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

Overview

Journal J Neuromuscul Dis

Publisher Sage Publications

Specialty Neurology

Date 2018 Oct 16

PMID 30320597

Citations 12

Authors

Jennifer G Andrews

Molly M Lamb

Kristin Conway

Natalie Street

Christina Westfield

Emma Ciafaloni

Dennis Matthews

Christopher Cunniff

Shree Pandya

Deborah J Fox

Affiliations

Soon will be listed here.

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.

Citing Articles

Prophylactic Use of Cardiac Medications and Survival in Duchenne Muscular Dystrophy.

Conway K, Thomas S, Neyaz T, Ciafaloni E, Mann J, Staron-Ehlinger M Muscle Nerve. 2025; 71(4):574-582.

PMID: 39853770 PMC: 11887528. DOI: 10.1002/mus.28353.

Draft Guidance for Industry Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, and Related Dystrophinopathies - Developing Potential Treatments for the Entire Spectrum of Disease.

McDonald C, Camino E, Escandon R, Finkel R, Fischer R, Flanigan K J Neuromuscul Dis. 2024; 11(2):499-523.

PMID: 38363616 PMC: 10977441. DOI: 10.3233/JND-230219.

Clinical and genetic characteristics of Chinese Duchenne/Becker muscular dystrophy patients with small mutations.

Gan S, Liu S, Yang H, Wu L Front Neurosci. 2022; 16:992546.

PMID: 36419457 PMC: 9677089. DOI: 10.3389/fnins.2022.992546.

Selected clinical and demographic factors and all-cause mortality among individuals with Duchenne muscular dystrophy in the Muscular Dystrophy Surveillance, Tracking, and Research Network.

Paramsothy P, Wang Y, Cai B, Conway K, Johnson N, Pandya S Neuromuscul Disord. 2022; 32(6):468-476.

PMID: 35597713 PMC: 9214635. DOI: 10.1016/j.nmd.2022.04.008.

Study of Clinical Features and Diagnosis Pattern of Duchene Muscular Dystrophy in Southern India.

Sattenapalli N, Areti A, G S, Kulandaivelu U, Alavala R, Manne R J Neurosci Rural Pract. 2022; 13(1):43-49.

PMID: 35110919 PMC: 8803508. DOI: 10.1055/s-0041-1740614.

References

Sironi M, Pozzoli U, Cagliani R, Comi G, Bardoni A, Bresolin N . Analysis of splicing parameters in the dystrophin gene: relevance for physiological and pathogenetic splicing mechanisms. Hum Genet. 2001; 109(1):73-84. DOI: 10.1007/s004390100547. View

Muntoni F, Torelli S, Ferlini A . Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003; 2(12):731-40. DOI: 10.1016/s1474-4422(03)00585-4. View

Gangopadhyay S, Sherratt T, Heckmatt J, Dubowitz V, Miller G, Shokeir M . Dystrophin in frameshift deletion patients with Becker muscular dystrophy. Am J Hum Genet. 1992; 51(3):562-70. PMC: 1682710. View

Yilmaz O, Karaduman A, Topaloglu H . Prednisolone therapy in Duchenne muscular dystrophy prolongs ambulation and prevents scoliosis. Eur J Neurol. 2004; 11(8):541-4. DOI: 10.1111/j.1468-1331.2004.00866.x. View

Elhawary N, Nasser A E, Shawky R, Hashem N . Frameshift deletion mechanisms in Egyptian Duchenne and Becker muscular dystrophy families. Mol Cells. 2004; 18(2):141-9. View

Dent K, Dunn D, von Niederhausern A, Aoyagi A, Kerr L, Bromberg M . Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A. 2005; 134(3):295-8. DOI: 10.1002/ajmg.a.30617. View

Carsana A, Frisso G, Tremolaterra M, Lanzillo R, Vitale D, Santoro L . Analysis of dystrophin gene deletions indicates that the hinge III region of the protein correlates with disease severity. Ann Hum Genet. 2005; 69(Pt 3):253-9. DOI: 10.1046/j.1529-8817.2005.00160.x. View

Balaban B, Matthews D, Clayton G, Carry T . Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: long-term effect. Am J Phys Med Rehabil. 2005; 84(11):843-50. DOI: 10.1097/01.phm.0000184156.98671.d0. View

Gualandi F, Rimessi P, Trabanelli C, Spitali P, Neri M, Patarnello T . Intronic breakpoint definition and transcription analysis in DMD/BMD patients with deletion/duplication at the 5' mutation hot spot of the dystrophin gene. Gene. 2006; 370:26-33. DOI: 10.1016/j.gene.2005.11.002. View

10.

Biggar W, Harris V, Eliasoph L, Alman B . Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006; 16(4):249-55. DOI: 10.1016/j.nmd.2006.01.010. View

11.

Aartsma-Rus A, van Deutekom J, Fokkema I, van Ommen G, den Dunnen J . Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve. 2006; 34(2):135-44. DOI: 10.1002/mus.20586. View

12.

Miller L, Romitti P, Cunniff C, Druschel C, Mathews K, Meaney F . The muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): surveillance methodology. Birth Defects Res A Clin Mol Teratol. 2006; 76(11):793-7. PMC: 5863910. DOI: 10.1002/bdra.20279. View

13.

King W, Ruttencutter R, Nagaraja H, Matkovic V, Landoll J, Hoyle C . Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology. 2007; 68(19):1607-13. DOI: 10.1212/01.wnl.0000260974.41514.83. View

14.

Houde S, Filiatrault M, Fournier A, Dube J, Darcy S, Berube D . Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol. 2008; 38(3):200-6. DOI: 10.1016/j.pediatrneurol.2007.11.001. View

15.

Kesari A, Pirra L, Bremadesam L, McIntyre O, Gordon E, Dubrovsky A . Integrated DNA, cDNA, and protein studies in Becker muscular dystrophy show high exception to the reading frame rule. Hum Mutat. 2008; 29(5):728-37. DOI: 10.1002/humu.20722. View

16.

Dastur R, Gaitonde P, Khadilkar S, Nadkarni J . Becker muscular dystrophy in Indian patients: analysis of dystrophin gene deletion patterns. Neurol India. 2008; 56(3):374-8. DOI: 10.4103/0028-3886.40961. View

17.

Desguerre I, Christov C, Mayer M, Zeller R, Becane H, Bastuji-Garin S . Clinical heterogeneity of duchenne muscular dystrophy (DMD): definition of sub-phenotypes and predictive criteria by long-term follow-up. PLoS One. 2009; 4(2):e4347. PMC: 2633042. DOI: 10.1371/journal.pone.0004347. View

18.

Straathof C, Overweg-Plandsoen W, van den Burg G, van der Kooi A, Verschuuren J, de Groot I . Prednisone 10 days on/10 days off in patients with Duchenne muscular dystrophy. J Neurol. 2009; 256(5):768-73. DOI: 10.1007/s00415-009-5012-y. View

19.

Tuffery-Giraud S, Beroud C, Leturcq F, Ben Yaou R, Hamroun D, Michel-Calemard L . Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Hum Mutat. 2009; 30(6):934-45. DOI: 10.1002/humu.20976. View

20.

Desguerre I, Mayer M, Christov C, Leturcq F, Chelly J, Gherardi R . [Phenotypic heterogeneity of Duchenne myopathy and prognosis criteria]. Arch Pediatr. 2009; 16(6):681-3. DOI: 10.1016/S0929-693X(09)74110-7. View