Lamin A/C cardiomyopathy: Young onset, high penetrance, and frequent need for heart transplantation
Hasselberg NE, Håland TF, Saberniak J, Brekke PH, Berge KE, Leren TP, Edvardsen T, Haugaa KH
Lamin A/C mutation causes dilated cardiomyopathy associated with life-threatening ventricular arrhythmias and development of severe heart failure. Sudden cardiac death can occur at a young age, but risk factors for serious events have so far been poorly defined. Furthermore, the natural course of disease in family members diagnosed by genetic screening and testing has not previously been systematically studied.
This studied was conducted to give a better overview of the prevalence and penetrance of disease as well as risk factors of serious events in lamin A/C genotype positive probands and family members.
The prevalence of Lamin A/C gene mutations was 6.2% among those referred to genetic testing with a phenotype of familial dilated cardiomyopathy in Norway from 2003 to 2015. Conduction disorder was a strong predictor of life-threatening ventricular arrhythmias, whereas reduced myocardial function by ejection fraction was the strongest predictor of death and heart transplantation (Figure). Using Oslo University’s cardiac transplant register, the study provided novel data showing that cardiac transplantation is more frequent in lamin A/C disease than in other forms of dilated cardiomyopathy and underlines the serious course of lamin A/C cardiomyopathy.
The asymptomatic lamin A/C genotype positive family members identified by genetic family screening showed a 9% annual incidence of newly documented cardiac phenotype and a 61% cardiac penetrance during follow-up.
These novel findings are of great importance for follow-up, treatment and screening for lamin A/C disease. The study highlights the importance of early family screening for lamin A/C disease by providing documentation that family members must have regular cardiological follow-up from early age to initiate treatment to avoid sudden death and progressive heart failure.
