Neurological presentations of oculodentodigital dysplasia

Abstract

Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant disorder caused by mutations in connexin 43 gene GJA1. Typical features are syndactyly of IV-V or III-V fingers with/without feet syndactyly, anomalies of eyes, teeth, hair and nose. In about 30% of patients neurological disorders appear later in life: progressive spastic paraparesis, neurogenic bladder/bowel, ataxia, white matter lesions on MRI. First Russian DNA-confirmed ODDD cases are presented: 4 unrelated families with 5 affected women age 10-59 yrs. In addition to typical congenital anomalies all patients had neurological symptoms (mainly spastic paraparesis) with different age of onset. In three cases, preliminary diagnoses were hereditary neurodegenerations, only in one patient ODDD was recognized earlier. In GJA1 gene three novel mutations were detected: c.400_402delAAG (in two families), с.461C>T (p.Thr154Ile) and с.94T>G (p.Phe32Val). De novo origin of mutations in three sporadic cases was proved by parent DNA testing; in the familial case, the mutation in elder patient also obviously occurred de novo.