Diagnostic Accuracy of Phenotype Classification in Duchenne and Becker Muscular Dystrophy Using Medical Record Data¹

Article type: Research Article

Authors: Andrews, Jennifer G.^{a; *} | Lamb, Molly M.^b | Conway, Kristin^c | Street, Natalie^d | Westfield, Christina^e | Ciafaloni, Emma^f | Matthews, Dennis^g | Cunniff, Christopher^h | Pandya, Shree^f | Fox, Deborah J.^e | MD STARnetⁱ

Affiliations: [a] Department of Pediatrics, University of Arizona, Tucson, Arizona, USA | [b] Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA | [c] Department of Epidemiology, The University of Iowa, Iowa City, Iowa, USA | [d] National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA | [e] New York State Department of Health, Albany, New York, USA | [f] Department of Neurology, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, New York, USA | [g] Physical Medicine and Rehabilitation, School of Medicine, University of Colorado, Aurora, Colorado, USA | [h] Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA

Correspondence: [*] Correspondence to: Jennifer G. Andrews, Department of Pediatrics, University of Arizona, PO Box 245073, Tucson, AZ 85724-5073, USA.Tel.: +1 520 626 6816; Fax: +1 520 626 8056; E-mail: [email protected].

Note: [1] The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Abstract: Dystrophinopathies are caused by mutations in DMD resulting in progressive muscle weakness. They are historically divided into the more severe Duchenne (DMD) and milder Becker (BMD) muscular dystrophy phenotypes. Classification is important for research and clinical care. The purpose of this study was to describe a multi-variable approach to classifying cases from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) and to assess the accuracy of the diagnostic classification scheme. We used age at loss of mobility, molecular testing results, and age at symptom onset to classify cases as having DMD or BMD and to assess sensitivity and specificity. Mobility status showed low sensitivity and high specificity for predicting DMD (65.5% and 99.3%, respectively) and BMD (62.8% and 97.7%, respectively) phenotypes. Molecular testing showed 90.9% sensitivity and 66.4% specificity for DMD; 76.3% sensitivity and 90.0% specificity for BMD. Age of onset predicted DMD with sensitivity of 73.9% and specificity of 69.0%; BMD had 99.7% specificity and 36.7% sensitivity. Mobility status, molecular test results, and age at symptom onset are important but inconsistent measures for accurately classifying individuals into DMD or BMD phenotypes. These results have implications for prognosis in newly diagnosed individuals and for classifying phenotype in clinical trials.

Keywords: Muscular dystrophies, Duchenne, Becker, phenotype, diagnostic accuracy, dystrophinopathy

DOI: 10.3233/JND-180306

Journal: Journal of Neuromuscular Diseases, vol. 5, no. 4, pp. 481-495, 2018