The role of post mortem genetic testing and family screening of young sudden cardiac death cases

Sudden unexplained death in a young (<40 years) may be the first manifestation of an unknown inherited cardiac disease. Establishing the cause of sudden cardiac death (SCD) is important as it permits the pre symptomatic identification of relatives at risk of SCD. Establishing the diagnosis is challenging, as in many cases there are negative autopsy findings and thus post mortem genetic testing and family screening are the only possible modalities.

The aim of our study was to evaluate the yield of post mortem genetic testing and family screening in reaching the final diagnosis.

Among families with SCD as first manifestation who were referred to our inherited arrhythmia clinic during 2012-2023 in 22 cases DNA of the proband was available. Our protocol included consistent genetic panel of 343 genes linked to cardiomyopathy, channelopathy, cardiovascular disease and SCD and thorough clinical evaluation of first-degree relatives.

Twenty-two index cases, 19 ±11 years and 135 family members were studied. Genetic diagnosis was established in 12 cases (55%) and supported the diagnosis of long QT in 6 cases, CPVT in 5 cases and SSS in one case. Clinical evaluation in these 12 families strengthened the diagnosis in eight families and revealed 39 (29%) affected family members. All the affected family members carried the genetic variant found in the proband and were medically treated. In 2/12 families clinical and genetic evaluation of family members was negative. Positive post mortem genetic testing was associated with younger age (15 ±8 vs 26 ±11, p=0.02) and clinically affected family members (67% vs 10% p=0.007).

Our study supports the inclusion of post mortem genetic testing and family screening in routine protocols of young SCD cases, especially in children and when other family members are suspected to be clinically effected.