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

Abstract

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 neuropathy (CCFDN) syndrome to emphasize its salient features. Fifty individuals from 19 extended pedigrees were identified and examined clinically and electrophysiologically. At least 1 patient from each family was admitted to the hospital in Sofia for full investigation. Pedigree analysis indicates autosomal recessive inheritance. The disorder is recognized in infancy by the presence of congenital cataracts and microcorneas. A predominantly motor neuropathy beginning in the lower limbs and later affecting the upper limbs develops during childhood and leads to severe disability by the third decade. Associated neurological features are a moderate nonprogressive cognitive deficit 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. Nerve conduction studies suggest a hypomyelinating/demyelinating neuropathy, confirmed by nerve biopsy. The CCFDN syndrome is thus a pleomorphic autosomal recessive disorder displaying a combination of neurological and nonneurological features.

Linkage to 18qter differentiates two clinically overlapping syndromes: congenital cataracts-facial dysmorphism-neuropathy (CCFDN) syndrome and Marinesco-Sjogren syndrome

“…1 Indeed, in family 2, the male patient was the only affected person presenting dysmorphic features.…”

Hereditary motor and sensory neuropathy – Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries

“…A number of reports on hereditary neurological disorders among the Roma have been published over the last few years, e.g. limb-girdle muscular dystrophy LGMD2C [9,10], the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome [11,12] and congenital myasthenia [13,14] and this population is likely to attract interest in the future as well.…”

Genetic studies of the Roma (Gypsies): a review

“…The list includes three novel neurological disorders, namely hereditary motor and sensory neuropathies type Lom (HMSN-L) [[37-39]] and type Russe (HMSN-R) [40], and the congenital cataracts facial dysmorphism neuropathy syndrome (CCFDN) [41,42]. …”