Cardiac conduction disorders in young adults: Clinical characteristics and genetic background of an underestimated population

Abstract

Background: Cardiac conduction disorder (CCD) in patients <50 years old is a rare and mostly unknown condition.

Objective: We aimed to assess clinical characteristics and genetic background of patients <50 years old with CCD of unknown origin.

Methods: We retrospectively reviewed a consecutive series of patients with a diagnosis of CCD before the age of 50 years referred to our center between January 2019 and December 2021. Patients underwent complete clinical examination and genetic evaluation.

Results: We enrolled 39 patients with a median age of 40 years (28-47 years) at the onset of symptoms. A cardiac implantable electronic device was implanted in 69% of the patients. In 15 of 39 CCD index patients (38%), we found a total of 13 different gene variations (3 pathogenic, 6 likely pathogenic, and 4 variants of uncertain significance), mostly in 3 genes (SCN5A, TRPM4, and LMNA). In our cohort, genetic testing led to the decision to implant an implantable cardioverter-defibrillator in 2 patients for the increased risk of sudden cardiac death.

Conclusion: Patients with the occurrence of CCD before the age of 50 years present with a high rate of pathologic gene variations, mostly in 3 genes (SCN5A, TRPM4, and LMNA). The presence of pathogenic variations may add information about the prognosis and lead to an individualized therapeutic approach.

Keywords: Atrioventricular block; Cardiac conduction disorders; Gene variants; Pacemaker; Young.