Toronto Congenital Cardiac Centre for Adults, University of Toronto, Peter Munk Cardiac Centre, University Health Network/Toronto General Hospital, Ontario, Canada.
Am J Cardiol. 2011 Feb 1;107(3):466-71. doi: 10.1016/j.amjcard.2010.09.045.
The 22.q11.2 deletion syndrome (22q11DS) is a common genetic condition associated with 22q11.2 microdeletions and classically has included congenital heart disease (CHD) as a part of the variable expression. Some evidence has shown that relatives of those with 22q11DS might be at an increased risk of CHD in the absence of 22q11.2 deletions. We obtained a detailed family history of CHD in the first- to third-degree relatives (n = 2,639) of 104 adult probands with 22q11DS. We compared the prevalence of CHD in the relatives without 22q11.2 deletions to the published general population prevalence. We also investigated the effect of CHD in the probands on prevalence of CHD in the relatives. Of the 104 probands with 22q11DS, 14 (13.5%) had 17 relatives (17 of 2,639, 0.6%) with CHD. Of 66 probands with CHD, 15 (0.9%) of their 1,663 relatives had CHD, a significantly greater prevalence than that for the relatives of probands without CHD (0.2%, 2 of 976, p = 0.041, odds ratio 4.43, 95% confidence interval 1.03 to 40.00). In relatives of probands with CHD, the prevalence of those with severe CHD (0.36%) was significantly elevated compared to population expectations (0.061%, p = 0.007, odds ratio 5.88, 95% confidence interval 2.16 to 12.85). In conclusion, these results support a heritable susceptibility to CHD in families of probands with 22q11DS, in addition to that imparted by microdeletion 22q11.2. The occurrence of CHD in relatives might be related to the expression of CHD in the proband with 22q11DS. These findings have potential implications for the genetic counseling of families of those with 22q11DS and support the notion that interacting genetic variants might contribute to the variable expression of 22q11DS.
22q11.2 缺失综合征（22q11DS）是一种常见的遗传疾病，与 22q11.2 微缺失有关，经典的表现形式包括先天性心脏病（CHD）。有证据表明，22q11DS 患者的亲属在没有 22q11.2 缺失的情况下，患 CHD 的风险可能会增加。我们对 104 名 22q11DS 成年患者的一级至三级亲属（n=2639）的 CHD 家族史进行了详细调查。我们将无 22q11.2 缺失的亲属中 CHD 的患病率与一般人群的患病率进行了比较。我们还研究了先证者中 CHD 的存在对亲属中 CHD 患病率的影响。在 104 名 22q11DS 先证者中，有 14 名（13.5%）有 17 名（2639 名中的 17 名，0.6%）亲属患有 CHD。在 66 名患有 CHD 的先证者中，有 15 名（0.9%）的 1663 名亲属患有 CHD，这一患病率明显高于无 CHD 先证者的亲属（0.2%，976 名中的 2 名，p=0.041，优势比 4.43，95%置信区间 1.03 至 40.00）。在患有 CHD 的先证者的亲属中，严重 CHD 的患病率（0.36%）明显高于人群预期（0.061%，p=0.007，优势比 5.88，95%置信区间 2.16 至 12.85）。总之，这些结果支持 22q11DS 先证者的家族存在 CHD 的遗传易感性，除了 22q11.2 微缺失的影响。先证者中 CHD 的发生可能与 22q11DS 先证者中 CHD 的表达有关。这些发现可能对 22q11DS 患者家庭的遗传咨询有影响，并支持相互作用的遗传变异可能导致 22q11DS 表现型可变的观点。
