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- HSCR, Hirschsprung disease
- DGGE, denaturing gradient gel electrophoresis
- CIIP, chronic idiopathic intestinal pseudo-obstruction
HSCR is a congenital disorder characterised by an absence of enteric ganglia over various lengths of the bowel and proliferation of nerve fibres in the distal bowel. The absence of enteric ganglia is thought to be caused by a defective migration of neural crest cells. It results in functional obstruction and life threatening bowel distension shortly after birth with an incidence of 1 in 5000 live births. In about 80% of cases, the rectosigmoid colon is the only part affected and in most of the remaining cases the aganglionosis extends to the ileocaecal junction. In a small percentage of cases, the entire small bowel and colon are aganglionic.1
HSCR can be associated with a large number of syndromes, such as Waardenburg syndrome, Smith-Lemli-Opitz syndrome, Goldberg-Shprintzen syndrome, and Ondine's curse. This variety of associated syndromes implies considerable genetic heterogeneity in the aetiology of HSCR, although associations by chance cannot be excluded. Genetic analysis of HSCR has confirmed the heterogeneity. So far, mutations, alone or in combination, have been identified in seven genes, namely RET,2,3GDNF, 4,5NTN,6EDNRB,7EDN3,8,9ECE1,10 and SOX10.11 It is thought that they account for 50-60% of familial cases and 10-30% of sporadic cases.
Besides an association with several syndromes, a difference in sex ratio has also been observed. A male predominance of 3:1 to 5:1 in Hirschsprung disease has been reported.12,13 Badner et al13 performed complex segregation analysis of data on 487 probands and their families. They observed an increased sex ratio, 3.9 males to 1 female, with a decrease when the aganglionosis became more extensive. It is this disturbed sex ratio which made us hypothesise that there might well be a HSCR susceptibility gene on …