Abstract

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.