The disease is characterized by wide intra- and interfamilial phenotypic variability. The typical craniofacial anomalies include a thin nose with hypoplastic alae nasi, small anteverted nares and a prominent columella, mandibular overgrowth, cleft palate, and microcephaly. Skeletal manifestations consist of syndactyly (involving the 4th and 5th fingers and/or 2nd to 4th toes), camptodactyly, and clinodactyly due to hypoplasia or aplasia of the middle phalanges. Cranial hyperostosis and broad tubular bones may be present. Ophthalmic anomalies include decreased visual acuity, microphthalmia, microcornea, cataracts, glaucoma, iris abnormalities and optic atrophy. Less frequent ocular findings are nystagmus, palpebral fissure hypoplasia, epicanthal folds and convergent strabismus. The majority of patients with ODDD have abnormal primary and permanent dentition with microdontia, partial anodontia, enamel hypoplasia, multiple caries and early tooth loss. Neurologic symptoms are inconsistent but frequent and include dysarthria, neurogenic bladder disturbances, spastic paraparesis, ataxia, anterior tibial muscle weakness, and seizures. Some patients have dysplastic ears and conductive hearing loss. Mild psychomotor delay has been described. Brain magnetic resonance imaging (MRI) may show white matter abnormalities. Brittle nails and hair abnormalities (hypotrichosis and slow growth) may be present.
ODDD is caused by heterozygous mutations in the GJA1 gene (6q22-q23), which encodes the gap junction protein connexin 43 (Cx43).
