Genetics of atrioventricular canal defects

Pugnaloni F, Digilio MC, Putotto C, De Luca E, Marino B, Versacci P.Ital J Pediatr. 2020 May 13;46(1):61. doi: 10.1186/s13052-020-00825-4.PMID: 32404184 Free PMC article. Review.



Atrioventricular canal defect (AVCD) represents a quite common congenital heart defect (CHD) accounting for 7.4% of all cardiac malformations. AVCD is a very heterogeneous malformation that can occur as a phenotypical cardiac aspect in the context of different genetic syndromes but also as an isolated, non-syndromic cardiac defect. AVCD has also been described in several pedigrees suggesting a pattern of familiar recurrence. Targeted Next Generation Sequencing (NGS) techniques are proved to be a powerful tool to establish the molecular heterogeneity of AVCD.Given the complexity of cardiac embryology, it is not surprising that multiple genes deeply implicated in cardiogenesis have been described mutated in patients with AVCD. This review attempts to examine the recent advances in understanding the molecular basis of this complex CHD in the setting of genetic syndromes or in non-syndromic patients.



Fig. 1 Distribution of AVCD with and without Down syndome modified by Digilio, M.C.; Marino, B.;Toscano, A.; Giannotti, A.; Dallapiccola, B. Atrioventricular canal defect without Down syndrome: a heterogeneous malformation. Am J Med Genet. 1999 Jul 16;85(2):140–6. (a) Mendelian Disorders: Noonan, Ellis-van Crevels, VACTERL, Oro-facio-digital II, Smith-Lemli-Opitz, DiGeorge,Bardet-Biedl, CHARGE. (b) Extracardiac malformations: Facial anomalies,dental anomalies, skeletal anomalies,gastrointestinal anomalies, glaucoma, mental retardation, (c) Chromosome imbalance: del 8 p21-pter; del 8 p23-pter; del 8 p21-p23;del4 q31-q32; 47, XX, + 18; 47, XY,+ 9;45,X


Fig. 2 a Coronal sonogram of fetal head with alobar holoprosencephaly. b Echocardiographic subcostal view of common atrioventricular valve in the context of complete AVCD. CV: common valve


Fig. 3 Genes involved in different forms of atrioventricular canal defects