In response to the comment by Limeres Freire et al.1 regarding the article published recently in Revista Española de Cardiología, we would like to clarify some points.
The hypertrophic cardiomyopathy phenotype is variable for carriers of the same founder mutation2 and even for identical twins who are carriers. External factors related to lifestyle and other diseases such as hypertension or physical activity may also have an impact on development of hypertrophic cardiomyopathy.
One of the study limitations is the analysis of the possible impact of double mutations. The prevalence of double mutations would explain variations in a small number of patients (5%-10%).3
Other genetic factors such as polymorphisms in genes associated with the renin-angiotensin-aldosterone system could enhance the development of hypertrophy in carriers of mutations in sarcomeric genes.4 Study of these variants has shown certain discrepancies, and so inclusion in the present study, although of interest, would have complicated interpretation of the analysis and make it difficult to draw conclusions.
There have been reports of other genes, such as FHL1, which rarely cause hypertrophic cardiomyopathy alone, which may explain the different expression between men and women.5
Other epigenetic factors such as methylation or the involvement of microRNA could modulate phenotype expression. However, studies of this type are complex and require cardiac tissue samples, which are not available to us.
The results of our study on the impact of sex, hypertension, and physician activity in phenotype expression in the broad sense should be confirmed in other patient populations with hypertrophic cardiomyopathy.
.