VATER/VACTERL association

Abstract

The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. The identification of 14 twin pairs with an initial diagnosis of VATER/VACTERL association at our clinical centers led to the performance of a classical twin study. This involved a thorough evaluation of these 14 twin pairs and a further 55 twin pairs identified from a systematic review of the literature. The zygosity, concordance, and malformation status of all 69 twin pairs were evaluated. Twenty-four twin pairs fulfilled the criteria for inclusion in a comparison of the concordance rates between monozygous (MZ) and dizygous (DZ) twin pairs. The pairwise concordance rates were 15% [95% confidence interval (CI) 4–42%] for MZ and 18% (95% CI 5–48%) for DZ twin pairs (P = 0.53). The probandwise concordance rates were 27% (95% CI 11–52%) for MZ and 31% (95% CI 13–58%) for DZ twin pairs (P= 0.40). Although based on a limited number of twin pairs, the findings of the present study are consistent with the low number of familial cases reported to date, and suggest that the role of inherited genetic factors in the majority of VATER/VACTERL cases is limited.

Mutation Screening and Array Comparative Genomic Hybridization Using a 180K Oligonucleotide Array in VACTERL Association

“…Recent twin studies support a low proportion of genetic abnormalities found in VACTERL patients [33], [34].…”

Recurrent constellations of embryonic malformations re‐conceptualized as an overlapping group of disorders with shared pathogenesis

“…Reports where zygosity was not reported (for example, the author did not comment on whether the twins were thought to be monozygotic or dizygotic) were excluded. Because twin studies on OAVS and VACTERL that relied on exhaustive literature searches had been previously published (Bartels et al, 2012;Wieczorek et al, 2007), we relied on references from these studies in addition to performing PubMed searches using the search terms in Table 3 to capture relevant literature that had been published after 2007 and 2012, respectively, for these two conditions. Our literature search terms are summarized in Table 3.…”

“…but this has only been tested statistically for VACTERL (Bartels et al, 2012) and OAVS (Wieczorek et al, 2007). Given the retrospective nature of the reports included in our analysis, many providing only partial data on zygosity, we chose to analyze zygosity directly from data provided in the reports and indirectly using Weinberg's differential rule (Fellman & Eriksson, 2006), expecting the latter to be more accurate as it is free of reporting bias.…”

“…Each of these associations or syndromes share an early embryonic origin, no (or extremely rare) reports of familial recurrence (Backhouse et al, 2019;Chen et al, 2018;Solomon, 2018), and an excess of reported discordant twins and other multiple births (Bartels et al, 2012;Wieczorek et al, 2007). They share other common features as well.…”

“…The mutual association between RCEM disorders and twins, especially discordant MZ twins (Arteaga-Vázquez et al, 2019;Bartels et al, 2012;Dawson et al, 2016;Keppler-Noreuil et al, 2007;Kunapinun & Treetipsatit, 2017;Solomon et al, 2013;Werler et al, 2004;Wieczorek et al, 2007), separates them from other molecularly unsolved disorders such as Aicardi and Hallermann-Streiff syndromes (Boycott et al, 2018). Further, the few reports of genetic abnormalities have involved singletons and not twins.…”