Roussy-Levy Hereditary Areflexic Dystasia

A number sign (#) is used with this entry because Roussy-Levy syndrome can be caused by heterozygous mutation in the peripheral myelin protein-22 gene (PMP22; 601097) or the myelin protein zero gene (MPZ; 159440).

Clinical Features

The condition was described independently by Roussy and Levy (1926), by Symonds and Shaw (1926), who called it 'familial claw-foot with absent tendon jerks', and by Rombold and Riley (1926), who called it an 'abortive type of Friedreich disease' (229300). This disorder usually begins in infancy or childhood and manifests as a delay in starting to walk with clumsiness and frequent falls. This condition resembles Charcot-Marie-Tooth disease type 1 (CMT1A; 118200) in its dominant inheritance, foot deformity, weakness and atrophy of distal limb muscles, especially the peronei, absent tendon reflexes, decreased excitability of muscles to galvanic and faradic stimulation, and some distal sensory loss. The syndrome differs in that it includes static tremor of the upper limbs and gait ataxia. Roussy and Levy (1926, 1934) stressed the absence of cerebellar signs, speech disturbances, Babinski sign, and nystagmus. Low conduction velocity of peripheral nerves was a striking feature of the cases reported by Yudell et al. (1965). Rozanski (1951) described a family with affected members in 4 generations and with several instances of male-to-male transmission. Lapresle (1956) gave follow-up information on the family of Roussy and Levy. Thomas et al. (1974) noted the clinical overlap of Roussy-Levy syndrome with Charcot-Marie-Tooth disease type 1 and Dejerine-Sottas syndrome (145900).

Molecular Genetics

Auer-Grumbach et al. (1998) provided evidence suggesting a close relationship between Roussy-Levy syndrome and CMT1A (118220). They found that 3 members of a 4-generation family with Roussy-Levy syndrome carried the classic CMT1A PMP22 duplication (601097.0001). The etiology of the gait ataxia and essential tremor remained unclear.

In members of the original family studied by Roussy and Levy (1926), Plante-Bordeneuve et al. (1999) identified a heterozygous mutation in the myelin protein zero gene (159440.0021); mutations in this gene are also associated with CMT1B (118200). Nerve biopsy of 3 members showed a chronic demyelinating neuropathy with loss of myelinated fibers and focally hypertrophic myelin sheaths.