TaoMedAI/RareMedData huggingface dataset:
Osteogenesis imperfecta type 2 (ORPHA:216804)
A lethal type of osteogenesis imperfecta (OI) characterized by increased bone fragility, low bone mass and susceptibility to bone fractures and presenting with multiple rib and long bone fractures at birth, marked deformities, broad long bones, low density skull on X-ray, and dark sclera.
Epidemiology
The overall prevalence of OI is estimated at between 1/10,000 and 1/20,000 but the prevalence of type II is unknown.
Clinical description
There are three subtypes of OI type II (A, B and C) that are characterized by different radiological features. Patients with OI type IIA present with broad ribs with multiple fractures, continuous beaded ribs and severe under-modeling of the femur. OI type IIB presents with normal or thin ribs with some fractures, discontinuous beaded ribs and some under-modeling of the femur. OI type IIC presents with varying thickness of the ribs, discontinuous beading of the ribs, malformed scapulae and ischiae, and long bones with thin shafts and expanded metaphyses. Type IIC is extremely rare and its existence is even doubted.
Etiology
Variants in the COL1A1 and COL1A2 genes (17q21.31-q22 and 7q22.1 respectively) cause OI type IIA and IIB, and transmission is autosomal dominant. Type IIB can also be autosomal recessive, caused by mutations in the CRTAP gene (3p22; sometimes described as OI type VII) or the P3H1 gene (1p34; sometimes described as OI type VIII) or the PPIB gene (15q21-q22; sometimes described as OI type IX). OI type IIC appearances have been reported in fetuses with mutations in the MESD gene (15q25).
Diagnostic methods
Diagnosis is typically prenatal due to suspicious ultrasound findings.
Differential diagnosis
Differential diagnosis includes thanatophoric dwarfism, severe hypophosphatasia, and mucolipidosis type II.
Antenatal diagnosis
Prenatal diagnosis of type II OI may be suggested by fetal ultrasound appearances, and confirmed by genetic testing of amniocytes.
Genetic counseling
The disease is either autosomal dominant or autosomal recessive depending on the gene involved. Autosomal dominant cases occur either sporadically or due to germline mosaicism. The appropriate genetic counseling should be offered to affected families.
Management and treatment
Management is initially expectant; some infants with apparently very severe changes on ultrasound may nevertheless survive with intensive support and early institution of bone-directed therapy such as bisphosphonates.
Prognosis
The majority of those identified of having type II changes antenatally will die either before birth or in the perinatal period. A few may survive with continued intensive treatment.

                            Last update: 
                            May 2021


                            - Expert reviewer(s): 
                            Pr Nick BISHOP
Osteogenesis imperfecta type 3 (ORPHA:216812)
A severe type form osteogenesis imperfecta characterized by increased bone fragility and low bone mass clinically manifesting as susceptibility to bone fractures, severe short stature, a triangular face, moderate to severe scoliosis, blue or blue-grey sclera, and dentinogenesis imperfecta.
Osteogenesis imperfecta type 4 (ORPHA:216820)
A moderately severe form of osteogenesis imperfecta characterized by increased bone fragility and low bone mass that clinically manifests from infancy as susceptibility to bone fractures, short stature, mild to moderate scoliosis in most, gray-blue or white sclera, and dentinogenesis imperfecta.
Osteogenesis imperfecta type 5 (ORPHA:216828)
A moderate form of osteogenesis imperfecta characterized by increased bone fragility and low bone mass that clinically manifests with susceptibility to bone fractures of variable severity, metaphyseal changes at birth, short stature, dislocation of the radial head, mineralized interosseous membranes, hyperplasic callus (occurring more often during periods of more rapid growth), white sclera and absence of dentinogenesis imperfecta.
Osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome (ORPHA:2773)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, osteogenesis imperfecta, presence of wormian bones, seizures, ocular abnormalities (blue sclerae, optic atrophy, retinal detachment), and dysmorphic facial features (including frontal bossing, low anterior hairline, medial flare of the eyebrows, long eyelashes, hypertelorism, depressed nasal bridge, and low-set, large ears). There have been no further descriptions in the literature since 1994.
Osteoglosphonic dysplasia (ORPHA:2645)
A rare disorder characterized by dwarfism, severe craniofacial abnormalities and multiple unerupted teeth.
Epidemiology
Less than ten cases have been reported so far.
Clinical description
Main clinical features include craniosynostosis, acrocephaly, a prominent forehead, depressed nasal bridge, hypertelorism, midface hypoplasia, macroglossia, unerupted teeth, short neck, short and bowed limbs, short and broad hands and fingers, and flat feet. The main radiographic features are craniostenosis, fibrous dysplasia, metaphyseal lucencies and platyspondyly. Intelligence is usually normal.
Etiology
Osteoglosphonic dysplasia (OGD) is caused by mutations in the FGFR1 gene (8p11.2-p11.1).
Genetic counseling
OGD is transmitted in an autosomal dominant manner.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Dr Martine LE MERRER
Osteomesopyknosis (ORPHA:2777)
Osteomesopyknosis is a very rare benign bone disorder characterized by bone dysplasia manifested by patchy sclerosis of the axial skeleton and increased bone mineral content.
Epidemiology
The prevalence and incidence of this disorder are not known. It has been reported in fewer than 5 families, primarily in France.
Clinical description
Osteomesopyknosis may be underdiagnosed due to confusion with autosomal dominant osteopetrosis (Albers-Schönberg osteopetrosis, see this term). The condition is usually found incidentally on radiological examination and is very mild, sometimes accompanied by pain. Increased density of the vertebral plates, pelvis and occasionally of the upper femur have been reported, as well as kyphoscoliosis and femoral cysts.
Etiology
The genetic basis underlying the disorder is not known.
Genetic counseling
The disorder appears to follow an autosomal dominant pattern of inheritance.

                            Last update: 
                            June 2012
Osteonecrosis of the jaw (ORPHA:399293)
A rare osteonecrosis characterized by an exposed necrotic lesion in the mandible or maxilla present for more than eight weeks, arising as a complication of antiresorptive medication, dental interventions, or trauma and infections. Patients may present with pain, altered neurosensory functions, secondary infections, and (in advanced stages) pathological fractures, or fistulae.
Osteopathia striata-cranial sclerosis syndrome (ORPHA:2780)
Osteopathia striata with cranial sclerosis (OS-CS) is a bone dysplasia characterized by longitudinal striations of the metaphyses of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss.
Epidemiology
Fewer than 100 cases have been reported in the literature.
Clinical description
The clinical presentation is highly variable even within the same family, ranging from mild skeletal manifestations to multisystem organ involvement. Cardiac malformations (ventricular septal defect, aortic stenosis), developmental delay, cranial nerve palsies, anal malformations, cataracts and nervous system malformations are frequent. Vertebral anomalies (scoliosis, spondylolisthesis), anomalies of extremities (clubfoot, unusually long and thin fingers with clinodactyly of distal phalanges), hypertelorism, frontal bossing, broad nasal bridge, prominent occipital bony protrusion and mild intellectual impairment have also been documented. In rare cases, OS-CS has been reported in association with Hirschsprung disease, Pierre Robin sequence, coronal craniostenosis, hydrocephalus and laryngotracheomalacia (see these terms).
Etiology
OS-CS is associated with mutations in the Wilms tumour gene on the X chromosome (WTX), a repressor of WNT signaling (beta-catenin pathway implicated in control of target genes in the nucleus).
Diagnostic methods
Diagnosis is based on clinical and radiological examination, which reveals cranial sclerosis, longitudinal striations in the widened metaphyses of the long bones, and sclerosis of the ribs. Genetic testing is available to confirm the diagnosis.
Differential diagnosis
Differential diagnosis includes a large number of conditions with primary or secondary bone sclerosis. As the macrocephaly seems to be an early and constant clinical feature, OS-CS should be considered in the differential diagnosis of fetuses/infants with unexplained macrocephaly.
Antenatal diagnosis
In the most severe cases, the disorder can be diagnosed prenatally by detection of increased biparietal diameter of the fetal head on ultrasound examination. Prenatal genetic diagnosis is available if the disease-causing mutation in the family is known.
Genetic counseling
OS-CS follows an X-linked dominant pattern of inheritance, with frequent lethality in males.
Management and treatment
Management is supportive and aims at providing multidisciplinary surveillance and symptomatic management of complications.
Prognosis
Cases with severe multiple manifestations and those associated with Hirschsprung disease, Pierre Robin sequence and coronal craniostenosis have poor prognosis.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Dr Ravi SAVARIRAYAN  - Dr Zornitza STARK
Osteopathia striata-pigmentary dermopathy-white forelock syndrome (ORPHA:2779)
A rare primary bone dysplasia characterized by the association of osteopathia striata (longitudinal striations through most of the long bones) with a macular, hyperpigmented dermopathy and a white forelock.
Osteopenia-intellectual disability-sparse hair syndrome (ORPHA:2324)
A rare syndrome characterized by sparse hair, osteopenia, intellectual disability, minor facial abnormalities, joint laxity and hypotonia. There have been no further descriptions in the literature since 1992.
Osteopetrosis with renal tubular acidosis (ORPHA:2785)
Osteopetrosis with renal tubular acidosis is a rare disorder characterized by osteopetrosis (see this term), renal tubular acidosis (RTA), and neurological disorders related to cerebral calcifications.
Epidemiology
Prevalence of this disorder is not known. Fewer than 100 cases have been reported to date. Many reports involved families of North African and Middle Eastern descent, but cases have been documented worldwide.
Clinical description
Patients present a triad of mild osteopetrosis, mixed proximal and distal RTA, and intracerebral calcifications. Other clinical manifestations include fractures, growth failure and short stature, developmental delay, intellectual deficit, dental malocclusions/malalignment, cranial nerve compression and hearing impairment.
Etiology
Osteopetrosis with renal tubular acidosis is caused by mutations in the CA2 gene (8q22) encoding carbonic anhydrase II.
Diagnostic methods
Diagnosis is based on radiological findings in the presence of acidosis and intracerebral calcifications, and can be confirmed by molecular genetic testing.
Antenatal diagnosis
Antenatal diagnosis is possible if the mutation(s) causing the condition in the family are known.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Treatment is symptomatic. Referral to a renal physician to manage the acidosis is recommended.
Prognosis
Severity is variable but the disorder has a milder course than in patients with classic osteopetrosis.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Dr Ravi SAVARIRAYAN  - Dr Zornitza STARK
Osteopetrosis-hypogammaglobulinemia syndrome (ORPHA:178389)
Osteopetrosis-hypogammaglobulinemia syndrome is an extremely rare primary bone dysplasia with increased bone density disorder characterized by severe osteoclast-poor osteopetrosis associated with hypogammaglobulinemia. Patients typically present infantile malignant osteopetrosis (manifesting with increased bone density, bone fractures, abnormal eye movements/visual loss, nystagmus), hematologic abnormalities with bone marrow failure (e.g. anemia, hepatosplenomegaly) and immunological deficiency (manifesting as recurrent respiratory infections) associated with reduced immunoglobulin levels due to impaired peripheral B cell differentiation.
Osteoporosis-oculocutaneous hypopigmentation syndrome (ORPHA:2786)
A rare genetic disease characterized by congenital oculocutaneous hypopigmentation, visual impairment, generalized osteoporosis with skeletal anomalies such as short stature, short neck and trunk, kyphosis, scoliosis, and platyspondyly, and dysmorphic facial features (including long philtrum, small mouth, micrognathia, and prominent ears). Moderate joint hyperelasticity and muscular hypotrophy have also been reported.
Osteoradionecrosis of the mandible (ORPHA:521127)
A rare radiation-induced disorder characterized by exposed irradiated bone that fails to heal over a period of three months without evidence of persisting or recurrent tumor. Patients present with pain, dysesthesia, dysgeusia, fetor oris, trismus, ulceration or necrosis of the mucosa with exposure of necrotic bone, and local suppuration. Complications include pathological fractures, formation of intra- or extra-oral fistulae, and infection. MRI shows cortical destruction, abnormal bone marrow signal, and irregular contrast enhancement.
Osteosarcoma (ORPHA:668)
Osteosarcoma is a primary malignant tumour of the skeleton characterised by the direct formation of immature bone or osteoid tissue by the tumour cells.
Epidemiology
Classic osteosarcoma is a rare (0.2% of all malignant tumours) highly malignant tumour, with an estimated incidence of 3 cases/million population/year.
Clinical description
Osteosarcoma arises predominantly in the long bones and rarely in the soft tissues. The age at presentation ranges from 10 to 25 years of age.
Diagnostic methods
Plain radiographs, computed tomography, magnetic resonance imaging, angiography and dynamic bone scintigraphy are used for diagnosis, evaluation the extent of tumour involvement and for making decisions about the type of operation and, if necessary, the type of reconstruction required.
Management and treatment
In the past, all patients with osteosarcoma were treated by amputation but the cure rate was under 10% and almost all patients died within a year from diagnosis. At present, the percentage of patients cured varies between 60% and 70% for localised osteosarcoma at onset (80% of cases) treated in specialised bone tumour centres with pre- and postoperative chemotherapy associated with surgery. Surgery is conservative (limb salvage) in more than 90% of patients.
Prognosis
Prognosis is more severe (cure rate about 30%) for tumours located in the axial skeleton and in patients with metastasis at onset.

                            Last update: 
                            January 2007


                            - Expert reviewer(s): 
                            Dr Piero PICCI
Osteosclerosis-developmental delay-craniosynostosis syndrome (ORPHA:178377)
This newly described syndrome is characterized by osteosclerosis, developmental delay and craniosynostosis (see this term).
Epidemiology
It has been reported in 13 patients from a four-generation family.
Clinical description
Osteosclerosis was constant and most pronounced in the cranial base and calvarium. Craniosynostosis was reported in four patients and a mild developmental delay in three patients. Dysmorphic features were constant and included macrocephaly, brachycephaly, wide and high forehead, hypertelorism, prominent cheekbones and prominent jaw.
Etiology
A missense mutation A214T in the low-density lipoprotein receptor related protein 5 gene, LRP5, was found in all analyzed affected individuals. In this family, findings are consistent with autosomal dominant inheritance.

                            Last update: 
                            November 2010
Osteosclerosis-ichthyosis-premature ovarian failure syndrome (ORPHA:75325)
A rare genetic disease characterized by sclerosing dysplasia affecting the diaphyseal and metaphyseal regions of the long bones, as well as the skull and metacarpals, in association with skin changes like those seen in ichthyosis vulgaris and premature ovarian failure with bilateral hypoplasia of the ovaries. Patients present in adulthood, primarily with swelling of the extremities and occasional mild pain in the legs.
Osteosclerotic bone dysplasia (ORPHA:1832)
A rare disorder defined by generalized osteosclerosis with periosteal bone formation, characteristic facial dysmorphism, brain abnormalities including intracerebral calcifications, and neonatal lethal course.
Epidemiology
Ten cases in eight families have been reported, the majority of a Middle East origin. Parental consanguinity was frequently present.
Clinical description
The cranial features are a wide anterior fontanelle, expressed proptosis with everted lower eyelids, severely depressed nasal bridge, small nose, low-set ears, and severe midface hypoplasia leading to choanal atresia. The mouth is usually triangular, gum hypertrophy is expressed, and there may be natal teeth and cleft palate/uvula. The radiological findings include generalized osteosclerosis of all bones and the base of the skull, with cortical hyperostosis and periosteal new bone formation. An obtuse mandibular angle is characteristic, as are irregularly formed ribs. Radiologically, widespread bilateral calcification in the periventricular white matter, basal ganglia, and thalamus is found and in some cases calcifications are also seen in the corpus callosum, falx, tentorium, and meninges. Extra-skeletal features can be hydronephrosis and ureteral stenosis.
Etiology
Mutations in the FAM20C gene have a causative role in lethal osteosclerotic bone dysplasia.
Diagnostic methods
Diagnosis is based on clinical presentation and calcification demonstrable by ultrasound, plain X-rays and computing tomography (CT).
Antenatal diagnosis
Prenatal diagnosis by ultrasound or molecular testing is feasible.
Genetic counseling
The condition is transmitted in an autosomal recessive manner.

                            Last update: 
                            February 2008


                            - Expert reviewer(s): 
                            Pr Raoul HENNEKAM
Otodental syndrome (ORPHA:2791)
Otodental syndrome is a very rare inherited condition characterized by grossly enlarged canine and molar teeth (globodontia) associated with sensorineural hearing loss.
Epidemiology
Prevalence of this disorder is not known. It has been described in about 10 families of European, Chinese and Brazilian descent.
Clinical description
Patients have striking pathognomonic dental features characterized by globodontia of the primary and secondary dentition, sparing the incisors. Missing teeth, especially premolars, are also reported. Due to abnormal crown morphology, there is a great propensity to formation of caries. There is a high rate of endodontic-periodontic lesions due to the aberrant coronal and pulpal morphology. The dental conditions are associated with bilateral sensorineural high-frequency hearing deficit with an age of onset that varies from early childhood to middle age. Variable facial dysmorphism has also been reported. One family was found to have an associated bilateral iris and retinal ocular coloboma.
Etiology
Haploinsufficiency in the fibroblast growth factor 3 (FGF3) gene (11q13) has been reported in patients with otodental syndrome and is thought to cause the phenotype. In the family with the associated ocular coloboma, a microdeletion in the Fas-associated death domain (FADD) gene (11q13.3) was found to be responsible for ocular features.
Diagnostic methods
The dental findings are diagnostic. Molecular genetic testing confirms the diagnosis.
Differential diagnosis
Although the association of sensorineural hearing loss and dental anomalies can be found in other syndromes, none display the striking dental manifestations of otodental syndrome.
Genetic counseling
The condition appears to be inherited in an autosomal dominant manner with complete to variable penetrance and variable expressivity. Genetic counseling should be offered to affected families.
Management and treatment
Dental management is complex, interdisciplinary and requires regular follow up, scheduled tooth extraction and eventually orthodontic treatment. Monitoring of hearing and, if necessary, hearing aids are mandatory. A preventive program is mandatory in order to maintain proper oral hygiene and health. Endodontic therapy can be difficult due to duplicated pulp canals in the affected posterior teeth. Multiple extractions may be needed and fixed or removable prostheses should be constructed. Implants are also a potential consideration.
Prognosis
The functional prognosis is mostly good with appropriate dental treatment and hearing aids. Quality of life may be affected by psychological and functional aspects.

                            Last update: 
                            November 2012


                            - Expert reviewer(s): 
                            Pr Agnès BLOCH-ZUPAN
Otofaciocervical syndrome (ORPHA:2792)
Otofaciocervical syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by distinct facial features (long triangular face, broad forehead, narrow nose and mandible, high arched palate), prominent, dysmorphic ears (low-set and cup-shaped with large conchae and hypoplastic tragus, antitragus and lobe), long neck, preauricular and/or branchial fistulas and/or cysts, hypoplastic cervical muscles with sloping shoulders and clavicles, winged, low, and laterally-set scapulae, hearing impairment and mild intellectual deficit. Vertebral defects and short stature may also be associated.
Otoonychoperoneal syndrome (ORPHA:2793)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by the association of dysplastic external ears, nail hypoplasia, and variable skeletal malformations, such as hypoplastic or absent fibulae, abnormalities of the scapula, clavicle, and acromioclavicular joint, and talipes equinovarus, among others. Joint contractures and mild facial dysmorphism have also been reported.
Otopalatodigital syndrome spectrum disorder (ORPHA:364541)
Otopalatodigital syndrome spectrum disorder is a primary bone dysplasia and encompasses a group of congenital anomalies that are characterized by skeletal dysplasia of varying clinical severity and an X linked dominant pattern of inheritance. This group includes otopalatodigital syndrome type 1 and 2 (OPD1, OPD2) which are characterized in affected males by cleft palate, conductive hearing loss, craniofacial abnormalities and skeletal dysplasia; Melnick-Needles syndrome (MNS) which displays skeletal deformities in females and embryonic or perinatal lethality in most males; frontometaphyseal dysplasia (FMD); and terminal osseous dysplasia - pigmentary defects.