2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Two Years of Newborn Screening for Duchenne Muscular Dystrophy in North Carolina: Results from Early Check

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This document summarizes the results of a two-year newborn screening program for Duchenne muscular dystrophy (DMD) in North Carolina called Early Check. The program is a collaboration between RTI International, the North Carolina State Laboratory of Public Health, Duke University, the University of North Carolina at Chapel Hill, and Wake Forest University. <br /><br />The screening process involved using an FDA-approved test for creatine kinase-MM (CK-MM) on dried blood spots from newborns. If the initial screening result was above a certain cutoff, the sample was retested in duplicate. Newborns with at least one retest above the final cutoff were referred to follow-up. The algorithm for screening was optimized by considering factors such as birthweight, age, gestational age, sex, and other genetic conditions.<br /><br />In the two years of screening, 13,432 newborns participated in the program. The results identified two males with pathogenic variants in the DMD gene, indicating they were affected by DMD. One male was found to have an autosomal dominant pathogenic variant in CLCN1, likely affected with myotonia congenita. Additionally, nine carriers of heterozygous pathogenic or likely pathogenic variants associated with recessive conditions were identified.<br /><br />Follow-up and confirmatory testing were offered to parents of infants with positive screening results. This included total creatine kinase testing at one month of age and genomic sequencing of the DMD gene as well as other genes associated with neuromuscular conditions. A clinical research visit was also scheduled at 6-8 months of age.<br /><br />The screening program has provided valuable information about the prevalence of DMD and other genetic conditions in newborns in North Carolina. The results suggest that including genomic sequencing and repeat CK-MM or total CK testing after 72 hours of age could further improve the accuracy of the screening and detection of DMD.

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Presenting Author - Katerina S. Kucera, PhD; Co-Author - Mary Beth L. Boyea, MS; Co-Author - Brooke Migliore, BS; Co-Author - Veronica Robles, BS; Co-Author - Heidi Cope, MS, CGC; Co-Author - Catherine W. Rehder; Co-Author - Edward C. Smith, MD; Co-Author - Don Bailey, PhD; Co-Author - Holly L. Peay, PhD, MS, CGC;

Meta Tag

Biochemical genetics

Congenital Anomaly

Genetic Testing

Musculoskeletal system

Natural History

NextGen Sequencing

Sequencing

Variant Detection

Co-Author Mary Beth L. Boyea, MS

Co-Author Brooke Migliore, BS

Co-Author Veronica Robles, BS

Co-Author Heidi Cope, MS, CGC

Co-Author Catherine W. Rehder

Co-Author Edward C. Smith, MD

Co-Author Don Bailey, PhD

Co-Author Holly L. Peay, PhD, MS, CGC

Presenting Author Katerina S. Kucera, PhD

Keywords

newborn screening

Duchenne muscular dystrophy

Early Check

CK-MM

screening algorithm

genetic conditions

pathogenic variants

DMD gene

heterozygous variants

genomic sequencing