Hydrocephalus and intestinal aganglionosis: Is L1CAM a modifier gene in Hirschsprung disease?
Article first published online: 16 JAN 2002
Copyright © 2002 Wiley-Liss, Inc.
American Journal of Medical Genetics
Volume 108, Issue 1, pages 51–56, 15 February 2002
How to Cite
Parisi, M. A., Kapur, R. P., Neilson, I., Hofstra, R. M.W., Holloway, L. W., Michaelis, R. C. and Leppig, K. A. (2002), Hydrocephalus and intestinal aganglionosis: Is L1CAM a modifier gene in Hirschsprung disease?. Am. J. Med. Genet., 108: 51–56. doi: 10.1002/ajmg.10185
- Issue published online: 16 JAN 2002
- Article first published online: 16 JAN 2002
- Manuscript Accepted: 11 OCT 2001
- Manuscript Received: 8 MAR 2001
- X-linked hydrocephalus;
- adducted thumbs;
- aqueductal stenosis;
- Hirschsprung disease;
Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM-mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease–associated gene to cause intestinal aganglionosis. © 2002 Wiley-Liss, Inc.