TaoMedAI/RareMedData huggingface dataset:
Dentinogenesis imperfecta type 2 (ORPHA:166260)
Dentinogenesis imperfecta type 2 (DGI-2) is a rare, severe form of dentinogenesis imperfecta (DGI, see this term) and is characterized by weakness and discoloration of all teeth.
Epidemiology
Prevalence of DGI-2 is reported to be 1/6,000 to 1/8,000.
Clinical description
The dental features of DGI-2 are typically bulbous crowns with marked cervical constriction along with amber translucent discoloration and tooth attrition. Roots are generally short and constricted. Both primary and permanent teeth present pulp obliteration. Patients with this form of DGI have no normal teeth. Sensorineural hearing loss has also been found in some patients.
Etiology
DGI-2 is caused by mutations in the DSPP gene (4q21.3) coding for dentin sialophosphoprotein, a precursor for dentin sialoprotein and dentin phosphoprotein which are involved in dentinogenesis.
Diagnostic methods
Diagnosis is based on history, clinical examination and radiographic features. Molecular genetic testing can be used to confirm the diagnosis.
Differential diagnosis
Differential diagnoses include conditions that may have similar clinical or radiographic features to DGI such as osteogenesis imperfecta and dentin dysplasia (see this term). The clinical symptoms may be mistaken for hypocalcified amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann syndrome, cyclic neutropenia, Chediak-Hegashi syndrome, Langerhans cell histiocytosis, Papillon-Lefèvre syndrome), vitamin D-resistant rickets (see these terms), as well as permanent teeth discoloration due to tetracyclines, and vitamin D-dependent rickets. It is important to investigate for a history of bone fractures with minimal trauma, hearing loss and to check for blue sclerae to rule out osteogenesis imperfecta (see this term).
Genetic counseling
DGI-2 follows an autosomal dominant pattern of inheritance. There is therefore a 50% risk that a child born to an affected parent will have the condition.
Management and treatment
Protection of primary and then permanent teeth with preformed pediatric crowns, cast occlusal onlays on first permanent molars and eventually premolars, may help to minimize tooth wear and maintain the occlusal vertical dimension. Obliteration of pulp spaces in teeth that develop abscesses makes endodontic treatment extremely difficult if not impossible. Appropriate care makes it possible to achieve good esthetic appearance and functional performance. The replacement of teeth might be considered with dentures or implants.
Prognosis
Prognosis depends primarily on the age of diagnosis and the quality of management. Early diagnosis and regular dental care cannot always prevent premature tooth loss.

                            Last update: 
                            September 2012


                            - Expert reviewer(s): 
                            Pr Agnès BLOCH-ZUPAN
Dentinogenesis imperfecta type 3 (ORPHA:166265)
Dentinogenesis imperfecta type 3 (DGI-3) is a rare, severe form of dentinogenesis imperfecta (DGI, see this term) characterized by opalescent primary and permanent teeth, marked attrition, large pulp chambers, multiple pulp exposure and shell teeth radiographically (i.e. teeth which appear hollow due to dentin hypotrophy).
Epidemiology
Prevalence of DGI-3 is not known. The disease was identified in the Brandywine isolate in southern Maryland, USA.
Clinical description
In DGI-3, both primary and permanent dentition are affected and teeth are often opalescent. Enamel loss and excessive wear have been reported, as well as marked tooth attrition. DGI-3 is associated with multiple periapical radiolucencies in noncarious teeth.
Etiology
The disorder is caused by mutations in the DSPP gene (4q21.3) coding for dentin sialophosphoprotein, a precursor for dentin sialoprotein and dentin phosphoprotein which are involved in dentinogenesis.
Genetic counseling
Transmission is autosomal dominant.

                            Last update: 
                            September 2012


                            - Expert reviewer(s): 
                            Pr Agnès BLOCH-ZUPAN
Dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome (ORPHA:71267)
A rare malformative syndrome with dentinogenesis imperfecta, characterized by dentin dysplasia with opalescent discoloration and severe attrition of primary and permanent teeth, and delayed eruption, bulbous crowns, long and tapered roots, and progressive root canal obliteration of the permanent dentition, associated with proportionate short stature, sensorineural hearing loss, mild intellectual disability, and dysmorphic facial features. The latter include a prominent nose with high nasal bridge and short philtrum. Osteoporosis, mild platyspondyly, and cone-shaped epiphyses have also been reported.
Dentinogenesis imperfecta (ORPHA:49042)
Dentinogenesis imperfecta (DGI) is a hereditary dentin defect (see this term) characterized by abnormal dentin structure resulting in abnormal tooth development.
Epidemiology
Prevalence of DGI is reported to be 1/6,000 to 1/8,000.
Clinical description
Signs of the condition are variable and there is significant overlap between different types of dentin dysplasia (DD, see this term) and dentinogenesis imperfecta. Three different types of DGI were originally described in the Shield's classification: DGI type 1, type 2 and type 3. The condition formerly known as DGI-1 is now considered to be a syndromic form of DGI associated with osteogenesis imperfecta types 1b,c, 2, 3, 4b, 9, and 10. In dentinogenesis imperfecta type 2 (DGI-2, see this term), osteogenesis imperfecta is not a feature and the condition is usually characterized by abnormal amber or opalescent dentin, worn teeth, bulbous crowns with cervical constriction, short roots, obliterated pulp chambers and root canals (visible on X-rays). Dentinogenesis imperfecta type 3 (DGI-3, see this term) is characterized by opalescent primary and permanent teeth, marked attrition, and large pulp chambers.
Etiology
DGI is a hereditary condition caused by missense and nonsense mutations in the DSPP gene (4q21.3) encoding the major proteins involved in dentin formation.
Genetic counseling
DGI follows an autosomal dominant pattern of inheritance.

                            Last update: 
                            September 2012


                            - Expert reviewer(s): 
                            Pr Agnès BLOCH-ZUPAN
Dermatitis herpetiformis (ORPHA:1656)
A chronic autoimmune subepidermal bullous disease characterized by grouped pruritic lesions such as papules, urticarial plaques, erythema, and herpetiform vesiculae, with a predominantly symmetrical distribution on extensor surfaces of the elbows (90%), knees (30%), shoulders, buttocks, sacral region, and face of children and adults. Erosions, excoriations and hyperpigmentation usually follow. It may also appear as a consequence of gluten intolerance.
Dermatoleukodystrophy (ORPHA:1659)
A rare leukodystrophy characterized by congenital thickened, wrinkled skin showing loss of elasticity, in combination with childhood onset of rapidly progressive generalized cognitive and motor impairment quickly resulting in a vegetative state and early death. Neuropathologic examination reveals neuroaxonal leukodystrophy with numerous neuroaxonal spheroids and diffuse loss of axons and myelin sheaths.
Dermatoosteolysis, Kirghizian type (ORPHA:1657)
A rare genetic disease characterized by infantile onset of recurrent skin ulcerations, arthralgias, fever, peri-articular fistulous osteolysis, oligodontia, nail dystrophy, and keratitis. The disease takes a self-limiting course in childhood but results in severe cicatrization, chronic arthroses, pseudoacromegalic appearance of hands and feet, secondary scoliosis, and visual impairment. There have been no further descriptions in the literature since 1983.
Dermatopathia pigmentosa reticularis (ORPHA:86920)
A rare, genetic, ectodermal dysplasia characterized by a widespread, early-onset, reticulate hyperpigmentation that persists throughout life, mild, diffuse non-cicatricial alopecia, and onychodystrophy. There are no dental anomalies. Patients may also present with adermatoglyphia, palmoplantar hyperkeratosis, acral dorsal blistering, and hypohidrosis or hyperhidrosis.
Dermatosparaxis Ehlers-Danlos syndrome (ORPHA:1901)
A form of Ehlers-Danlos syndrome (EDS) characterized by extreme skin fragility and laxity, a prominent facial gestalt, excessive bruising and, sometimes, major complications due to visceral and vascular fragility.
Dermochondrocorneal dystrophy (ORPHA:79149)
Dermochondrocorneal dystrophy is characterised by osteochondrodystrophy of the hands and feet, corneal dystrophy and the presence of skin nodules clustered around the metacarpophalangeal and interphalangeal joints, around the nose and ears and on the posterior surface of the elbow. Gingival lesions may also be present. It has been described in less than 20 patients. Transmission is autosomal recessive.
Dermoid or epidermoid cyst of the central nervous system (ORPHA:530033)
A rare congenital tumor characterized by a benign cyst with epithelial and epidermoid components, originating from embryologic displacement and ectopic growth of ectodermal tissue in the central nervous system. In contrast to epidermoid cysts, dermoid cysts also contain dermis and skin appendages. Most common location is the lumbosacral region, as well as the cerebellopontine angle and parasellar area for intracranial lesions. Clinical presentation depends on the location and size of the tumor and includes pain, muscle weakness, motor and sensory disturbances, and incontinence for intraspinal lesions, and intracranial hypertension, gait disturbances, cranial nerve dysfunction, and visual deficits for intracranial tumors. The cysts may rupture and cause chemical meningitis.
Dermoodontodysplasia (ORPHA:1660)
A rare ectodermal dysplasia syndrome characterized by a variably severe clinical picture comprising dry, thin skin, onychodysplasia, trichodysplasia, and dental abnormalities (such as hypodontia, microdontia, and persistence of deciduous teeth). There have been no further descriptions in the literature since 1990.
Dermotrichic syndrome (ORPHA:99688)
A rare, genetic, ectodermal dysplasia syndrome characterized by skin, hair and nail anomalies (i.e. generalized ichthyosis, congenital alopecia universalis, dystrophic, convex nails), associated with hypohidrosis without hyperthermia, intellectual disability, seizures, and skeletal (e.g. proportionate short stature, platyspondyly) and intestinal (e.g. congenital aganglionic megacolon) anomalies. Facial dysmorphism includes frontal bossing, blepharophimosis, large ears, low nasal bridge and small nose. There have been no further descriptions in the literature since 1992.
Desmin-related myopathy with Mallory body-like inclusions (ORPHA:84132)
A rare inclusion myopathy characterized by hypotonia and axial muscle weakness leading to spinal rigidity and development of scoliosis and other deformities which can result in respiratory failure. The symptoms are apparent from birth or early childhood. The muscle weakness is not progressive, and most patients remain ambulatory. Muscle biopsies show variable myopathic changes.
Desminopathy (ORPHA:98909)
A rare genetic skeletal muscle disease characterized by abnormal chimeric aggregates of desmin and other cytoskeletal proteins and granulofilamentous material at the ultrastructural level in muscle biopsies and variable clinical myopathological features, age of disease onset and rate of disease progression. Patients present with bilateral skeletal muscle weakness that starts in distal leg muscles and spreads proximally, sometimes involving trunk, neck flexors and facial muscles and often cardiomyopathy manifested by conduction blocks, arrhythmias, chronic heart failure, and sometimes tachyarrhythmia. Weakness eventually leads to wheelchair dependence. Respiratory insufficiency can be a major cause of disability and death, beginning with nocturnal hypoventilation with oxygen desaturation and progressing to daytime respiratory failure.
Desmoplastic infantile astrocytoma/ganglioglioma (ORPHA:251940)
Desmoplastic infantile astrocytoma/ganglioglioma are mixed neuronal-glial tumors representing a histological spectrum of the same tumor. They are usually supratentorially located, large, cystic masses with a peripheral solid component, characterized by prominent desmoplastic stroma and pleomorphic populations of neoplastic cells with either astrocytic or ganglionic differentiation and poorly differentiated cells in variable proportions. They usually present in the first 18 months of age with rapid head growth, bulging anterior fontanel and bone structures over the tumor, signs of raised intracranial pressure (headache, vomiting, papilledema), focal neurological signs and sometimes seizures.
Desmoplastic/nodular medulloblastoma (ORPHA:251863)
Desmoplastic/nodular medulloblastoma is a histological variant of medulloblastoma (see this term), an embryonic malignancy, often located in one of the cerebellar hemispheres, occurring most frequently in adults and manifesting with symptoms such as vomiting and headache.
Desmosterolosis (ORPHA:35107)
Desmosterolosis is a very rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, and intellectual disability, with elevated levels of desmosterol.
Epidemiology
Only 9 cases have been reported in the literature to date.
Clinical description
Desmosterolosis presents at birth with growth restriction, spasticity with variable degrees of hand contractures, either microcephaly or relative macrocephaly, and microretrognathia. Transient neonatal seizures, nystagmus, strabismus and failure to thrive are also seen in most cases. Intellectual disability occurs in all patients and is first noted by delayed milestones for speech and adaptive, fine and gross motor development. Less common manifestations reported include hirsutism, facial dysmorphism (downslanting palpebral fissures, bilateral epicanthal folds, submucous cleft palate, and thick alveolar ridges), sensorineural hearing loss, patent arterial duct, ambiguous genitalia, bilateral clubfeet, muscle wasting, and cutis aplasia. Optic atrophy, corpus callosum agenesis and loss of white matter are also noted.
Etiology
Desmosterolosis is due to mutations in the DHCR24 gene (1p32.3) encoding 3-beta-hydroxysterol delta-24-reductase. This enzyme catalyzes the conversion of desmosterol (the cholesterol precursor) to cholesterol, which is highly involved in embryonic development and morphogenesis. Reduced enzyme activity leads to the accumulation of desmosterol and a lack of cholesterol, disrupting antenatal and postnatal development.
Genetic counseling
Desmosterolosis is inherited in an autosomal recessive manner and genetic counseling is possible.

                            Last update: 
                            December 2014


                            - Expert reviewer(s): 
                            Dr Nicola BRUNETTI PIERRI  - Pr Giancarlo PARENTI
Desquamative interstitial pneumonia (ORPHA:98852)
A rare idiopathic interstitial pneumonia characterized by extensive, diffuse intra-alveolar accumulation of pigment-laden macrophages, most commonly associated with long-term exposure to tobacco smoke. Patients present with slowly progressive shortness of breath on exertion and chronic cough with bilateral crackles. Digital clubbing is also frequently observed. Pulmonary function test reveals a restrictive pattern. Computed tomography typically shows diffuse ground-glass opacities with subpleural and lower zone predominance.
Developmental and speech delay due to SOX5 deficiency (ORPHA:313892)
Developmental and speech delay due to SOX5 deficiency is a rare genetic syndromic intellectual disability characterized by mild to severe global developmental delay, intellectual disability and behavioral abnormalities, hypotonia, strabismus, optic nerve hypoplasia and mild facial dysmorphic features (down slanting palpebral fissures, frontal bossing, crowded teeth, auricular abnormalities and prominent philtral ridges). Other associated clinical features may include seizures and skeletal anomalies (kyphosis/scoliosis, pectus deformities).
Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency (ORPHA:289307)
A rare, genetic, inborn error of branched-chain amino acid metabolism disorder, with a highly variable clinical and biochemical phenotype, typically characterized by mild to severe global developmental delay, elevated methylmalonic acid and, occasionally, lactic acid plasma levels, and chronic methylmalonic aciduria, which may be accompanied by elevation of additional organic or amino acids in urine (e.g. beta-alanine, methionine, 3-hydroxypropionic, 3-aminoisobutyric and/or 3-hydroxyisobutyric acid). Microcephaly, mild craniofacial dysmorphism, axial hypotonia, liver failure, and central nervous system abnormalities on MRI have also been reported.
Developmental delay with autism spectrum disorder and gait instability (ORPHA:329195)
Developmental delay with autism spectrum disorder and gait instability is a rare, genetic, neurological disorder characterized by infant hypotonia and feeding difficulties, global development delay, mild to moderated intellectual disability, delayed independent ambulation, broad-based gait with arms upheld and flexed at the elbow with brisk walking or running, and limited language skills. Behavior patterns are highly variable and range from sociable and affectionate to autistic behavior.
Developmental delay-facial dysmorphism syndrome due to MED13L deficiency (ORPHA:369891)
A rare, genetic syndromic intellectual disability characterized by developmental delay, mild to severe intellectual disability, facial features (bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance) and a wide spectrum of other nonspecific variable clinical features.
Epidemiology
To date, more than 70 cases have been reported.
Clinical description
Patients have a variable degree of intellectual disability, global developmental delay (notably with severe speech and language impairment), muscular hypotonia, and facial features (including broad forehead, bitemporal narrowing, upslanting palpebral fissures, low-set ears, flat nasal bridge, bulbous nose, thin vermillion border and open mouth with tongue protrusion). Highly variable additional features include cardiac defects (persistent foramen ovale, ventricular septal defects or tetralogy of Fallot), cerebellar ataxia, seizures, growth difficulties, microcephaly, ventriculomegaly or myelination defects.
Etiology
The disorder is sporadic caused by either a sequence variation in the mediator complex subunit 13-like gene (MED13L), an intragenic microdeletion within the gene, or by a larger microdeletion encompassing the entire gene. Rare intragenic microduplications within MED13L are also reported.
Diagnostic methods
The syndrome could be suspected on the association of developmental delay, speech impairment, motor delay, and facial features (notably, an open mouth with a protruding tongue, a thin vermillion border, upslanting palpebral fissures and a bulbous nasal tip). Molecular genetic testing approaches include array-comparative genomic hybridization for microdeletion identification, and sequencing of the entire MED13L coding region for sequence variants (gene panel, exome sequencing).
Differential diagnosis
Some patients share some clinical features observed in Kleefstra syndome, Mowat-Wilson syndrome, Kabuki syndrome and 1p36 microdeletion.
Antenatal diagnosis
Pathogenic variations are de novo. However, very rare cases of parental mosaicism are described and prenatal genetic testing may be possible in such families with a proband. No specific prenatal signs are reported.
Genetic counseling
Most cases arise de novo and thus the sibling recurrence risk is low. The disorder is autosomal dominant with 50% risk of transmission from affect individuals to their offspring; however, transmission of the condition has never been reported.
Management and treatment
Management is mainly supportive and symptomatic. Affected patients should benefit from speech therapy. Development, walking evolution, hearing and vision should be monitored closely.
Prognosis
The prognosis and function consequences are variable and dependent on the associated anomalies and intellectual disability.

                            Last update: 
                            November 2020


                            - Expert reviewer(s): 
                            Dr Jamal GHOUMID | ITHACA* - Dr Thomas SMOL | ITHACA*


                                * European Reference Network
Developmental delay-language impairment-dopa responsive dystonia-parkinsonism syndrome due to 2q24 microdeletion (ORPHA:1617)
2q24 microdeletion syndrome is a chromosomal anomaly consisting of a partial long arm deletion of chromosome 2 and characterized clinically by a wide range of manifestations (depending on the specific region deleted) which can include seizures, microcephaly, dysmorphic features, cleft palate, eye abnormalities (coloboma, cataract and microphthalmia), growth retardation, failure to thrive, heart defects, limb anomalies, developmental delay and autism.
Developmental malformations-deafness-dystonia syndrome (ORPHA:79107)
Developmental malformations-deafness-dystonia syndrome is characterised by the association of midline malformations, sensory hearing loss, and a delayed-onset generalised dystonia syndrome.
Epidemiology
It has been described in two monozygotic twins.
Etiology
The syndrome is caused by a missense point mutation in the gene coding for beta-actin, a nonmuscle actin isoform. Mutations in nonmuscle actin isoforms may be associated with developmental anomalies and neurological disorders such as dystonia.

                            Last update: 
                            June 2006
Dextrocardia (ORPHA:1666)
A rare, congenital, non-syndromic, developmental defect during embryogenesis characterized by positioning of the heart in the right hemithorax, with the base and apex of the heart pointing caudally and to the right, due to abnormalities of embryologic origin that are intrinsic to the heart itself. Situs inversus or situs solitus may be associated, with extracardiac visceral transposition anomalies usually present in the former case and additional cardiac defects (e.g. septal defects, transposition of the great arteries, double-outlet right ventricle, anomalous pulmonary venous return, tetralogy of Fallot) frequently observed in both cases.