Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy

• Main Authors: Marey Isabelle, Fressart Véronique, Rambaud Caroline, Fornes Paul, Martin Laurent, Grotto Sarah, Alembik Yves, Gorka Hervé, Millat Gilles, Gandjbakhch Estelle, Bordet Céline, Grandmaison Geoffroy Lorin de la, Richard Pascale, Charron Philippe
• Format: Article
• Language: English
• Published: De Gruyter 2020-05-01
• Series: Open Medicine
• Subjects: sudden death; cardiac death; cardiomyopathy; post-mortem; genetic testing
• Online Access: https://doi.org/10.1515/med-2020-0150

Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.