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

The Marinesco-Sjögren syndrome (MSS) (MIM 248800) is an autosomal recessive condition characterised by cataracts, ataxia, and growth and mental retardation. Chronic myopathy is a common feature. Peripheral neuropathy and acute rhabdomyolysis have been described occasionally in MSS. To date, no gene for it has been localised. Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN) (MIM 604168) is a recently delineated autosomal recessive condition, so far only described in a specific gypsy group originating from Bulgaria. This disorder was localised by linkage analysis to 18qter, telomeric to the marker D18S1141. CCFDN alleles showed a highly conserved haplotype in the region D18S1141-D18S70-D18S1268 consistent with genetic homogeneity and a single founder mutation. Since then, the disease locus has been reduced to the interval located between markers D18S1095 and D18S1390. 4 MSS and CCFDN share common clinical features and are considered to be differential diagnoses. Recently, Merlini et al proposed that the CCFDN syndrome and one subtype of MSS (Marinesco-Sjögren/myoglobinuria), also only described in gypsy patients, are genetically identical. We report here the clinical and linkage analysis of one gypsy family and one Turkish family in which patients presented with congenital or juvenile cataracts and ataxia. Both families were initially diagnosed as MSS. However, our study shows that they are clinically and genetically distinct. We found that the gypsy family had CCFDN features and was linked to 18qter whereas the Turkish family had typical MSS features and was not linked to 18qter. Here, we confirm the clinical overlap between the CCFDN and MS syndromes and show that they are distinct genetic entities.