Associations of anorectal malformations and related syndromes

Abstract

Anorectal malformations (ARMs) represent a complex group of congenital anomalies resulting from abnormal development of the hindgut, allantois and Mullerian duct resulting in complete or partial urorectal septal malformations. There is a wide variety of phenotypic expression, ranging from mild anorectal to very complex severe ARM with >75 % having other associated malformations. 50 % of cases are syndromic although many may have other associated anomalies. This suggests a genetic link but the genetics of ARM are highly complex with a number of candidate genes being identified. Many can be classified as "field defects" as a result of a complex set of genetic interactions. Patients with associated malformations can be classified into those with multiple congenital anomalies (non-syndromic), those with chromosomal abnormalities and those with non-chromosomal syndromic associations, also, those with non-chromosomal syndromes and the influence of environmental factors (e.g. drugs in pregnancy). Although much is not known about the aetiology of ARM, the weight of evidence points to genetic factors as major causes for the condition. In this review, we look at the chromosomal and genetic associations and their underlying signalling pathways, to obtain a better understanding of the pathogenetic mechanisms involved in developing ARM. The spectrum of ARM phenotypic expression probably results from involvement and crosstalk between a number of critical signalling systems involved in development of this region. As a result, it may be expressed as a "field developmental defect" with many associated abnormalities. The role of environmental factors in the development of ARM is probably less.

STAR syndrome is part of the differential diagnosis of females with anorectal malformations

“…The incidence of associated anomalies varies between 40% and 70% [Wijers et al, ]. While the etiology of ARM is not completely known yet, it appears to be multifactorial with both genetic and environmental factors [Moore, ]. STAR syndrome (OMIM 300707) is an X‐linked dominant developmental disorder whose features include toe syndactyly, telecanthus, and anogenital/renal malformations [Unger et al, ].…”

Birth outcomes of patients with isolated anorectal malformations: A population‐based case‐control study

“…The etiology of ARM is less known, the weight of evidence points to genetic factors as major causes of ARMs (Moore 2013). Many candidate genes have been identified (Guo et al 2014;Miyagawa et al 2014;Ng et al 2014).…”

Genome‐wide mapping of copy number variations in patients with both anorectal malformations and central nervous system abnormalities

“…The observation of the occurrence of ARM in two independent events in our cohort and the previously reported association between 22q11.2 deletions and ARM suggests this region to be undoubtedly involved in the expression of anorectal development. However, as outlined by Moore (), ARM are highly heterogenous and may be expressed as a “developmental field defect,” with many associated abnormalities. The author suggested, that the spectrum of ARM phenotypic expression probably results from involvement and crosstalk between several critical signaling systems.…”