Hydrocephalus with Hirschsprung disease: Severe end of X-linked hydrocephalus spectrum

Toshiki Takenouchi, Mie Nakazawa, Yonehiro Kanemura, Sachiko Shimozato, Mami Yamasaki, Takao Takahashi, Kenjiro Kosaki

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


L1CAM molecule is a cell adhesion molecule in nervous and enteric systems and is responsible for X-linked hydrocephalus (XLH) spectrum, which is a rare condition with severe congenital hydrocephalus, dysgenesis of the corpus callosum, intellectual disability, spasticity, and adducted thumbs. Several cases of XLH accompanied by Hirschsprung disease (HSCR) have been reported in the literature, but whether HSCR results from a gain-of-function mutation in cases with XLH, i.e., a neomorphic mutation, or the severe end of the L1CAM mutation spectrum remains unclear. The present patient was a Japanese boy with severe congenital hydrocephalus with aqueductal stenosis as well as hypoplasia of the corpus callosum. HSCR had been confirmed by a biopsy. A mutation analysis of the L1CAM gene showed a C61T mutation in exon 1, resulting in a truncating nonsense mutation at amino acid position 21 and producing an extremely short protein that was unlikely to interact with other proteins. These findings suggest that XLH-HSCR represents the severe end of the XLH spectrum, rather than a neomorphic mutation. A thorough abdominal investigation to rule out HSCR should be considered in patients with XLH accompanied by severe constipation.

Original languageEnglish
Pages (from-to)812-815
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number4
Publication statusPublished - 2012 Apr


  • Hirschsprung disease
  • Hydrocephalus
  • Neural cell adhesion molecule L1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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