Subtle signs, significant insights: Exploring the spectrum of phenotypes in classic Cornelia de Lange syndrome

Abstract

This letter presents a case of classic Cornelia de Lange Syndrome (CdLS) that highlights the often-overlooked milder phenotypic presentations associated with NIPBL missense variants. Our patient, a 16-year-old girl, was diagnosed with CdLS and mild Intellectual Developmental Disorder (IDD). Despite typical facial features and growth retardation, she exhibited high autonomy and relatively preserved cognitive function. Genetic analysis revealed a likely pathogenic missense variant in the NIPBL gene, contrasting with the more severe phenotypes typically linked to frameshift and nonsense mutations. This case underscores the need for broader diagnostic criteria for CdLS, particularly in individuals with milder developmental issues and distinctive facial features. Recognizing these subtler presentations can lead to timely interventions and improved outcomes. We hope this case encourages further discussion on the expanded phenotypic spectrum of classic CdLS.