Clinical Characteristics, Genetic Analysis, and Literature Review of Cornelia de Lange Syndrome Type 4 Associated With a RAD21 Variant

Abstract

ABSTRACT Background Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants. Methods A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole‐exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing. Results A 13.3‐year‐old male patient with a height of 136.5 cm (−3.5 SDS) and a weight of 28.4 kg (−3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients. Conclusion This study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum.

Keywords

• Cornelia de Lange syndrome type 4
• RAD21
• short stature
• whole‐exome sequencing