OBJECTIVE AND BACKGROUND: To describe three Gypsy families with 
Marinesco-Sjögren syndrome (MSS), demyelinating neuropathy, and recurrent 
episodes of myoglobinuria in five of the six affected subjects. Because these 
families originated from the same genetically isolated founder population as did 
patients with congenital cataracts facial dysmorphism neuropathy (CCFDN) 
syndrome, and because the two syndromes have clinical manifestations in common, 
we hypothesized that the two related, albeit distinct, syndromes may represent 
clinical variants of a single genetic disorder.
METHODS: Clinical studies were conducted and linkage and haplotype analyses were 
performed for the three families. A total of 16 individuals, including the 6 
with MSS and 10 unaffected relatives, were genotyped for six polymorphic 
microsatellite markers from the CCFDN region on 18qter.
RESULTS: Linkage analysis of markers in the 18qter region, where we previously 
had located the CCFDN gene, produced a lod score of 3.55, demonstrating 
colocalization of the gene responsible for MSS with demyelinating neuropathy and 
myoglobinuria with the CCFDN gene. Moreover, the patients with MSS shared the 
conserved marker haplotype found in CCFDN chromosomes.
CONCLUSIONS: These data suggest that Marinesco-Sjögren syndrome with peripheral 
neuropathy and myoglobinuria, and congenital cataracts facial dysmorphism 
neuropathy syndrome are genetically identical and are caused by a single founder 
mutation.