Undiagnosed Genetic Muscle Disease in the North of England: an in Depth Phenotype Analysis

Advances in the molecular characterisation of genetic muscle disease has been rapid, as demonstrated by a recent analysis of these conditions in the north of England by Norwood et al (2009), in which a genetic diagnosis was achieved for 75.7% of patients. However, there remain many patients with suspected genetic muscle disease in who a diagnosis is not obtained, often despite considerable diagnostic effort, and these patients are now being considered for the application of new technologies such as next generation sequencing. This study aimed to provide an in-depth phenotype analysis of undiagnosed patients referred to the Northern region muscle clinic with suspected genetic muscle disease, with the intention of gaining insight into these conditions, identifing cases with a shared phenotype who may be amenable to collective diagnostic testing or research, and evaluating the strengths and limitations of our current diagnostic strategy. We used two approaches: a review of clinical findings in patients with undiagnosed muscle disease, and a hierarchical cluster analysis to provide an unbiased interpretation of the phenotype data. These joint approaches identified a correlation of phenotypic features according to the age of disease onset and also delineated several interesting groups of patients, as well as highlighting areas of frequent diagnostic difficulty that could benefit from the use of new high-throughput diagnostic techniques. Correspondence to: anna.sarkozy@ncl.ac.uk