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From the Department of Neurology (H.M.E.B. M.d.V.), Unit of Clinical Neurophysiology (J.H.T.M.K., B.W.O.d.V.), Neurogenetics Laboratory (F.B., F.M., M.A.J.W.), and Department of Clinical Epidemiology and Biostatistics (R.J.d.H.), Academic Medical Center, University of Amsterdam, The Netherlands; Institute of Neurology, University Medical Center St. Radboud, Nijmegen, The Netherlands (A.A.W.M.G.-F., B.G.M.v.E.); and Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium (P.D.J., V.T.).
Address correspondence and reprint requests to Dr. M. de Visser, Department of Neurology, Academic Medical Centre, PO Box 22660, 1100 DD Amsterdam, The Netherlands M.deVisser{at}amc.uva.nl.
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.
Editorial, see page 1649.
Supported by the Prinses Beatrix Fonds The Hague, The Netherlands.
Disclosure: The authors report no conflicts of interest.
Received November 29, 2006. Accepted in final form March 6, 2007.
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