Syndactyly, tremor, and hypomyelination associated with oculodentodigital dysplasia

Oculodentodigital dysplasia (ODDD, OMIM #164200) is a rare syndrome of autosomal dominant inheritance typically presenting with ophthamologic abnormalities, teeth anomalies, syndactyly and malformations of the 4th and 5th digit. Various neurologic symptoms can be associated. We report on a 4 9/12 years old boy referred to us because of shaking of his hands during activity for 6 months. The symptoms were worse in the morning. He avoided activities requiring fine motor skills. Medical history revealed that he was born with bilateral syndactyly of the 4th and 5th finger requiring surgical separation. Physical examination showed bilateral action and intention tremor without resting or postural tremor, dysmetria, or gait disturbance. Except for mild hyperopia and astigmatism, ophthalmologic examination was normal. He had a dry, scaling skin in the periorbital region and epicanthic folds. Cranial MRI showed mild hypomyelination with better myelination of the subcortical fibres and also T2 hyperintense signal abnormalities in the pons and the middle cerebellar peduncles. On examination at 43 years of age, his father showed yellowish teeth requiring constant care for caries, status after surgery for partial IV/V syndactyly of the left hand, hyperkeratotic skin lesions in different regions of his body and mildly hypoplastic nasal alae. Uni- or bilateral IV/V syndactyly was also present in the patient's sister who also had yellowish teeth and severe caries, a paternal uncle and the grandmother. Suspecting ODDD because of mild hypomyelination, teeth anomalies and syndactyly, analysis of the connexion 43 (GJA1) gene was performed showing a novel heterozygous sequence change, c.17C>G, p.A6G, which has not yet been causally associated with ODDD. Segregation studies in the family are pending. This case report underlines the importance of associated abnormalities in the differenzial diagnosis of hypomyelination. It also confirms that ODDD shows variable intrafamilial expressivity and that (mild) neurological symptoms are probably quite frequent in patients with ODDD.