Abstract：
Severe gut motility disorders are characterized by the ineffective propulsion of intestinal contents. As a result, the patients develop disabling/distressful symptoms, such as nausea and vomiting along with altered bowel habits up to radiologically demonstrable intestinal sub-obstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility. This syndrome occurs due to changes altering the morpho-functional integrity of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), the interstitial cells of Cajal (ICC) (mesenchymopathy), and smooth muscle cells (myopathy). In the last years, several genes have been identified in different subsets of CIPO patients. The focus of this review is to cover the most recent update on enteric dysmotility related to CIPO, highlighting (a) forms with predominant underlying neuropathy, (b) forms with predominant myopathy, and (c) mitochondrial disorders with a clear gut dysfunction as part of their clinical phenotype. We will provide a thorough description of the genes that have been proven through recent evidence to cause neuro-(ICC)-myopathies leading to abnormal gut contractility patterns in CIPO. The discovery of susceptibility genes for this severe condition may pave the way for developing target therapies for enteric neuro-(ICC)-myopathies underlying CIPO and other forms of gut dysmotility.
摘要：
严重的肠动力障碍的特征在于肠内容物的无效推进。因此,患者出现致残/痛苦的症状，如恶心和呕吐以及排便习惯的改变，直至放射学上可证明的肠道亚阻塞性发作。慢性假性肠梗阻(CIPO)是严重肠动力障碍的典型临床表型。这种综合征是由于改变了内在（肠）神经支配和外在神经供应的形态功能完整性（因此是神经病变）而发生的。Cajal间质细胞（ICC）（间细胞病），和平滑肌细胞（肌病）。在过去的几年里，已在CIPO患者的不同亚群中鉴定出几种基因。本综述的重点是涵盖与CIPO相关的肠动力障碍的最新更新，突出显示（a）具有主要的潜在神经病变的形式，(b)以肌病为主的形式，和（c）线粒体疾病，具有明显的肠道功能障碍作为其临床表型的一部分。我们将对通过最近的证据证明的基因进行彻底的描述，这些基因会导致导致CIPO中异常的肠道收缩模式的神经（ICC）肌病。这种严重疾病的易感基因的发现可能为开发CIPO和其他形式的肠动力障碍的肠神经（ICC）肌病的目标疗法铺平道路。
