HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) All Versions of this Article: jnnp.2006.093443v1 77/10/1169    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berciano, J Articles by Combarros, O Search for Related Content PubMed PubMed Citation Articles by Berciano, J Articles by Combarros, O

Charcot–Marie–Tooth disease type 1A duplication with severe paresis of the proximal lower limb muscles: a long-term follow-up study

¹ Service of Neurology, University Hospital Marqués de Valdecilla-IFIMAV, University of Cantabria, Santander, Spain
² Service of Radiology, University Hospital Marqués de Valdecilla-IFIMAV
³ Service of Clinical Neurophysiology, University Hospital Marqués de Valdecilla-IFIMAV

Correspondence to:
Correspondence to:
J Berciano
Service of Neurology, University Hospital Marqués de Valdecilla-IFIMAV, University of Cantabria, 39008 Santander, Spain; jaberciano{at}humv.es

Objective: To describe a large pedigree with Charcot–Marie–Tooth disease type 1A (CMT1A) duplication in which severe pelvic and thigh musculature weakness occurred in two patients, detected by analysing the leg muscle atrophy pattern on magnetic resonance imaging (MRI).

Methods: The pedigree comprised 18 patients, aged between 15 and 85 (median 46) years, who were serially evaluated for up to three decades. All 18 patients and 13 non-affected at-risk people underwent electrophysiological examination. An MRI study of lower limb musculature was carried out in four patients. Three patients underwent sural-nerve biopsy. Genetic testing was carried out in 17 patients and in all 13 at-risk normal people.

Results: Fourteen patients were asymptomatic or slightly disabled. The two oldest patients, aged 84 and 80, showed a moderate phenotype. Two other patients, aged 70 and 53, showed late-onset and gradually progressive peroneal paresis extending up to the thigh and pelvic musculature, resulting in waddling gait. MRI scans of all three patients with a mild phenotype showed subtle and subclinical fatty infiltration of calf anterolateral muscle compartments, with thigh muscle involvement in one patient, and extensive atrophy of intrinsic foot muscles. In the youngest patient with proximal leg weakness, the MRI scan showed massive fatty atrophy of all the calf muscles, posteromedial thigh muscle compartments, and internal and external hip rotator muscles. Sural-nerve biopsy specimens showed hypertrophic neuropathy with no superimposed inflammation. Good correlation was seen between electrophysiological and genetic testing.

Conclusions: Late in the clinical course, a small proportion of patients with CMT1A develop severe proximal leg weakness, and long-term follow-up is essential for its detection. MRI scans may show subclinical involvement of the thigh musculature.

Abbreviations: CIDP, chronic inflammatory demyelinating polyneuropathy; CMAP, compound muscle action potential; CMT1A, Charcot–Marie–Tooth disease type 1A; CMTNS, CMT Neuropathy Score; DML, distal motor latency; EMG, electromyogram; FDS, Functional Disability Scale; MCV, motor conduction velocity; MRC, Medical Research Council; MRI, magnetic resonance imaging; MUP, motor unit potential; SCV, sensory conduction velocity; SNAP, sensory nerve action potential; TLI, terminal latency index; TR/TE, repetition time/echo time

This article has been cited by other articles:

				J Berciano, E Gallardo, R Dominguez-Perles, E Gallardo, A Garcia, R Garcia-Barredo, O Combarros, J Infante, and I Illa Autosomal-dominant distal myopathy with a myotilin S55F mutation: sorting out the phenotype J. Neurol. Neurosurg. Psychiatry, February 1, 2008; 79(2): 205 - 208. [Abstract] [Full Text] [PDF]