Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

I A W van Rijsingen; J F Hermans-van Ast; Y H J M Arens; S M Schalla; C E M de Die-Smulders; A van den Wijngaard; Y M Pinto

doi:10.1007/BF03086304

Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

Neth Heart J. 2009 Dec;17(12):458-63. doi: 10.1007/BF03086304.

Authors

I A W van Rijsingen¹, J F Hermans-van Ast, Y H J M Arens, S M Schalla, C E M de Die-Smulders, A van den Wijngaard, Y M Pinto

Affiliation

¹ Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.

Abstract

Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.Methods and results. We describe a family in which members carry either a single mutation or are double heterozygous for mutations in myosin heavy chain gene (MYH7) and cysteine and glycine-rich protein 3 (CSRP3). The described family emphasises the idea of a more severe clinical phenotype with double-heterozygous mutations. It also highlights the importance of cardiological screening where NT-proBNP may serve as an added diagnostic tool.Conclusion. With a more severe inexplicable phenotype of HCM within a family, one should consider the possibility of double-heterozygous mutations. This implies that in such families, even when one disease-causing mutation is found, all the family members still have an implication for cardiological screening parallel to extended genetic screening. (Neth Heart J 2009;17:458-63.).

Keywords: cardiomyopathy; double-heterozygous mutations; genetics; hypertrophic; proBNP.