1 - Serviço de Genética Médica Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
2 - GenoMed - Diagnósticos de Medicina Molecular SA
3 - Instituto Medicina Molecular -FMUL
- Poster, Congresso Português de Cardiologia 2024
Resumo: Background: Sudden cardiac arrest (SCA) at a young age can be the first manifestation of an underlying genetic disorder, namely an inheritable primary arrhythmia, a cardiomyopathy, an aortopathy or other hereditary cardiac disease (HCD). The combined prevalence of HCD can be high as 1:200 and globally represents 15-20% death causes in developed countries, affecting inparticularly males under 50 years of age. Our previous works revealed an overall 21.37% genetic diagnosis (GD) rate (N=209) from a total of 978 genetic analysis performed for confirmed or suspected HCD in our laboratory. Aim: Identify and characterise cases of SCA or sudden cardiac death (SCD) that underwent a genetic testing. Compare the GD rate of the individuals tested with direct family history of SCA/SCD with the overall GD previously obtained to further validate this variable as a relevant marker of HCD. Methods: Retrospective review of the results of genetic testing performed in both probands for SCA/ SCD or probands with suspected HCD and direct family history of SCD from 2019 until 2023 and calculation of their respectively GD rate. Results: A total of 32 genetic analyses were carried out for individuals referred for SCA or SCD. From the total of these cases, after subsequent clinical evaluation, it was identified an underlying disease in 20 cases of SCA: primary arrhythmia syndrome (6), cardiomyopathy (5) and congenital cardiopathy (1). A (likely) pathogenic variant was found in 5 samples on TPM1, DSP, DSC2, RYR2, TTN genes with a diagnostic yield of 16%. Additionally, we reviewed further 77 genetic analyses performed for individuals with suspected or confirmed HCD where there was a direct family history of SCD: 36 cases of hypertrophic cardiomyopathy, 20 dilated cardiomyopathy, 1 arrhythmogenic right ventricular cardiomyopathy, 12 unspecified cardiomyopathy, 6 primary arrhythmia syndrome, 1 familial hypercholesterolemia, and 1 coronary artery disease. A (likely) pathogenic variant was found in 21 cases, namely on MYH7 (4), MYBPC3 (4), LMNA (3), TTN (2), FBN1 (1), TPM1 (1), FHOD3 (1), TTR (1), LAMA2 (1), FLNC (1), RYR2 (1), DSP (1) genes, with a diagnostic yield of 27%. Our results revealed a higher GD rate in the cohort of individuals with a family history of SCD, validating the relevance Conclusions: This work aims to add further evidence on the utility of genetic testing on case of SCA/SCD and validate that protocols of investigation of SCA/SCD should include performing routinely genetic analysis, performed in a multidisciplinary setting. Given that many cases result of HCD only identifying an underlying genetic cause can allow patients and their relatives an adequate management and screening of at-risk relatives.