Phenotype of Charcot-Marie-Tooth disease Type 2

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Neurology. 2007 May 15;68(20):1658-67.

Phenotype of Charcot-Marie-Tooth disease Type 2.

Bienfait HM, Baas F, Koelman JH, de Haan RJ, van Engelen BG,

Gabreels-Festen AA, Ongerboer de Visser BW, Meggouh F, Weterman MA,

De Jonghe P, Timmerman V, de Visser M.

Department of Neurology, Academic Medical Centre, University of

Amsterdam, The Netherlands.

OBJECTIVE: To investigate the clinical and electrophysiologic

phenotype of Charcot-Marie-Tooth disease (CMT) Type 2 in a large

number of affected families.

METHODS: We excluded CMT Type 1, hereditary neuropathy with

liability to pressure palsies, and CMT due to Cx32 gene mutations by

DNA analysis. We performed genetic analysis of the presently known

CMT Type 2 genes.

RESULTS: Sixty-one persons from 18 families were affected. Ninety

percent of patients were able to walk with or without the help of

aids. Proximal leg muscle weakness was present in 13%. Asymmetrical

features were present in 15%. Normal or brisk knee reflexes were

present in 36%. Extensor plantar responses without associated

spasticity occurred in 10 patients from eight families. Only three

causative mutations were identified in the MFN2, BSCL2, and RAB7

genes. No mutations were found in the NEFL, HSPB1, HSPB8, GARS,

DNM2, and GDAP1 genes.

CONCLUSIONS: At group level, the clinical phenotype of Charcot-Marie-

Tooth disease (CMT) Type 2 is uniform, with symmetric, distal

weakness, atrophy and sensory disturbances, more pronounced in the

legs than in the arms, notwithstanding the genetic heterogeneity.

Brisk reflexes, extensor plantar responses, and asymmetrical muscle

involvement can be considered part of the CMT Type 2 phenotype. The

causative gene mutation was found in only 17% of the families we

studied.