The Roussy-Levy family: From the original description to the gene

In 1926, Roussy and Levy described a large family whose members manifested an early onset dominantly inherited gait ataxia, pes cavus, and areflexia, which was eventually associated with distal muscle atrophy postural tremor, and minor sensory lass. Slow nerve conduction and demyelination of nerve f ibers with onion bulb formations in nerve biopsy specimens led to the Rouss y-Levy syndrome (RLS) being considered a variant of demyelinating Charcot-M arie-Tooth disease (CMT-1). In the present article, we report on the long-t erm follow-up, on nerve biopsy findings, and on the underlying molecular ge netic defect in members of the original family studied by Roussy and Levy. All patients mere able to walk during their seventh decade of life. Morphol ogically, a chronic demyelinating neuropathy with the remarkable aspects of a focally hypertrophic myelin sheath and major loss of myelinated fibers w as observed in nerve biopsy specimens of 3 members of this family. Molecula r genetic testing identified a previously unknown heterozygous missense poi nt mutation which yielded an Asn131Lys substitution in the extracellular do main of the myelin protein zero (P-0) These findings show that the Roussy-L evy family belongs to the CMT-1B subtype and has original morphological and genetic features.