G.P.221: Diagnostic yield for LGMD at the LHSC Muscle Clinic

Abstract

Limb girdle muscular dystrophies (LGMD) are a group of rare muscular dystrophies. The molecular and genetic characteristics of the LGMDs are continually being refined. Several authors have concluded that with appropriate work-up, the yield of arriving at a specific genetic diagnosis should be between 50% and 75%. Though specific treatment options remain unavailable, diagnosis is important in predicting complications that, if effectively managed, can prevent early morbidity and mortality. Specific diagnosis is also important for genetic counselling. A retrospective chart review was conducted on 63 patients yfollowed with a LGMD phenotype, at the LHSC Muscle Clinic between 2005 and 2013. The objectives were (1) to describe the cohort of LGMD patients, (2) to determine our diagnostic yield in a centre that does not have internal molecular diagnostic capacity, and (3) to audit the diagnostic process from a quality assurance perspective. A confirmed genetic diagnosis was arrived at in 33 patients (52%). Of these, 25 had LGMD – 18 males and 7 females; 48% had LGMD 2A and the remainder had LGMD 1B, 2B, 2I and 2L. Among the others, one had congenital centronuclear myopathy with symptom onset in her fifties; three had hereditary inclusion body myopathy; three had myofibrillar myopathy and one had Pompe's disease. The average time from symptom onset to definitive diagnosis was 15years. The average time from first clinic visit to a definitive diagnosis was 2.5years. Patients without a confirmed genetic diagnosis were more likely to have incomplete or ongoing workup. Some factors that seem to have played a role in delaying definitive diagnosis include loss to follow-up, unavailability of older muscle biopsies, and evolving availability of genetic tests such as the ANO5. The diagnostic yield in the LGMD cohort was consistent with the literature. However, our quality improvement lens identified a number of systemic and patient factorsy that influence the process of diagnosis.