Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• Lamin A/C (LMNA) mutations are a known cause of familial dilated cardiomyopathy (DCM).
• These mutations are associated with conduction blocks and arrhythmias.
• Understanding their prevalence and impact in specific populations is important for clinical management.

Purpose of the Study:

• To determine the prevalence of LMNA mutations in familial DCM patients in Norway.
• To assess the cardiac penetrance and expressivity of these mutations.
• To identify risk factors and outcomes for patients with LMNA mutations.

Main Methods:

• Genetic testing was performed on familial DCM probands and their relatives.
• Clinical evaluation included ECG, Holter monitoring, cardiac MRI, and echocardiography.
• Cardiac phenotype was defined by AV block, AF/flutter, VT, or echocardiographic DCM.

Main Results:

• LMNA mutations were identified in 6.2% of familial DCM probands (35/561).
• Family screening identified an additional 93 LMNA genotype-positive individuals.
• Asymptomatic family members showed a 9% annual incidence of cardiac phenotype and 61% penetrance over 4.4 years, with high rates of AV block and VT.

Conclusions:

• LMNA mutations account for a significant proportion of familial DCM in Norway.
• Early family screening and cardiological follow-up are vital for detecting cardiac phenotypes, including AV block and VT.
• Approximately 19% of LMNA patients required heart transplantation, underscoring disease severity.