背景:MYH7变异导致肥厚型心肌病(HCM),心肌致密化不全(NCCM),和扩张型心肌病(DCM)。建议从10至12岁开始筛查遗传性心肌病患者的亲属,不管受影响的基因。
目的:本研究旨在研究MYH7变异型相关心肌病的外显率和预后。
方法:在这项多中心队列研究中,通过Kaplan-Meier曲线和对数秩检验,对(可能)致病性MYH7变异体携带者的外显率和主要心肌病相关事件(MCE)进行了评估.使用具有时间依赖性系数的Cox回归评估预后因素。
结果:总计,581名受试者(30.1%指数患者,48.4%男性,包括中位年龄37.0岁[IQR:19.5-50.2岁])。226名受试者被诊断出HCM,NCCM在70,DCM在55。早期外显率和MCE(年龄<12岁)在NCCM相关变异携带者中很常见(21.2%和12.0%,分别)和DCM相关变异携带者(15.3%和10.0%,分别),与HCM相关变异携带者(2.9%和2.1%,分别)。NCCM相关或DCM相关变异型携带者(调整后HR:1.87;95%CI:1.15-3.04;P=0.012)和年龄≤1岁时,在NCCM相关或DCM相关变异型携带者(调整后HR:21.17;95%CI:4.81-93.20;P<0.001)和有早期MCEs家族史的受试者(调整后HR:2.45;95%CI:1.有早期MCE家族史的受试者(调整后的HR:1.82;95%CI:1.15-2.87;P=0.010),NCCM相关或DCM相关变异携带者年龄≤5岁时MCE的风险增加(调整后的HR:38.82;95%CI:5.16-291.88;P<0.001)。
结论:MYH7变异体可在年轻时引起心肌病和MCE。可能需要在较年轻的年龄进行筛查,特别是在NCCM或DCM相关变体的携带者和/或在<12岁时有MCEs家族史。
BACKGROUND: MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.
OBJECTIVE: This
study sought to
study the penetrance and prognosis of
MYH7 variant-associated cardiomyopathies.
METHODS: In this multicenter cohort
study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic
MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.
RESULTS: In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).
CONCLUSIONS: MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.