Advances in understanding functional variations in the Hirschsprung disease spectrum (variant Hirschsprung disease)

Pediatr Surg Int. 2017 Mar;33(3):285-298. doi: 10.1007/s00383-016-4038-3. Epub 2016 Dec 17.


Hirschsprung disease (HSCR) is a fairly well understood congenital, genetically based functional obstruction due to the congenital absence of ganglion cells in the distal bowel. However, although over 90% of Hirschsprung cases conform to the normally accepted histological diagnostic criteria, it has become increasingly clear that in addition to HSCR, there is a group of functional disturbances relating to a number of other congenital neurodysplastic conditions causing some degree of gastrointestinal tract malfunction. Although these represent a variety of possibly separate conditions of the enteric nervous system, this spectrum it would appear to be also influenced by similar developmental processes. The term "variant Hirschsprung" is commonly used to describe these conditions, but ganglion cells are mostly present if abnormal in number and distribution. These conditions are a problem group being amongst the most difficult to diagnose and treat with possible practical and legal consequences. The problem appears to be possibly one of definition which has proven difficult in the relative paucity of normal values, especially when correlated to age and gestation. It is the purpose of this paper to review the current position on these conditions and to explore possible shared common pathogenetic and genetic mechanisms. This article explores those conditions where a similar pathogenetic mechanisms to HSCR can be demonstrated (e.g. hypoganglionosis) as well as other neural features, which appear to represent separate conditions possibly linked to certain syndromes.

Keywords: Endothelin B receptor gene; Enteric nervous system; Functional gastrointestinal obstruction; Genetics; Hyperganglionosis; Hypoganglionosis; RET protooncogene; Variant Hirschsprung disease.

Publication types

  • Review

MeSH terms

  • Child
  • Enteric Nervous System / physiopathology*
  • Female
  • Hirschsprung Disease / diagnosis*
  • Hirschsprung Disease / physiopathology*
  • Humans