Digilio M C, Casey B, Toscano A, Calabrò R, Pacileo G, Marasini M, Banaudi E, Giannotti A, Dallapiccola B, Marino B
Departments of Medical Genetics and Pediatric Cardiology, Bambino Gesù Hospital, Rome.
Circulation. 2001 Dec 4;104(23):2809-14. doi: 10.1161/hc4701.099786.
Transposition of the great arteries (TGA) is considered to be associated only rarely with genetic syndromes and to have a low risk of precurrence among relatives of affected patients. Because most family studies have involved a relatively small number of patients and evaluated all types of TGA as a single group, we performed a large, prospective study investigating the precurrence of congenital heart disease in families of children with complete, nonsyndromic TGA.
From January 1997 through December 2000, 370 patients with nonsyndromic, complete TGA were consecutively evaluated and enrolled in the study. The occurrence of cardiac and noncardiac anomalies among relatives of the probands was investigated. Relatives with congenital heart disease were found in 37 of 370 families (10%), including 5 of 37 families (13.5%) with more than one affected relative. TGA itself was the most common precurrent malformation: complete TGA occurred in 6 families and congenitally corrected TGA occurred in 5 families. Precurrence risks for congenital heart disease were calculated at 1.8% (8 of 436) for siblings, 0.5% (4 of 740) for parents, 0.5% (16 of 3261) for first cousins, 0.2% (4 of 2101) for uncles/aunts, and 0.06% (1 of 1480) for grandparents.
The present study shows that TGA is not always sporadic in families. Precurrence of concordant cardiac defects within affected family members supports monogenic or oligogenic inheritance of TGA in certain kindreds. Moreover, the occurrence of complete TGA and congenitally corrected TGA among first-degree relatives in several different families strongly suggests an underlying pathogenetic link between these 2 malformations that has been previously unrecognized.
大动脉转位（TGA）被认为仅很少与遗传综合征相关，且在受影响患者的亲属中复发风险较低。由于大多数家族研究纳入的患者数量相对较少，并且将所有类型的TGA作为一个单一群体进行评估，因此我们进行了一项大型前瞻性研究，调查患有完全性、非综合征性TGA儿童家庭中先天性心脏病的复发情况。
从1997年1月至2000年12月，对370例非综合征性、完全性TGA患者进行连续评估并纳入研究。调查了先证者亲属中心脏和非心脏异常的发生情况。在370个家庭中的37个（10%）发现有先天性心脏病的亲属，其中37个家庭中有5个（13.5%）有不止一名受影响的亲属。TGA本身是最常见的复发畸形：6个家庭发生完全性TGA，5个家庭发生先天性矫正型TGA。计算得出先天性心脏病的复发风险在兄弟姐妹中为1.8%（436例中有8例），父母中为0.5%（740例中有4例），一级表亲中为0.5%（3261例中有16例），叔伯/姑姨中为0.2%（2101例中有4例），祖父母中为0.06%（1480例中有1例）。
本研究表明，TGA在家族中并非总是散发性的。受影响家庭成员中一致性心脏缺陷的复发支持了TGA在某些家族中的单基因或寡基因遗传。此外，在几个不同家庭的一级亲属中出现完全性TGA和先天性矫正型TGA，强烈提示这两种畸形之间存在以前未被认识的潜在致病联系。
