The Capital Region's Unit for Inherited Cardiac Diseases, Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
The Capital Region's Unit for Inherited Cardiac Diseases, Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
JACC Heart Fail. 2022 Nov;10(11):792-803. doi: 10.1016/j.jchf.2022.07.009. Epub 2022 Sep 7.
According to patterns of inheritance and incomplete penetrance, fewer than half of relatives to dilated cardiomyopathy probands will develop disease.
The purpose of this study was to investigate the prevalence and incidence, and to identify predictors of developing familial dilated cardiomyopathy (FDC) in relatives participating in family screening.
The study was a retrospective, longitudinal cohort study of families screened and followed from 2006 to 2020 at a regional assembly of clinics for inherited cardiomyopathies.
In total, 211 families (563 relatives, 50% women) were included. At baseline, 124 relatives (22%) were diagnosed with FDC. Genetic sequencing identified the etiology in 37% of screened families and classified 101 (18%) relatives as unaffected carriers (n = 43) or noncarriers (ie, not at risk of FDC [n = 58]). The combined clinical and genetic baseline yield was 30%. During follow-up (2,313 person-years, median 5.0 years), 45 developed FDC (incidence rate of 2.0% per person-year; 95% CI: 1.4%-2.8%), increasing the overall yield to 34%. The incidence rate of FDC was high in relatives with baseline abnormalities on electrocardiogram or echocardiography compared with relatives with normal findings (4.7% vs 0.4% per person-year; HR: 12.9; P < 0.001). In total, baseline screening identified 326 (58%) relatives to be at low risk of FDC.
Family screening identified a genetic predisposition to or overt FDC in 1 of 3 relatives at baseline. Genetic and clinical screening was normal in more than half of relatives, and these relatives had a low risk of developing FDC during follow-up. Thus, baseline screening identified a large proportion, in whom follow-up may safely be reduced, allowing focused follow-up of relatives at risk.
根据遗传模式和不完全外显率，扩张型心肌病先证者亲属中不到一半会发病。
本研究旨在调查家族性扩张型心肌病（FDC）在参加家族筛查的亲属中的患病率和发病率，并确定其预测因素。
本研究是一项回顾性、纵向队列研究，纳入了 2006 年至 2020 年在一个区域性遗传性心肌病诊所联合体进行筛查和随访的家庭。
共纳入 211 个家庭（563 名亲属，50%为女性）。基线时，124 名亲属（22%）被诊断为 FDC。基因测序在 37%的筛查家庭中确定了病因，并将 101 名（18%）亲属归类为无病变携带者（n=43）或非携带者（即无 FDC 风险[n=58]）。临床和基因联合基线检出率为 30%。随访期间（2313 人年，中位随访时间为 5.0 年），45 人发生 FDC（发病率为 2.0%/人年；95%CI：1.4%-2.8%），总检出率增至 34%。与心电图或超声心动图基线正常的亲属相比，基线时心电图或超声心动图异常的亲属 FDC 发病率较高（4.7%比 0.4%/人年；HR：12.9；P<0.001）。基线筛查共确定 326 名（58%）亲属患 FDC 的风险较低。
家族筛查在基线时发现 1/3 的亲属存在 FDC 的遗传易感性或显性疾病。超过一半的亲属基因和临床筛查正常，这些亲属在随访期间发生 FDC 的风险较低。因此，基线筛查确定了很大一部分亲属，他们的随访可以安全减少，从而使风险亲属得到有针对性的随访。
