Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, France (M.T., L.L.G., C.D., R.R., J.-J.S., A.-E.B.).
Nantes Université, CHU Nantes, Department of Pediatric Cardiology and Pediatric Cardiac Surgery, France (M.T., S.P., C.G.G., B.R., N.B., Q.H., A.-E.B.).
Circ Genom Precis Med. 2022 Jun;15(3):e003464. doi: 10.1161/CIRCGEN.121.003464. Epub 2022 May 12.
Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns.
An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands.
Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia.
ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.
先天性矫正型大动脉转位（ccTGA）是一种病因不明的罕见疾病。我们旨在更好地了解家族内的复发模式。
在 1990 年至 2018 年间，我们在 6 个国家的 29 家三级医院进行了一项国际性、多中心、回顾性队列研究，共纳入了 1043 名无关的 ccTGA 先证者。
分别有 29.9%和 9.3%的患者存在侧位缺陷和房室传导阻滞。11 例患者存在原发性纤毛运动障碍。3.4%的病例存在父母近亲婚配。在 69 个家庭的 81 名亲属中诊断出先天性心脏病，其中 58%为一级亲属，包括 28 名兄弟姐妹。亲属中最常见的缺陷是大动脉右旋转位（28.4%）、侧位缺陷（13.6%）和 ccTGA（11.1%）；共描述了 36 个新的家族聚集，包括 8 个具有 ccTGA 家族聚集的家系、19 个具有 ccTGA 和大动脉右旋转位家族共分离的家系、以及 9 个具有 ccTGA 和侧位缺陷家族共分离的家系。在一个家族中，ccTGA、大动脉右旋转位和异构综合征在 3 个不同的亲属中共同分离。在另一个家族中，双胞胎均表现出 ccTGA 和原发性纤毛运动障碍。
ccTGA 并非总是散发性先天性心脏病。家族聚集以及 ccTGA 与大动脉右旋转位、侧位缺陷的关联证据，在某些情况下还与原发性纤毛运动障碍的关联证据强烈提示，在 ccTGA 的病理生理学中，存在涉及侧位基因的共同致病途径。
