Phenotype of Charcot-Marie-Tooth disease Type 2.
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.
Bienfait
H M E
HM
Department of Neurology, Academic Medical Centre, University of Amsterdam, The Netherlands.
Baas
F
F
Koelman
J H T M
JH
de Haan
R J
RJ
van Engelen
B G M
BG
Gabreëls-Festen
A A W M
AA
Ongerboer de Visser
B W
BW
Meggouh
F
F
Weterman
M A J
MA
De Jonghe
P
P
Timmerman
V
V
de Visser
M
M
D000200:Action Potentials; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001369:Axons / Q000502:physiology; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003711:Demyelinating Diseases; D004576:Electromyography; D005260:Female; D020558:GTP Phosphohydrolases; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics* / Q000502:physiology; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D006987:Hypesthesia / Q000209:etiology; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000502:physiology; D018908:Muscle Weakness / Q000209:etiology; D009133:Muscular Atrophy / Q000209:etiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009426:Netherlands / Q000453:epidemiology; D009431:Neural Conduction; D009460:Neurologic Examination; D010525:Peripheral Nerves / Q000503:physiopathology; D010641:Phenotype; D012021:Reflex, Abnormal; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016138:Walking; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D000090802:rab7 GTP-Binding Proteins
C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; D020691:rab GTP-Binding Proteins