Cornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. We retrospectively collected data from 23 CdLSp patients, 13 females and 10 males. Mean age of the patients undergoing surgical treatment was of 4 years. 21/23 (91%) had a molecular characterization, of which 21/21 (100%) had a NIPBL gene mutation, while 2/23 (9%) did not have a genetical characterization, only a clinical diagnosis. Most of our patients presented a moderate–severe severity score (21/23, 91%) with limb malformations evidenced in 10/23 (44%) of our patients and a moderate–severe intellectual disability in 20/23 (87%). Therefore, CdLSp patients harboring NIPBL variants, upper limb malformations and severe psychomotor delay are more likely to suffer from severe GERD, not responsive to proton pump inhibitors treatment. These features should be considered as clinical markers for potentially severe GERD that might require surgical treatment.

中文翻译：

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Cornelia de Lange综合征谱中的Nissen胃底折叠术：谁是潜在的候选人？

Cornelia de Lange谱（CdLSp）是一种罕见的遗传疾病，其特征是智力残疾，面部畸形，严重畸形，生长障碍和发育延迟。大约80％的CdLSp患者患有胃食管反流病（GERD），临床表现各异。这项研究的目的是根据接受外科手术治疗的患有严重GERD的CdLSp患者的临床表型描述，确定潜在的临床/遗传危险因素。我们回顾性收集了23例CdLSp患者，13例女性和10例男性的数据。接受手术治疗的患者的平均年龄为4岁。21/23（91％）具有分子特征，其中21/21（100％）具有NIPBL基因突变，而2/23（9％）没有遗传特征，仅具有临床诊断。我们的大多数患者表现出中度至重度评分（21/23，91％），其中肢体畸形在我们的患者中占10/23（44％），在中度至重度智力残疾中在20/23（87％）中。因此，具有NIPBL变异，上肢畸形和严重的精神运动延迟的CdLSp患者更有可能患有严重的GERD，对质子泵抑制剂治疗无反应。这些特征应被视为可能需要手术治疗的潜在严重GERD的临床标志。对质子泵抑制剂治疗无反应。这些特征应被视为可能需要手术治疗的潜在严重GERD的临床标志。对质子泵抑制剂治疗无反应。这些特征应被视为可能需要手术治疗的潜在严重GERD的临床标志。