PDF(Pubmed)
Abstract：
Constitutional loss of SMAD4 function results in Juvenile Polyposis-Hereditary Haemorrhagic Telangiectasia Overlap Syndrome (JP-HHT). A retrospective multi-centre case-note review identified 28 patients with a pathogenic SMAD4 variant from 13 families across all Scottish Clinical Genetics Centres. This provided a complete clinical picture of the Scottish JP-HHT cohort. Colonic polyps were identified in 87% (23/28) and gastric polyps in 67% (12/18) of screened patients. Complication rates were high: 43% (10/23) of patients with polyps required a colectomy and 42% (5/12) required a gastrectomy. Colorectal cancer occurred in 25% (7/28) of patients, at a median age of 33 years. Pulmonary arteriovenous malformations were identified in 42% (8/19) of screened patients. 88% (23/26) and 81% (17/21) of patients exhibited JP and HHT features respectively, with 70% (14/20) demonstrating features of both conditions. We have shown that individuals with a pathogenic SMAD4 variant are all at high risk of both gastrointestinal neoplasia and HHT-related vascular complications, requiring a comprehensive screening programme.
摘要：
SMAD4功能的宪法丧失导致青少年息肉病-遗传性出血性毛细血管扩张重叠综合征（JP-HHT）。回顾性多中心病例记录审查从所有苏格兰临床遗传中心的13个家庭中确定了28例具有致病性SMAD4变异的患者。这提供了苏格兰JP-HHT队列的完整临床表现。在87％（23/28）的筛查患者中发现了结肠息肉，在67％（12/18）的患者中发现了胃息肉。并发症发生率很高：43％（10/23）的息肉患者需要结肠切除术，42％（5/12）需要胃切除术。25％（7/28）的患者发生结直肠癌，平均年龄为33岁。在42％（8/19）的筛查患者中发现了肺动静脉畸形。88％（23/26）和81％（17/21）的患者分别表现出JP和HHT特征，70%(14/20)证明了这两种情况的特征。我们已经表明，具有致病性SMAD4变体的个体都处于胃肠道肿瘤和HHT相关血管并发症的高风险中，需要全面的筛查方案。
