Integrating current knowledge for common forms of heart failureClinical Screening and Genetic Testing
Section snippets
HCM
The genetic architecture of hypertrophic cardiomyopathy (Table 1) makes it amenable to genetic diagnosis. HCM appears to be familial in approximately 50% of cases and the inheritance pattern in documented cases is almost always autosomal dominant with high penetrance.1, 2 There are 12 known genes responsible for this disorder (not including several phenotypic mimics),3 and mutations in the exons or splice junctions of one of eight sarcomeric genes explain approximately 50% to 60% of cases.4
DCM
DCM is considerably more complex than HCM, both in terms of genetic architecture and known contributing environmental factors. Coronary artery disease, nutritional deficiency, viral infection, and toxins such as alcohol can cause DCM, though familial predisposition may continue to play a role in many of these cases. The prevalence of DCM may be as high as 1 in 2500 adults.9 Given that the histologic findings of DCM are nonspecific with myocyte loss and interstitial fibrosis, a diagnosis of
ARVD
ARVD is a genetically heterogeneous disorder, with 12 current genetic loci (ARVD1-12) identified through linkage studies (see Table 1).17 Causal genes corresponding to eight of these loci have been found, with five encoding desmosomal proteins. The prevalence of ARVD is unknown but has been estimated at 1:1000 to 1:5000 individuals.18 ARVD is familial in nearly 50% of cases19 and inheritance is usually autosomal dominant, with variable expressivity and incomplete penetrance.
The routine
RCM
RCMs demonstrate several rare hereditary variants, including familial idiopathic restrictive cardiomyopathy and hereditary amyloidosis. Familial idiopathic RCM is extremely rare, with reports only in small case series.34, 35 No gene has yet been identified. Furthermore, in some families with HCM, individual members can show a pattern of restrictive filling with little or no LV hypertropy.36, 37 In a systematic analysis of 1226 relatives of HCM probands, this “restrictive phenotype” of HCM was
Summary
General principles of genetic disease architecture can guide screening and diagnostic approaches for all of the cardiomyopathies and, in fact, for all inherited diseases. At present, the primary benefit of identifying a causal mutation in a proband is to facilitate screening in family members. A preclinical diagnosis achieved through screening programs can allow initiation of further monitoring programs for disease development, avoidance of high-risk behaviors, and potential implementation of
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Cited by (2)
Genomic insights into heart health: Exploring the genetic basis of cardiovascular disease
2024, Current Problems in CardiologyHypertrophic Cardiomyopathy
2013, Nursing Clinics of North AmericaCitation Excerpt :In addition, a decision as to whether or not genetic testing is covered by an insurance plan should be determined prior to genetic testing. The cost of genetic testing for HCM is between $3000 and $5500 for the first person in the family to be tested and $100 and $900 for subsequent family members.41,42 Despite the high cost or the possibility of inconclusive results, genetic testing is cost effective in the management of HCM because should certain family members test negative for the gene mutation there is no need to evaluate or screen their descendants.43