Molecular Genetics of Development Laboratory, Department of Biological Sciences, University of Quebec at Montreal, Canada.
Clin Genet. 2013 Jan;83(1):15-22. doi: 10.1111/cge.12032. Epub 2012 Nov 7.
Hirschsprung's disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). It displays an incidence of 1 in 5000 live births with a 4:1 male to female sex ratio. Clinical signs include severe constipation and distended bowel due to a non-motile colon. If left untreated, aganglionic megacolon is lethal. This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells. These progenitor cells are derived from a transient stem cell population called neural crest cells (NCC). The genetics of HSCR is complex and can involve mutations in multiple genes. However, it is estimated that mutations in known genes account for less than half of the cases of HSCR observed clinically. The male sex bias is currently unexplained. The objective of this review is to provide an overview of the pathophysiology and genetics of HSCR, within the context of our current knowledge of NCC development, sex chromosome genetics and laboratory models.
先天性巨结肠（HSCR），又称无神经节细胞巨结肠，源于肠神经系统（ENS）的先天性畸形。其发病率为每 5000 例活产儿中出现 1 例，男女比例为 4:1。临床症状包括严重的便秘和结肠扩张，由于结肠无蠕动。如果不治疗，无神经节细胞性巨结肠是致命的。这种严重的先天性疾病是由于结肠神经节缺失，以及由此导致的结肠内在神经支配缺乏，这是由于 ENS 祖细胞在发育肠道中的定植不当所致。这些祖细胞来源于一种称为神经嵴细胞（NCC）的短暂干细胞群体。HSCR 的遗传学很复杂，可能涉及多个基因的突变。然而，据估计，临床上观察到的 HSCR 病例中，已知基因突变不到一半。男性的性别偏好目前还无法解释。本综述的目的是在我们目前对 NCC 发育、性染色体遗传学和实验室模型的认识背景下，概述 HSCR 的病理生理学和遗传学。
