Nissen fundoplication in Cornelia de Lange syndrome spectrum: Who are the potential candidates?

Am J Med Genet A. 2020 Jul;182(7):1697-1703. doi: 10.1002/ajmg.a.61625. Epub 2020 May 21.

Abstract

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.

Keywords: Cornelia de Lange spectrum; Nissen fundoplication; gastroesophageal reflux disease; proton pump inhibitors.

MeSH terms

  • Adolescent
  • Adult
  • Cell Cycle Proteins / genetics
  • Child
  • Child, Preschool
  • De Lange Syndrome / complications
  • De Lange Syndrome / genetics*
  • De Lange Syndrome / surgery*
  • Female
  • Fundoplication
  • Gastroesophageal Reflux / drug therapy
  • Gastroesophageal Reflux / etiology
  • Gastroesophageal Reflux / surgery*
  • Humans
  • Infant
  • Intellectual Disability / etiology
  • Male
  • Mutation
  • Retrospective Studies
  • Young Adult

Substances

  • Cell Cycle Proteins
  • NIPBL protein, human