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

Abstract

ObjectiveDuchenne 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.MethodsAt 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.ResultsIn 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.InterpretationThis 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.

Age-Related Blood Levels of Creatine Kinase-MM in Newborns and Patients with Duchenne Muscular Dystrophy: Considerations for the Development of Newborn Screening Algorithms

“…Conversely, the rapid stabilization of blood CK-MM in healthy newborns can be readily detected with repeat testing within a few days after birth. Repeat specimens were not available from newborns with DMD for comparison; however, given the sustained CK-MM elevation in older children, and previously reported cases of repeat testing in newborns with neuromuscular conditions [10,14,21], repeat CK-MM testing is expected to The midpoint between 0 and 29.2 ng/mL (14.6 ng/mL) was used for values below the lower limit of the reportable range of the assay (<29.2 ng/mL). Values above the upper limit of the reportable range (>8000 ng/mL) are included but not considered quantitative.…”

“…1 Hartnett et al (2022)-[12] Maloney et al (2023)-[17] Park et al (2022)-[20] Tavakoli et al (2023)-[21] …”

Assessing the Benefits and Harms Associated with Early Diagnosis from the Perspective of Parents with Multiple Children Diagnosed with Duchenne Muscular Dystrophy

“…Despite potential benefits of NBS, the implementation of DMD NBS is limited in the US. Notably, New York [ 15 ], Minnesota [ 16 ], and Ohio [ 17 ] plan to have universal screening in 2024, with three pilot studies recently concluded or underway in New York [ 18 ], North Carolina [ 19 ], and in Boston, Massachusetts [ 20 ] to support the inclusion of DMD on the Recommended Uniform Screening Panel (RUSP).…”

Gait Characterization in Duchenne Muscular Dystrophy (DMD) Using a Single-Sensor Accelerometer: Classical Machine Learning and Deep Learning Approaches

“…DMD is the result of mutations in the DMD gene and subsequent changes in the dystrophin protein in skeletal and smooth muscle, the brain, and other organs, leading to progressive loss of muscle strength and mobility and a nonprogressive but variable behavioral phenotype that can include intellectual disability and autism-like features [ 4 , 5 , 6 ]. DMD is present from birth but early detection through pilot newborn screening programs is becoming increasingly common [ 7 ]. At the same time, multiple new therapies for DMD have achieved market approval with more in the development process, providing clinicians with potential options for early intervention [ 8 ].…”