and vomiting. Severity ranges from mild to life-threatening and is complicated by increased risk of thrombosis, acute hepato-renal failure, acute respiratory distress syndrome, and ovarian torsion and rupture.
Overgrowth syndrome with 2q37 translocation (ORPHA:498488)
A rare overgrowth syndrome with skeletal involvement characterized by long and slim body habitus and multiple skeletal manifestations, such as scoliosis, macrodactyly of the big toes, arachnodactyly of fingers and toes, camptodactyly and clinodactyly, and progressive valgus deformities of the feet. Epimetaphyseal dysplasia, bowing of the tibiae, and dysmorphic facial features (hypertelorism, high palate, or micrognathia), as well as aortic root dilatation and umbilical hernia have also been reported.
Overgrowth-macrocephaly-facial dysmorphism syndrome (ORPHA:137634)
A rare overgrowth syndrome characterized by tall stature, learning difficulties and facial dysmorphism.
Overgrowth-metaphyseal undermodeling-spondylar dysplasia syndrome (ORPHA:498485)
A rare overgrowth syndrome with skeletal involvement characterized by pre- or postnatal onset of overgrowth, accelerated bone age in infancy and early childhood, tall stature, bony overgrowth of the skull base, spondylar dysplasia, and undermodeling of the tubular bones. Facial dysmorphism includes mild hypertelorism, depressed nasal bridge, short and broad nose, and full lower lip. Additional reported features are scoliosis, as well as delayed puberty, cryptorchidism, and hypospadias.
Overhydrated hereditary stomatocytosis (ORPHA:3203)
Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia.
Epidemiology
OHSt is very rare with only seven cases described in the literature so far.
Clinical description
Onset occurs during the neonatal period or infancy with hemolytic anemia that may require occasional blood transfusions. Splenomegaly or hepatosplenomegaly are present. The disease course is marked by the usual complications of hemolytic anemia (biliary lithiasis) and, remarkably, by a strong tendency for iron overload.
Etiology
In the majority of cases, OHSt is caused by mutations in the RHAG gene (6p21-qter) encoding the Rh-associated glycoprotein component of the Rh complex.
Diagnostic methods
Diagnosis is based on a massive right shift of the osmotic gradient ektacytometry curve indicating overhydrated red cells and decreased osmotic resistance, together with a substantial increase in the monovalent cation leak compared to controls, and a sharp decrease of the leak as a function of decreasing temperature. Blood smears show an elevated percentage of well formed stomatocytes. There is macrocytosis, a low mean cell hemoglobin concentration (MCHC) and a high reticulocyte count. Electrophoresis reveals that the membrane protein stomatin is absent or present at only low levels.
Differential diagnosis
The differential diagnosis should include the most common form of hereditary stomatocytosis, dehydrated hereditary stomatocytosis, as well as hereditary cryohydrocytosis with reduced stomatin (see these terms).
Genetic counseling
OHSt is transmitted as an autosomal dominant trait but de novo mutations are quite common.
Management and treatment
Treatment involves blood transfusions, when necessary, together with management of biliary lithiasis and iron overload. Splenectomy is contraindicated in OHSt patients as it may induce venous thromboembolic complications.
Prognosis
With correct management of the complications, the prognosis is good.

                            Last update: 
                            October 2008


                            - Expert reviewer(s): 
                            Pr Jean DELAUNAY
Overlap myositis (ORPHA:206572)
A rare idiopathic inflammatory myopathy (IIM) with a heterogeneous phenotype characterized by myositis with at least one clinical and/or autoantibody overlap feature. Possible clinical overlap features include polyarthritis, Raynaud's phenomenon, sclerodactyly, scleroderma (proximal to metacarpophalangeal joints), lung interstitial pneumonia, and/or clinical signs of systemic lupus erythematosus (SLE).
Epidemiology
Prevalence and annual incidence are not known. Estimates are difficult to determine because of low recognition levels of this form of IIM. The disorder is more common in adult women and is frequently associated with other connective tissue disorders such as systemic sclerosis, SLE, rheumatoid arthritis, and Sjögren syndrome.
Clinical description
Overlap myositis (OM) is a clinically heterogeneous, poorly recognized subtype of idiopathic inflammatory myopathy. Patients with myositis and one clinical and/or autoantibody overlap feature are considered to have OM. Possible clinical overlap features include polyarthritis, Raynaud's phenomenon, sclerodactyly, scleroderma (proximal to metacarpalphalangeal joints), lung interstitial pneumonia, and/or clinical signs of systemic lupus erythematosus (SLE). Overlap autoantibodies include those observed with scleroderma (such as anti-Ku or anti-PMScl), mixed connective tissue disease (MCTD; with anti-RNP), SLE (frequent ANA positivity), and/or some inflammatory myopathies such as anti-synthetase syndrome (anti-JO1).
Etiology
OM covers a range of inflammatory myopathies and other connective tissue diseases for which the etiology is generally poorly understood.
Diagnostic methods
The precise diagnostic criteria are still debated. Sometimes OM is defined as the combination of myositis and another connective tissue disorder (systemic sclerosis, SLE, RA, Sjögren syndrome, etc.). Sometimes, OM is defined as a myositis with overlap features without fulfilling criteria of another connective tissue disorder. The diagnosis of this disorder improves with the increased screening for myositis-specific and myositis-associated autoantibodies. Some antibodies may delineate homogeneous subgroup of myositis patients, such as anti-RNP with specific extramuscular manifestations (puffy hands / Raynaud's phenomenon, arthralgia / ILD).
Differential diagnosis
The differential diagnoses include other IIM disorders (dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy and inclusion body myositis). There is still debate about OM as a distinct entity as opposed to a specific CTD with muscle involvement.
Management and treatment
There is no specific recommendation for therapeutic management. The treatment is usually based on the use of corticosteroids and/or other immunosuppressants.
Prognosis
Due to the heterogeneity of the diagnostic criteria and the small number of patients in the published studies, the specific prognosis of OM is not well known.

                            Last update: 
                            March 2021


                            - Expert reviewer(s): 
                            Dr Céline ANQUETIL  - Pr Olivier BENVENISTE
Oxoglutaric aciduria (ORPHA:31)
A rare, genetic, inborn error of metabolism disorder characterized by neonatal-onset of developmental delay, hypotonia, hepatomegaly, lactic acidemia, increased creatine kinase levels, elevated alpha-ketoglutaric acid in urine, and a decreased plasma beta-hydroxybutyrate-to-acetoacetate ratio. Pyruvate dehydrogenase deficiency can be associated, leading to hypoglycemia and neurologic anomalies, including seizures.
Pachydermoperiostosis (ORPHA:2796)
Pachydermoperiostosis (PDP) is a form of primary hypertrophic osteoarthropathy (see this term), a rare hereditary disorder, and is characterized by digital clubbing, pachydermia and subperiosteal new bone formation associated with pain, polyarthritis, cutis verticis gyrata, seborrhea and hyperhidrosis. Three forms have been described: a complete form with pachydermia and periostitis, an incomplete form with evidence of bone abnormalities but lacking pachydermia, and a forme frusta with prominent pachydermia and minimal-to-absent skeletal changes.
Epidemiology
The prevalence is unknown. PDP occurs predominantly in men (male to female ratio: 7:1) and the disease is more severe in men than in women.
Clinical description
PDP typically begins during childhood or adolescence and may stabilize after 5-20 years of progression, or progress constantly. However, in the neonatal period, late closure of the fontanels and a patent arterial duct (see this term) may be observed. PDP presents with digital clubbing and dermatological (pachydermia, thickening and furrowing of the facial features, cutis verticis gyrata, seborrhea, edema, hyperhidrosis) and rheumatological symptoms (joint effusion, arthritis, acro-osteolysis, periosteal ossification). Patients may develop severe kyphosis, restricted motion and neurological manifestations. PDP may also be associated with congenital heart disease, particularly patent arterial duct.
Etiology
Mutations in the HPGD gene (4q33-q34) have been identified. The gene encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the main enzyme of prostaglandin degradation. Patients with homozygous mutations have chronically elevated prostaglandin E2 levels.
Diagnostic methods
Diagnosis is based on clinical signs, X-ray exam, magnetic resonance imaging (MRI) and/or radionucleotide bone imaging showing typical bone abnormalities, such as diaphyseal periostosis and acro-osteolysis.
Differential diagnosis
Differential diagnoses include cranio-osteoarthropathy (see this term), secondary hypertrophic osteoarthropathy, chronic recurrent multifocal osteomyelitis, SAPHO and Camurati-Engelman disease (see these terms), thyroid acropachy and syphilitic periostosis.
Genetic counseling
PDP is inherited as an autosomal recessive trait; however, heterozygous carriers can have a mild phenotype. Genetic counseling should be offered to patients and their families.
Management and treatment
Rheumatologic symptoms can be improved by nonsteroidal anti-inflammatory drugs, corticosteroids or colchicine. Clinical improvement of the dermatological symptoms is achieved by retinoids. Plastic surgery may be helpful for facial involvement. Surgical reduction of finger clubbing has been performed with success.
Prognosis
PDP may progress constantly, leaving patients with chronic debilitating complications, such as clubbing and arthritis.

                            Last update: 
                            January 2011


                            - Expert reviewer(s): 
                            Pr Hermann GIRSCHICK
Pachygyria-intellectual disability-epilepsy syndrome (ORPHA:2798)
A rare, genetic neurological disorder characterized by the presence of diffuse pachygyria and arachnoid cysts, psychomotor developmental delay and intellectual disability. Seizures (absence, atonic and generalized tonic-clonic) and, on occasion, headache are also associated.
Paget disease of the nipple (ORPHA:180275)
Paget disease of the nipple describes a rare presentation of breast cancer, seen most frequently in women aged 50-60, manifesting with nipple drainage and itching, erythema, crusty and excoriated nipple, thickened plaques, and hyperpigmentation (less frequently). It is due to tumor cells invading the nipple-areola complex and represents 1-3% of all new breast cancer diagnoses.
PAGOD syndrome (ORPHA:991)
PAGOD syndrome is a severe developmental syndrome characterized by multiple congenital anomalies including cardiovascular defects, pulmonary hypoplasia, diaphragmatic defects and genital anomalies.
Epidemiology
Since the first publication in 1991, only 11 patients have been described.
Clinical description
Neonates with PAGOD syndrome present with several visceral anomalies: hypoplasia of right or left lung, diaphragmatic hernia, omphalocele, various cardiac anomalies including, amongst others, atrial septal defect, left ventricular hypoplasia or ventricular septal defect, and great vessels anomalies such as aortic hypoplasia and pulmonary artery hypoplasia or atresia. Cardiac and mediastinal structures may be in dextroposition. Ambiguous external genitalia can be observed in some cases and all patients present gonadal agenesis or hypoplasia and developmental anomalies of Wolffian and Mullerian duct structures.
Etiology
Etiology is unknown but vitamin A deficiency has been suggested to play a role in the development of the syndrome.
Genetic counseling
Almost all cases are sporadic, except for 2 siblings, suggesting autosomal recessive inheritance.
Prognosis
Life expectancy is reduced due to cardiac and respiratory complications.

                            Last update: 
                            December 2011
Painful orbital and systemic neurofibromas-marfanoid habitus syndrome (ORPHA:300501)
Painful orbital and systemic neurofibromas-marfanoid habitus syndrome is a rare, benign, peripheral nerve sheath tumor disorder characterized by multiple, painful, mucin-rich plexiform neurofibromas located in the orbits, cranium, large spinal nerves and mucosa, associated with a marfanoid habitus, enlarged corneal nerves, congenital neuronal migration anomalies and facial dysmorphism which includes ptosis, proptosis, prominent nose, full lips, gingival hyperplasia, and multiple subcutaneous and submucosal nodules in the lips and sublingual zone.
Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome (ORPHA:477993)
Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, axial hypotonia, palate abnormalities (including cleft palate and/or high and narrow palate), dysmorphic facial features (including prominent forehead, hypertelorism, downslanting palpebral fissures, wide nasal bridge, thin lips and widely spaced teeth), and short stature. Additional manifestations may include digital anomalies (such as brachydactyly, clinodactyly, and hypoplastic toenails), a single palmar crease, lower limb hypertonia, joint hypermobility, as well as ocular and urogenital anomalies.
Palmoplantar keratoderma, Nagashima type (ORPHA:140966)
A rare autosomal recessive, isolated diffuse palmoplantar keratoderma charactized by transgressive and nonprogressive palmoplantar keratoderma resembling a mild form of mal de Meleda.