Oesophageal atresia, tracheo-oesophageal fistula and the VACTERL association: review of genetics and epidemiology. Charles Shaw-Smith Department of Medical Genetics, Addenbrooke’s Hospital, Cambridge CB2 2QQ, Address for correspondence:

Oesophageal atresia and/or tracheo-oesophageal fistula are common malformations occurring in approximately 1 in 3500 births. In around half of cases (syndromic oesophageal atresia), there are other associated anomalies, with cardiac malformations being the most common. These may occur as part of the VACTERL association (OMIM 192350). In the remainder of cases, oesophageal atresia/tracheo-oesophageal fistula occur in isolation (non-syndromic oesophageal atresia). Data from twin and family studies suggest that, in the majority of cases, genetic factors do not play a major role, and yet there are well-defined instances of this malformation where genetic factors clearly are important. This is highlighted by the recent identification of no fewer than three separate genes with a role in the aetiology of oesophageal atresia. These are the genes for Feingold syndrome (N-MYC, OMIM 164280), anophthalmia-oesophageal-genital (AEG) syndrome (SOX2, OMIM 600992) and CHARGE syndrome (CHD7, OMIM 214800). Additional support for genetic factors in this malformation comes from chromosomal studies and mouse models. This paper reviews current knowledge of the genetics and epidemiology of the different oesophageal atresia/tracheo-oesophageal fistula syndromes and associations. group.bmj.com on October 14, 2017 Published by http://jmg.bmj.com/ Downloaded from