High prevalence and distinctive clinical features of LMNA-associated atrioventricular block in young patients

Area of Science:

• Cardiovascular Genetics
• Medical Genetics
• Molecular Cardiology

Background:

• Atrioventricular block (AVB) is typically a degenerative condition affecting older individuals.
• In younger patients, AVB is uncommon and often lacks a clear etiological explanation.
• Investigating genetic factors is crucial for understanding AVB in young populations.

Purpose of the Study:

• To explore the role of genetic variations in the etiology of unexplained atrioventricular block (AVB) in young patients.
• To identify specific genetic variants associated with AVB in this demographic.
• To correlate genetic findings with clinical and phenotypic characteristics.

Main Methods:

• A cohort of 41 patients under 55 years old with high-degree AVB of unknown etiology was recruited.
• Clinical data and genetic information were systematically collected from all participants.
• Genetic variants were identified using molecular genetic techniques.

Main Results:

• Genetic variants were detected in 48.8% of the young AVB patients.
• LMNA variants were identified in 55% of genotype-positive patients, including pathogenic, likely pathogenic, and uncertain significance variants.
• Patients with LMNA variants exhibited a later age of AVB onset, increased family history of cardiac events, higher prevalence of atrial and ventricular arrhythmias, and cardiac chamber enlargement.

Conclusions:

• Genetic variations, especially LMNA variants, are a predominant cause of AVB in young patients.
• LMNA variants are associated with a distinct clinical phenotype in affected individuals.
• These findings contribute to understanding the genetic underpinnings of AVB in younger populations.