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

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.

Pilot study of population-based newborn screening for spinal muscular atrophy in New York state.

PurposeTo determine feasibility and utility of newborn screening for spinal muscular atrophy (SMA) in New York State.MethodsWe validated a multiplex TaqMan real-time quantitative polymerase chain reaction assay using dried blood spots for SMA. From January 2016 to January 2017, we offered, consented, and screened 3,826 newborns at three hospitals in New York City and tested newborns for the deletion in exon 7 of SMN1.ResultsNinety-three percent of parents opted in for SMA screening. Overall the SMA carrier frequency was 1.5%. We identified one newborn with a homozygous SMN1 deletion and two copies of SMN2, which strongly suggests the severe type 1 SMA phenotype. The infant was enrolled in the NURTURE clinical trial and was first treated with Spinraza at age 15 days. She is now age 12 months, meeting all developmental milestones, and free of any respiratory issues.ConclusionOur pilot study demonstrates the feasibility of population-based screening, the acceptance by families, and the benefit of newborn screening for SMA. We suggest that SMA be considered for addition to the national recommended uniform screening panel.

Psychological stress associated with cardiogenetic conditions.

AIM: Genetic testing now makes it possible to identify specific mutations that may lead to life-threatening cardiac arrhythmias. This article presents data from a qualitative research study that explored the subjective experiences of individuals and families with cardiogenetic conditions. We focus on describing patients' experiences of psychological stresses associated with having a cardiogenetic condition, illustrating the importance of integrating psychological and medical care. This integration of care is particularly important as personalized genomic medicine continues to evolve and the implications of genetic testing have a profound effect on individuals and families. METHODS: The researchers interviewed 50 participants from 32 families. The research team used a systematic, grounded theory procedure to code and analyze interview and focus group transcripts, incorporating multiple coders at several stages of the data analysis process. RESULTS: Three major themes emerged: a bereavement trajectory associated with sudden death in the absence of prior symptoms; high anxiety about transmitting a genetic mutation; and resilience reflected in positive lifestyle changes and participation in support groups. CONCLUSION: This article identifies patient perspectives on personalized genomic medicine in cardiogenetics that can improve clinical care, including: specialized bereavement counseling; improving education about cardiogenetic conditions for medical professionals; parent guidelines for discussing cardiogenetic conditions with their children; information about support groups; and the routine inclusion of clinical psychologists in interdisciplinary treatment teams. Given recent advances in technology and decreasing costs, whole-genome sequencing is likely to become common practice in the near future. Therefore, these recommendations are likely to be relevant for other genetic conditions, as well as the entire field of personalized genomic medicine.

Translating advances in cardiogenetics into effective clinical practice.

In this article we describe a qualitative research study in which we explored individuals' subjective experiences of both genetic testing and cardiogenetic disorders. Using a grounded theory approach, we coded and analyzed interview and focus group transcripts from 50 participants. We found that just under half of the participants who received their diagnosis during the study reported difficulty understanding information about both the purpose of genetic testing and their cardiac disease. A high level of anxiety about genetic testing and cardiac symptoms exacerbated individuals' cognitive confusion. Participants reported both positive and negative interactions with the medical community, depending on health care professionals' knowledge of cardiogenetic disorders. Overall, participants expressed a range of attitudes--positive, negative, and ambivalent--toward genetic testing. We conclude with a discussion of the barriers to achieving effective clinical care for genetic conditions and offer suggestions for improving collaborative decision making between physicians and patients.