Update 2011: clinical and genetic issues in familial dilated cardiomyopathy

Abstract

A great deal of progress has recently been made in the discovery and understanding of the genetics of familial dilated cardiomyopathy (FDC). A consensus has emerged that with a new diagnosis of idiopathic dilated cardiomyopathy (IDC), the clinical screening of first-degree family members will reveal FDC in at least 20% to 35% of those family members. Point mutations in 31 autosomal and 2 X-linked genes representing diverse gene ontogeny have been implicated in causing FDC but account for only 30% to 35% of genetic causes. Next-generation sequencing methods have dramatically decreased sequencing costs, making clinical genetic testing feasible for extensive panels of dilated cardiomyopathy genes. Next-generation sequencing also provides opportunities to discover additional genetic causes of FDC and IDC. Guidelines for evaluation and testing of FDC and IDC are now available, and when combined with FDC genetic testing and counseling, will bring FDC/IDC genetics to the forefront of cardiovascular genetic medicine.

Figure 1. Flow diagram of genetic risk assessment for patients newly diagnosed with idiopathic dilated cardiomyopathy (IDC) or familial dilated cardiomyopathy (FDC)

The left- and right-sided boxes provide guidance for negative or positive results, respectively, based on the results of history or testing recommended in the central boxes. *Always search for history or exam findings consistent with syndromic disease, particularly skeletal muscle symptoms. However, with any suggestion of syndromic disease in the proband or family members, strongly consider referral to a geneticist or CV genetic medicine clinic with genetics collaboration. Some features of early onset conduction system disease or arrhythmia (usually from LMNA rare variants) may be particularly susceptible to genetic testing. Rare variants of unknown significance are not helpful for predictive testing.