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. 2023 Aug;10(8):1383-1396.
doi: 10.1002/acn3.51829. Epub 2023 Jun 23.

Newborn screening for Duchenne muscular dystrophy: A two-year pilot study

Norma P Tavakoli  1   2 , Dorota Gruber  3   4 , Niki Armstrong  5 , Wendy K Chung  6 , Breanne Maloney  1 , Sunju Park  1 , Julia Wynn  6 , Carrie Koval-Burt  6 , Lorraine Verdade  3 , David H Tegay  3   7 , Lilian L Cohen  8 , Natasha Shapiro  9 , Annie Kennedy  10 , Garey Noritz  11 , Emma Ciafaloni  12 , Barry Weinberger  13   14 , Marty Ellington Jr  14   15 , Charles Schleien  3   14 , Regina Spinazzola  14   16 , Sunil Sood  14   17 , Amy Brower  18 , Michele Lloyd-Puryear  19 , Michele Caggana  1   2 ; Duchenne Muscular Dystrophy Pilot Study Group
Collaborators, Affiliations

Newborn screening for Duchenne muscular dystrophy: A two-year pilot study

Norma P Tavakoli et al. Ann Clin Transl Neurol. 2023 Aug.

Abstract

Objective: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis.

Methods: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene.

Results: In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified.

Interpretation: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.

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Conflict of interest statement

W.K.C. is on the Board of Directors of Prime Medicine. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Duchenne muscular dystrophy testing algorithm. CK‐MM, creatine kinase‐MM; DBS, dried blood spot; AOC, age of collection; SCC, specialty care center; NGS, next‐generation sequencing; DMD, Duchenne muscular dystrophy; NM, neuromuscular. *Note that several methods, and gene panels were used based on which laboratory performed the genetic testing (supplementary material). Shading indicates actions performed at specialty care center.
Figure 2
Figure 2
Outcome of screening for Duchenne muscular dystrophy. DMD, Duchenne muscular dystrophy; BMD, Becker muscular dystrophy.
Figure 3
Figure 3
Potential Duchenne muscular dystrophy screening algorithm. NBS, newborn screening; CK‐MM, creatine kinase‐MM; DBS, dried blood spot; DMD, Duchenne muscular dystrophy; PCP, primary care physician; HOB, hospital of birth; PV/LPV, pathogenic variant/likely pathogenic variant; SCC, specialty care center. Shading indicates actions performed at specialty care center.
See this image and copyright information in PMC

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