Mowat-Wilson 综合征与先天性巨结肠病：一项关于功能预后的回顾性研究。

Mowat Wilson syndrome and Hirschsprung disease: a retrospective study on functional outcomes.

机构信息

Department of Pediatric Surgery and Urology, Robert Debré Children University Hospital, APHP, 48 boulevard Sérurier, 75019, Paris, France.

Paris University, Paris, France.

出版信息

Pediatr Surg Int. 2020 Nov;36(11):1309-1315. doi: 10.1007/s00383-020-04751-8. Epub 2020 Sep 27.

DOI:10.1007/s00383-020-04751-8

PMID:32980962

Abstract

AIM OF THE STUDY

Mowat Wilson syndrome (MWS) is a complex genetic disorder due to mutation or deletion of the ZEB2 gene (ZFHX1B), including multiple clinical features. Hirschsprung disease is associated with this syndrome with a prevalence between 43 and 57%. The aim of this study was to demonstrate the severe outcomes and the high complication rates in children with MWS, focusing on their complicated follow-up.

METHODS

A retrospective comparative study was conducted on patients referred to Robert-Debré Children's Hospital for MWS from 2003 to 2018. Multidisciplinary follow-up was carried out by surgeons, geneticists, gastroenterologists, and neurologists. Data regarding patient characteristics, surgical management, postoperative complications, and functional outcomes were collected.

RESULTS

Over this period of 15 years, 23 patients were diagnosed with MWS. Hirschsprung disease was associated with 10 of them (43%). Of these cases, two patients had recto-sigmoïd aganglionosis (20%), three had aganglionic segment extension to the left colic angle (30%), two to the right colic angle (20%), and three to the whole colon (30%). The median follow-up was 8.5 years (2 months-15 years). All patients had seizures and intellectual disability. Six children (60%) presented with cardiac defects. At the last follow-up, three patients still had a stoma diversion and 7 (70%) were fed orally. One patient died during the first months. Eight (80%) of these children required a second surgery due to complications. At the last follow-up, three patients reported episodes of abdominal bloating (42%), one recurrent treated constipation (14.3%), and one soiling (14.3%). Genetic analysis identified three patients with heterozygous deletions, three with codon mutations, and three with frameshift mutations.

CONCLUSIONS

MWS associated with Hirschsprung disease has a high rate of immediate surgical complications but some patients may achieve bowel function comparable with non-syndromic HD patients. A multidisciplinary follow-up is required for these patients.

LEVEL OF EVIDENCE

Retrospective observational single cohort study, Level 3.

摘要

研究目的

Mowat-Wilson 综合征（MWS）是一种由于 ZEB2 基因（ZFHX1B）突变或缺失引起的复杂遗传疾病，包括多种临床特征。先天性巨结肠症与该综合征相关，患病率在 43%至 57%之间。本研究旨在展示 MWS 患儿的严重后果和高并发症发生率，重点关注其复杂的随访情况。

方法

对 2003 年至 2018 年期间因 MWS 就诊于罗伯特-德布雷儿童医院的患者进行回顾性对比研究。外科医生、遗传学家、胃肠病学家和神经学家进行了多学科随访。收集了患者特征、手术管理、术后并发症和功能结局的数据。

结果

在这 15 年期间，诊断出 23 例 MWS 患者。其中 10 例（43%）合并先天性巨结肠症。这些病例中，2 例为直肠-乙状结肠无神经节细胞症（20%），3 例无神经节细胞肠段延伸至左结肠角（30%），2 例延伸至右结肠角（20%），3 例延伸至整个结肠（30%）。中位随访时间为 8.5 年（2 个月至 15 年）。所有患者均有癫痫发作和智力障碍。6 例患儿（60%）存在心脏缺陷。末次随访时，3 例仍有肠造口术，7 例（70%）经口进食。1 例患儿在最初几个月死亡。其中 8 例（80%）因并发症需要再次手术。末次随访时，3 例患儿诉腹胀（42%），1 例复发性便秘（14.3%），1 例大便失禁（14.3%）。基因分析发现 3 例患者存在杂合性缺失，3 例存在密码子突变，3 例存在移码突变。