Bianco Francesca, Bonora Elena, Lattanzio Giulia, Clavenzani Paolo, Guarino Matteo, Mazzoni Maurizio, Baldassarro Vito Antonio, Lorenzini Luca, Caio Giacomo, Stanghellini Vincenzo, Sternini Catia, Farrugia Gianrico, Giardino Luciana, Calzà Laura, De Giorgio Roberto
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Department of Veterinary Sciences University of Bologna, Bologna, Italy.
Adv Exp Med Biol. 2022;1383:9-17. doi: 10.1007/978-3-031-05843-1_2.
Severe gut motility disorders are characterized by ineffective propulsion of intestinal contents. As a result, patients often develop extremely uncomfortable symptoms, ranging from nausea and vomiting along with alterations of bowel habits, up to radiologically confirmed subobstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility due to morphological and functional alterations of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), interstitial cells of Cajal (ICCs) (mesenchymopathy), and smooth muscle cells (myopathy). In this chapter, we highlight some molecular mechanisms of CIPO and review the clinical phenotypes and the genetics of the different types of CIPO. Specifically, we will detail the role of some of the most representative genetic mutations involving RAD21, LIG3, and ACTG2 to provide a better understanding of CIPO and related underlying neuropathic or myopathic histopathological abnormalities. This knowledge may unveil targeted strategies to better manage patients with such severe disease.
严重的肠道动力障碍的特征是肠内容物推进无效。因此，患者常常出现极其不适的症状，从恶心、呕吐以及排便习惯改变，到经放射学证实的亚梗阻发作。慢性肠假性梗阻（CIPO）是严重肠道动力障碍的典型临床表型，其病因是内在（肠）神经支配和外在神经供应（即神经病变）、Cajal间质细胞（ICC）（间充质病变）和平滑肌细胞（肌病）的形态和功能改变。在本章中，我们重点介绍CIPO的一些分子机制，并回顾不同类型CIPO的临床表型和遗传学。具体而言，我们将详细阐述涉及RAD21、LIG3和ACTG2的一些最具代表性的基因突变的作用，以便更好地理解CIPO以及相关的潜在神经病变或肌病组织病理学异常。这些知识可能揭示出更有效的针对性策略，用于更好地管理患有这种严重疾病的患者。
