Division of Pediatric Cardiology, Department of Pediatrics, Perelman School of Medicine, The Children's Hospital of Philadelphia, The University of Pennsylvania, Philadelphia, Pennsylvania.
Am J Med Genet A. 2014 Jun;164A(6):1490-5. doi: 10.1002/ajmg.a.36500. Epub 2014 Mar 26.
Current recurrence risk counseling for conotruncal cardiac defects (CTD) is based on empiric estimates from multiple studies. We examined the risk of congenital heart disease (CHD) in relatives of probands with CTDs to assist in counseling practices in the current era. One thousand six-twenty probands with CTDs and no reported chromosomal or genetic abnormalities were recruited sequentially. A three-generation pedigree was obtained for each proband by a genetic counselor detailing the presence and type of CHD in each family member. Risks and 95% confidence intervals (CI) were calculated for sub-groups of relatives based on degree of relationship for all probands and by individual lesion of the proband. For pairs of affected relatives, concordance rates were calculated. Severity of CHD in the affected relative was assessed. The risk of CHD was higher in siblings (4.4%, 95% CI 3.4-5.4) than in parents (1.5%, 95% CI 1.1-1.9). Risk varied by the cardiac lesion of the proband with the highest risk in first-degree relatives of probands with tetralogy of Fallot and the lowest in D-transposition of the great arteries. 39% of affected parents and 69% of affected siblings had a concordant lesion (i.e., CTD). Most affected siblings of probands with severe CTDs had complex defects (58%), whereas very few affected parents had complex defects (20%). These data suggest that recurrence risk varies by lesion and relationship, with substantial concordance observed by cardiac lesion and complexity of disease, particularly among siblings. These findings contribute to risk counseling in the current era.
目前，针对圆锥动脉干畸形（CTD）的复发风险咨询主要基于多项研究的经验估计。我们研究了 CTD 先证者亲属的先天性心脏病（CHD）发病风险，以协助当前时代的咨询实践。我们连续招募了 1620 名患有 CTD 且无染色体或遗传异常报告的先证者。每位先证者均由遗传咨询师进行三代家系调查，详细记录每个家庭成员的 CHD 存在情况和类型。根据所有先证者的亲缘关系程度和先证者的个体病变，计算了亲属亚组的风险和 95%置信区间（CI）。对于受影响的亲属对，计算了一致性率。评估了受影响亲属的 CHD 严重程度。与父母（1.5%，95%CI 1.1-1.9）相比，兄弟姐妹的 CHD 发病风险更高（4.4%，95%CI 3.4-5.4）。风险因先证者的心脏病变而异，法洛四联症先证者一级亲属的风险最高，大动脉转位先证者的风险最低。39%的受影响父母和 69%的受影响兄弟姐妹存在一致病变（即 CTD）。大多数患有严重 CTD 的先证者的受影响兄弟姐妹存在复杂缺陷（58%），而受影响父母中很少存在复杂缺陷（20%）。这些数据表明，病变和亲属关系决定了复发风险，通过心脏病变和疾病复杂性观察到显著的一致性，尤其是在兄弟姐妹中。这些发现为当前时代的风险咨询提供了依据。
