You are here

Article Text

Article menu
Download PDFPDF
Electronic letters
Hirschsprung disease and L1CAM: is the disturbed sex ratio caused by L1CAM mutations?
  1. R M W Hofstra1,
  2. P Elfferich1,
  3. J Osinga1,
  4. E Verlind1,
  5. E Fransen2,
  6. J López Pisón3,
  7. C E M de Die-Smulders4,
  8. I Stolte-Dijkstra1,
  9. C H C M Buys1
  1. 1Department of Medical Genetics, University of Groningen, The Netherlands
  2. 2Department of Biochemistry, University of Antwerp, Belgium
  3. 3Sección Neuropediatría, Hospital Infantil Miguel Servet, Zaragoza, Spain
  4. 4Department of Clinical Genetics, Academic Hospital, Maastricht, The Netherlands
  1. Correspondence to:
 Dr R M W Hofstra, Department of Medical Genetics, Ant Deusinglaan 4, 9713 AW Groningen, The Netherlands;
 R.M.W.Hofstra{at}medgen.azg.nl

https://doi.org/10.1136/jmg.39.3.e11

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    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 …

    View Full Text