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

Raquel M Fernández,Antonio González-Meneses,Salud Borrego,Rocío Núñez-Torres,Guillermo Antiñolo

doi:10.1186/1471-2350-11-137

Abstract

BackgroundHirschsprung 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.MethodsA combination of MLPA and microarray data analysis have been undertaken to refine a duplication at the Xq28 region.ResultsIn 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.ConclusionsWhile 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.

Highlights

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
The question of L1CAM being a modifier gene in HSCR has been raised with no definitive answer given far [7,8], the whole data suggest that mutations in L1CAM may be involved in HSCR development in association with a predisposing background [9]
In this report we present a clinical case of neonatal severe encephalopathy (OMIM 300673) associated with HSCR, presenting with a duplication in the X chromosome encompassing the MECP2 (OMIM 300005) and L1CAM genes among others

Summary

Introduction

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. Hirschsprung disease (HSCR, OMIM 142623) is a congenital malformation of the hindgut characterised by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses. It is regarded as the consequence of the premature arrest of the craniocaudal migration of vagal neural crest cells in the hindgut between the fifth and 12th week of gestation to form the enteric nervous system (ENS) and is regarded as a neurocristopathy [1]. Associated congenital anomalies are found in 18% of the HSCR patients Among those HSCR-associated syndromes, there exist some clinical presentations with central nervous system anomalies, including the HSAS/MASA spectrum (OMIM 307000 and 303350) ascribed to mutations in the X-linked L1CAM gene [1,4]. The question of L1CAM being a modifier gene in HSCR has been raised with no definitive answer given far [7,8], the whole data suggest that mutations in L1CAM may be involved in HSCR development in association with a predisposing background [9]

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Results

Discussion

Conclusion