Pediatric Surgery International

, Volume 34, Issue 1, pp 9–20 | Cite as

A review of genetic factors contributing to the etiopathogenesis of anorectal malformations

  • Kashish Khanna
  • Shilpa Sharma
  • Noel Pabalan
  • Neetu Singh
  • D. K. Gupta
Review Article



Anorectal malformation (ARM) is a common congenital anomaly with a wide clinical spectrum. Recently, many genetic and molecular studies have been conducted worldwide highlighting the contribution of genetic factors in its etiology. We summarize the current literature on such genetic factors.

Materials and methods

Literature search was done using different combinations of terms related to genetics in anorectal malformations. From 2012 to June 2017, articles published in the English literature and studies conducted on human population were included.

Observations and results

A paradigm shift was observed from the earlier studies concentrating on genetic aberrations in specific pathways to genome wide arrays exploring single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in ARM patients. Rare CNVs (including 79 genes) and SNPs have been found to genetically contribute to ARM. Out of disrupted 79 genes one such putative gene is DKK4. Down regulation of CDX-1 gene has also been implicated in isolated ARM patients. In syndromic ARM de novo microdeletion at 17q12 and a few others have been identified.


Major genetic aberrations proposed in the pathogenesis of ARM affect members of the Wnt, Hox (homebox) genes, Sonic hedgehog (Shh) and Gli2, Bmp4, Fgf and CDX1 signalling pathways; probable targets of future molecular gene therapy.


Anorectal malformations Genetic factors Etiology Copy number variations Chromosomal aberrations Single nucleotide polymorphisms 



Anorectal malformation


Anterior Intestinal portal


Caudal Intestinal portal


Copy number variation


Single nucleotide polymorphism


Sonic hedgehog




Autosomal dominant


Autosomal recessive


Currarino syndrome


Compliance with ethical standards

Conflict of interest

No conflict of interest exists.


There is no financial support or funding to declare.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Pediatric SurgeryAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Center for Research and DevelopmentAngeles University FoundationAngelesPhilippines
  3. 3.Molecular Biology Unit, Center for Advance ResearchKing George’s Medical UniversityLucknowIndia

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