Population-based genetic epidemiology of selected muscular dystrophies: the Muscular Dystrophy Surveillance, Tracking and Research Network (MDSTARnet)


Clinical Management

Poster Number: 33


Peter Kang, MD, Paul and Sheila Wellstone Muscular Dystrophy Center and Dept of Neurology, U of MN Medical School, Magali Jorand-Fletcher, MPH, University of Florida College of Medicine, Wanfang Zhang, University of South Carolina, Suzanne McDermott, City University of New York, Reba Berry, South Carolina Department of Health, Chelsea Chambers, MS, CGC, Virginia Commonwealth University, Kristen Wong, University of Utah, Kristin Conway, PhD, University of Iowa, Yara Mohamed, MD, University of Florida College of Medicine, Shiny Thomas, New York State Department of Health, Albany, NY, Yedatore Venkatesh, MD, University of South Carolina School of Medicine, Columbia, SC, Christina Westfield, New York State Department of Health, Albany, NY, Nedra Whitehead, MS, PhD, RTI International, Research Triangle Park, NC, Nicholas Johnson, MD, Virginia Commonwealth University

Background: We intended to characterize population-based epidemiologic patterns of genetic findings in Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), and distal muscular dystrophy (DD) in selected areas of the United States. Methods: Individuals who were clinically diagnosed with and received care for one of these muscular dystrophies from 1/1/2008 through 12/31/2016, within the area covered by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) were examined for certainty of diagnosis, demographics, and genetic test findings. Variants of unknown significance (VUS) were re-analyzed for changes in interpretation since the original test report. Results: We ascertained 243 individuals whose diagnoses met criteria for definite or probable muscular dystrophy. LGMD was the most common diagnosis (138 cases), followed by CMD (62 cases). EDMD and DD were rare (21 and 22 cases, respectively). Among the demographic data, the most striking finding was a skewed gender ratio favoring males. Even after excluding X-linked genes (EMD) and autosomal genes reported to have skewed gender ratios (ANO5, CAV3, and LMNA), the cohort was 57% male. The most common associated genes were FKRP, CAPN3, ANO5, and DYSF. Overall, 51 VUSs were resolved to more definitive variant interpretations on re-analysis. Discussion: This study is distinct for being a population-based examination of several types of muscular dystrophies in selected areas of the United States. The gender distribution raises concerns about potential barriers to diagnosis and care for females with muscular dystrophy. The frequency of muscular dystrophy categories and associated genes are in line with other studies. Given the number of VUSs that were resolved upon re-analysis, our findings suggest that periodic re-examination of genetic test reports is worthwhile. Such re-examinations promise to resolve some genetic diagnostic ambiguities before initiating repeat testing or more invasive diagnostic procedures such as muscle biopsy.