Distal myopathies.
OBJECTIVE
The distal myopathies are a heterogeneous group of disorders that pose a challenge to both the clinician and geneticist. This article summarizes the findings of recent clinical, genetic and molecular studies and the current diagnostic approach to this group of patients.


RESULTS
Publications over the past 5 years describe a number of new clinical phenotypes and genetic loci and further emphasize the overlap in clinical phenotype between a number of these disorders and between the distal and limb girdle myopathies and hereditary inclusion body myopathies. Recent studies have led to the identification of the genes and mutations responsible for early onset (Laing) myopathy and tibial (Udd) myopathy, and for distal myopathy with rimmed vacuoles (Nonaka), which has been shown to be allelic with quadriceps sparing hereditary inclusion body myopathy (IBM2), and have elucidated the underlying pathogenetic mechanisms in these conditions. New diagnostic approaches using magnetic resonance imaging, and a blood-based assay for dysferlin deficiency, have also been reported.


CONCLUSIONS
These findings have important implications for future genetic linkage and gene expression studies and for the diagnostic approach to patients with a distal myopathy phenotype. They also hold promise for the eventual development of therapies for this group of disorders.
Mastaglia
Frank L
FL
Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia, Australia. flmast@cyllene.uwa.edu.au
Lamont
Phillipa J
PJ
Laing
Nigel G
NG
D049310:Distal Myopathies / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D000073939:Dysferlin; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000172:deficiency; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D009154:Mutation / Q000235:genetics
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins