Alternative titles; symbols
SNOMEDCT: 45853006; ICD10CM: G60.0; ORPHA: 3115;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q23.3 | Roussy-Levy syndrome | 180800 | Autosomal dominant | 3 | MPZ | 159440 |
| 17p12 | Roussy-Levy syndrome | 180800 | Autosomal dominant | 3 | PMP22 | 601097 |
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).
Roussy-Levy syndrome is an autosomal dominant disorder characterized by early onset of prominent ataxia followed by late onset of mild motor involvement. Symptoms progress very slowly, and affected individuals may remain ambulatory throughout life (Auer-Grumbach et al., 1998; Plante-Bordeneuve et al., 1999).
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).
The transmission pattern of Roussy-Levy syndrome in the families studied by Auer-Grumbach et al. (1998) and Plante-Bordeneuve et al. (1999) was consistent with autosomal dominant inheritance.
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.
Auer-Grumbach, M., Strasser-Fuchs, S., Wagner, K., Korner, E., Fazekas, F. Roussy-Levy syndrome is a phenotypic variant of Charcot-Marie-Tooth syndrome IA associated with a duplication on chromosome 17p11.2. J. Neurol. Sci. 154: 72-75, 1998. [PubMed: 9543325] [Full Text: https://doi.org/10.1016/s0022-510x(97)00218-9]
Lapresle, J. Contribution a l'etude de la dystasie areflexique hereditaire. Etat actuel de quatre des sept cas princeps de Roussy et Mlle. Levy, trente ans apres la premiere publication de ces auteurs. Sem. Hop. Paris 32: 2473-2482, 1956. [PubMed: 13360305]
Plante-Bordeneuve, V., Guiochon-Mantel, A., Lacroix, C., Lapresle, J., Said, G. The Roussy-Levy family: from the original description to the gene. Ann. Neurol. 46: 770-773, 1999. [PubMed: 10553995] [Full Text: https://doi.org/10.1002/1531-8249(199911)46:5<770::aid-ana13>3.0.co;2-u]
Rombold, C. R., Riley, H. A. The abortive type of Friedreich's disease. Arch. Neurol. Psychiat. 16: 301-312, 1926.
Roussy, G., Levy, G. Sept cas d'une maladie familiale particulaiere. Rev. Neurol. 45: 427-450, 1926.
Roussy, G., Levy, G. A propos de la dystasie areflexique hereditaire. Rev. Neurol. 62: 763-773, 1934.
Rozanski, J. Hereditary areflexic dystasia: report on a family with Roussy-Levy disease in Israel. Monatsschr. Psychiatr. Neurol. 122: 141-156, 1951. [PubMed: 14863318]
Symonds, C. P., Shaw, M. E. Familial claw-foot with absent tendon jerks. Brain 49: 387-403, 1926.
Thomas, P. K., Calne, D. B., Stewart, G. Hereditary motor and sensory polyneuropathy (peroneal muscular atrophy). Ann. Hum. Genet. 38: 111, 1974. [PubMed: 4467779] [Full Text: https://doi.org/10.1111/j.1469-1809.1974.tb01945.x]
Yudell, A., Dyck, P. J., Lambert, E. H. A kinship with the Roussy-Levy syndrome. Arch. Neurol. 13: 432-440, 1965. [PubMed: 5834704] [Full Text: https://doi.org/10.1001/archneur.1965.00470040098016]