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Genetic screening of relatives of decedents experiencing sudden unexpected death: medical examiner’s office referrals to a multi-disciplinary cardiogenetics program

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Abstract

Currently, no standardized system exists for evaluating and testing at-risk family members of decedents with abnormal post-mortem genetic testing in cases of sudden unexpected death (SUD). The goal of this study was to evaluate the outcomes of referrals made by an urban medical examiner’s office to a multi-disciplinary cardiogenetics clinic. Relatives of decedents with pathogenic/likely pathogenic (P/LP) variants or variants of unknown significance (VUS) in genes known to be associated with cardiomyopathies and/or arrhythmias were identified by the New York City Office of Chief Medical Examiner and referred to the Cardiogenetics Clinic at Montefiore Medical Center. Familial referrals of 15 decedents (median 15 years, range 2 days to 57 years) were evaluated. Variants in 13 genes were identified among decedents (9 arrhythmia, 5 cardiomyopathy). P/LP variants were identified in both arrhythmia (RYR2, SCN5A) and cardiomyopathy syndrome (MYBPC3 (2), MYH7) genes. Thirty-two family members were referred, and 14 variants were detected. One pathogenic (MYBPC3) and two likely pathogenic (RYR2, MYH7) mutations were identified. Referral of at-risk family members of decedents who experienced SUD based on informative post-mortem genetic testing for cardiac and genetic evaluation is warranted, as family studies help to reclassify variants and prevent additional sudden death.

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Authors and Affiliations

  1. Department of Pediatrics, Children’s Hospital at Montefiore, Bronx, New York, NY, USA

    Tamar Siskind

  2. New York City Office of Chief Medical Examiner, New York, NY, USA

    Nori Williams, Barbara Sampson & Yingying Tang

  3. Division of Genetics, Children’s Hospital at Montefiore, Bronx, New York, NY, USA

    Monisha Sebastin & Robert Marion

  4. Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, NY, USA

    Robert Marion & Bradley C. Clark

  5. Division of Cardiology, Albert Einstein College of Medicine, Bronx, New York, NY, USA

    Thomas V. McDonald

  6. Division of Cardiology, Children’s Hospital at Montefiore, Bronx, New York, NY, USA

    Christine Walsh & Bradley C. Clark

Authors
  1. Tamar Siskind
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  2. Nori Williams
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  4. Robert Marion
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  5. Thomas V. McDonald
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  7. Barbara Sampson
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  8. Yingying Tang
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  9. Bradley C. Clark
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Contributions

TS: data collection and analysis, first draft of the manuscript.

NW, BS, YT: assistance with patient identification, data analysis.

MS, RB, TM, CW: data collection and analysis, final approval of the manuscript.

BC: data analysis, revision of the manuscript, senior author.

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Correspondence to Bradley C. Clark.

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Siskind, T., Williams, N., Sebastin, M. et al. Genetic screening of relatives of decedents experiencing sudden unexpected death: medical examiner’s office referrals to a multi-disciplinary cardiogenetics program. J Community Genet 13, 629–639 (2022). https://doi.org/10.1007/s12687-022-00611-1

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