TY - JOUR
T1 - Diagnostic accuracy of phenotype classification in duchenne and becker muscular dystrophy using medical record data
AU - Andrews, Jennifer G.
AU - Lamb, Molly M.
AU - Conway, Kristin
AU - Street, Natalie
AU - Westfield, Christina
AU - Ciafaloni, Emma
AU - Matthews, Dennis
AU - Cunniff, Christopher M
AU - Pandya, Shree
AU - Fox, Deborah J.
N1 - Funding Information:
Our study demonstrates the feasibility of distinguishing among dystrophinopathy phenotypes by using three empirically defined indices amid variability in clinical presentation. When the phenotypes assigned according to each of the three indices–mobility status, molecular test results, and onset of symptoms–are concordant, confidence in the This publication was supported by the grant numbers, DD000830, DD000831, DD000832, DD000834, DD000835, DD000836, DD000837 funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Diseases Control and Prevention or the Department of Health and Human Services. Research was performed in compliance with guidelines on human subjects research either through local Institutional Review Board approvals or exemptions as public health related activities.
Publisher Copyright:
© 2018 - IOS Press and the authors. All rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Becker
KW - Duchenne
KW - Muscular dystrophies
KW - diagnostic accuracy
KW - dystrophinopathy
KW - phenotype
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UR - http://www.scopus.com/inward/citedby.url?scp=85055618102&partnerID=8YFLogxK
U2 - 10.3233/JND-180306
DO - 10.3233/JND-180306
M3 - Article
C2 - 30320597
AN - SCOPUS:85055618102
VL - 5
SP - 481
EP - 495
JO - Journal of Neuromuscular Diseases
JF - Journal of Neuromuscular Diseases
SN - 2214-3599
IS - 4
ER -