Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region

BMC Med Genet. 2010 Sep 22:11:137. doi: 10.1186/1471-2350-11-137.

Abstract

Background: Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes.

Methods: A combination of MLPA and microarray data analysis have been undertaken to refine a duplication at the Xq28 region.

Results: In this study we present a new clinical association of severe neonatal encephalopathy (Lubs syndrome) and HSCR, in a male patient carrying a duplication at the Xq28 region which encompasses the MECP2 and L1CAM genes.

Conclusions: While the encephalopathy has been traditionally attributed to the MECP2 gene duplication in patients with Lubs syndrome, here we propose that the enteric phenotype in our patient might be due to the dosage variation of the L1CAM protein, together with additional molecular events not identified yet. This would be in agreement with the hypothesis previously forwarded that mutations in L1CAM may be involved in HSCR development in association with a predisposing genetic background.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases / complications
  • Brain Diseases / congenital
  • Brain Diseases / genetics*
  • Chromosomes, Human, X*
  • DNA Mutational Analysis
  • Gene Duplication*
  • Genome-Wide Association Study
  • Hirschsprung Disease / complications
  • Hirschsprung Disease / genetics*
  • Humans
  • Infant, Newborn
  • Male
  • Pedigree
  • Severity of Illness Index
  • Syndrome