Sudden cardiac death in familial hypertrophic cardiomyopathy: are “benign” mutations really benign?

Semsarian, C.; Yu, Bing; Ryce, C.; Lawrence, C. J.; Washington, H.; Trent, Ronald J.

doi:10.1080/00313029700169155

Cited by 31 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although initial studies supported the notion of mutation-specific clinical outcomes, 25 subsequent studies 26 and the identification of the vast clinical and genetic heterogeneity in HCM have limited the clinical utility of genotype in guiding management. 1,27 In the current study, MYH7 mutation carriers were found to be significantly younger, and they presented at a younger age, as compared with MYBPC3 mutation carriers.…”

Section: Discussionmentioning

confidence: 99%

Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy

Ingles

Sarina

Yeates

et al. 2013

Genetics in Medicine

123

View full text Add to dashboard Cite

Purpose: Genetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified. Methods:Probands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected.Results: A total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012). Conclusion:Family history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy

Ingles

Sarina

Yeates

et al. 2013

Genetics in Medicine

123

View full text Add to dashboard Cite

show abstract

“…Indeed, several early studies of HCM pedigrees implicated certain mutations as "malignant" (20,227,345,346). However, subsequent studies of less selected consecutive patients with HCM found that it was problematic to infer likelihood of SCD events on the basis of the proposed mutations, because in some instances the rate of adverse events (and prevalence of associated SCD risk markers) was lower in patients with "malignant" mutations than it was in those with mutations believed to be "benign" (8,(347)(348)(349). The data from unselected consecutive outpatients suggest that most mutations are "novel" and limited to particular families ("private" mutations).…”

Section: Genetic Mutationsmentioning

confidence: 96%

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary

Gersh¹,

Maron²,

Bonow³

et al. 2011

Journal of the American College of Cardiology

257

View full text Add to dashboard Cite

“…Although defects in some genes have been associated with different degrees of disease penetrance, for example, mutations in the h-myosin heavy chain gene show 90% disease penetrance by age 20 years compared to 30% penetrance at the same age with myosin-binding protein-C mutations [7,8], many families have been described in which affected individuals within the same family (and therefore carrying the same gene defect) have vastly different clinical outcomes [9]. Furthermore, specific mutations previously described as bbenignQ or bmalignantQ have been shown to cause a diverse range of severity of disease [10]. Collectively, these data strongly suggest that modifying factors, both genetic and/or environmental, play an important role in explaining the phenotypic diversity seen in hypertrophic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 96%