American College of Medical Genetics

This cross-sectional study describes the collection and use of state-provided data on newborn screening for spinal muscular atrophy.

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.

Recent advancements in gene-targeted therapies have highlighted the critical role data sharing plays in successful translational drug development for people with rare diseases. To scale these efforts, we need to systematize these sharing principles, creating opportunities for more rapid, efficient, and scalable drug discovery/testing including long-term and transparent assessment of clinical safety and efficacy. A number of challenges will need to be addressed, including the logistical difficulties of studying rare diseases affecting individuals who may be scattered across the globe, scientific, technical, regulatory, and ethical complexities of data collection, and harmonization and integration across multiple platforms and contexts. The NCATS/NIH Gene-Targeted Therapies: Early Diagnosis and Equitable Delivery meeting series held during June 2021 included data sharing models that address these issues and framed discussions of areas that require improvement. This article describes these discussions and provides a series of considerations for future data sharing.