Clinical delineation and genotype-phenotype correlation of 84 pediatric patients with Cornelia de Lange syndrome: insights from a single-center Chinese study.

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder, which has clinical and genetic heterogeneity. This study investigated the clinical and genetic characteristics of a large cohort of CdLS in China and elucidated genotype-phenotype correlations. The clinical manifestations, laboratory tests, and genetic testing of pediatric participants from January 2011 to December 2025 were retrospectively analyzed. We compared clinical phenotypes of patients with NIPBL variants versus those with variants in other causative genes, as well as among patients with different types of NIPBL variants. A total of 84 Chinese patients diagnosed with CdLS were included in this cohort. Growth curve analysis delineated distinct sex-specific patterns. Male patients experience severe growth faltering during puberty, suggesting an underlying deficit in sex hormone drive. This is further corroborated by the significant growth acceleration achieved with hormone replacement therapy in a male patient diagnosed with hypogonadotropic hypogonadism. NIPBL variants were the predominant cause, accounting for 66.7% of cases, and correlated with the most severe phenotypic spectrum. Notably, this subgroup exhibited significantly more severe growth retardation and a higher frequency of classic facial features (p < 0.001). Furthermore, severe upper limb deformities, such as oligodactyly, were identified exclusively in the NIPBL subgroup.

Conclusion

This study characterized a Chinese CdLS cohort, establishing its first growth curves and observing a positive growth response to hormone therapy. Our findings confirm the link between NIPBL variants and the most severe phenotype, thereby underscoring the necessity of a genotype-stratified approach for clinical management and counseling.