Congenital cataracts facial dysmorphism neuropathy syndrome, a novel complex genetic disease in Balkan gypsies: Clinical and electrophysiological observations

During a study of hereditary motor and sensory neuropathy-Lom in Bulgaria, a previously unrecognized neurological disorder was encountered, mainly in Wallachian Gypsies, who represent a relatively recent genetic isolate. The disorder has been termed the congenital cataracts facial dysmorphism neurop athy (CCFDN) syndrome to emphasize its salient features. Fifty individuals from 19 extended pedigrees were identified and examined clinically and elec trophysiologically. At least 1 patient from each family was admitted to the hospital in Sofia for full investigation. Pedigree analysis indicates auto somal recessive inheritance. The disorder is recognized in infancy by the p resence of congenital cataracts and microcorneas. A predominantly motor neu ropathy beginning in the lower limbs and later affecting the upper limbs de velops during childhood and leads to severe disability by the third decade. Associated neurological features are a moderate nonprogressive cognitive d eficit in most affected individuals together with pyramidal signs and mild chorea in some. Accompanying nonneurological features include short stature , characteristic facial dysmorphism, and hypogonadotrophic hypogonadism. Ne rve conduction studies suggest a hypomyelinating/demyelinating neuropathy, confirmed by nerve biopsy. The CCFDN syndrome is thus a pleomorphic autosom al recessive disorder displaying a combination of neurological and nonneuro logical features.