HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Williams, D. R. Articles by Byrne, E. Search for Related Content PubMed PubMed Citation Articles by Williams, D. R. Articles by Byrne, E. Related Collections Muscle disease

A new dominant distal myopathy affecting posterior leg and anterior upper limb muscles

From St. Vincent’s Hospital (Drs. Williams, Reardon, Roberts, and Byrne), Melbourne; State Neuropathology Service (Drs. Reardon and Dennet) and Department of Medicine (Dr. Byrne), University of Melbourne, Victoria; and Centre for Neuromuscular and Neurological Disorders (Drs. Duff and Laing) and Centre for Medical Research (Dr. Laing), University of Western Australia, Nedlands, Australia. Dr. Williams is currently affiliated with Queen Square Brain Bank for Neurological Diseases, London, England. Prof. Ed Byrne is currently affiliated with the Faculty of Medicine, Nursing & Health Sciences, Monash University, Australia.

Address correspondence and reprint requests to Dr. David Williams, Queen Square Brain Bank for Neurological Diseases, 1 Wakefield St., London WC1N 1PJ, UK; e-mail: drdavew{at}bigpond.com

Objective: To report a dominant, slowly progressive early onset distal myopathy with sparing of the tibialis anterior.

Methods: Twelve affected and two possibly affected members from an Australian kindred were examined and investigated by EMG, imaging studies, histopathology, and genetic analysis.

Results: Affected patients had a slowly progressive condition with symmetric, distal weakness and wasting of the anterior upper and posterior lower limbs, with sparing of tibialis anterior, even in advanced disease. All patients remained ambulant and there was no evidence of cardiac or respiratory muscle involvement. Serum creatine kinase levels were either normal or mildly elevated. Imaging studies showed widespread involvement of the posterior and lateral leg compartments. Proximal muscles were radiologically abnormal only in advanced disease. Muscles that were mildly affected clinically appeared normal on imaging. EMG in nine patients showed widespread myopathic changes. Muscle histopathology in four patients showed either end stage muscle or nonspecific myopathic findings without inflammation or vacuoles. Microsatellite markers for distal myopathy loci were analyzed and all known distal myopathy phenotype genes and linkage regions were formally excluded by multipoint analysis.

Conclusions: The affected patients in this kindred display a clinically distinct myopathy, with selective involvement of posterior lower and anterior upper limb muscles. The genetic analysis suggests the existence of one more distal myopathy locus.

The genetics component of this work was supported by the Australian National Health and Medical Research Council Fellowship grant 139170 and Project Grant 254544 and by the US Muscular Dystrophy Association.

Received March 11, 2004. Accepted in final form December 3, 2004.