Clinical and molecular findings in Cornelia de Lange syndrome. Case series

Abstract

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder caused by pathogenic variants in genes related to the regulation of cohesin transcription. It presents a very heterogeneous clinical phenotype, with wide variability in severity.

Objective: To describe the clinical and molecular findings in patients diagnosed with CdLS.

Patients and Method: Observational and descriptive study conducted in patients with CdLS evaluated between April 1, 2020, and April 1, 2024, at the Clinical Genetics Unit, Pediatrics Service, of the Hospital Regional de Antofagasta. The diagnostic algorithm suggested by the first international consensus statement for CdLS was used, and the results of the genetic studies were analyzed.

Results: Six patients aged 0–17 years were included; 4 were male. Global developmental delay and/or intellectual disability, the presence of synophrys, abnormalities of the nose and lips, and hypertrichosis were confirmed in all patients. Heterozygous variants in the NIPBL gene were found in 5/6 patients (83.33%), all classified as pathogenic and associated with cases of classic CdLS. Four of the variants described in this study have not been previously reported in the literature.

Conclusions: Neurological alterations, facial dysmorphism, and hypertrichosis were present in all patients studied. Heterozygous pathogenic variants in the NIPBL gene represented the main etiopathogenic cause, allowing for timely family genetic counseling.