Clinical and molecular characteristics of Korean children with Cornelia de Lange syndrome

ABSTRACT

Purpose@#Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder caused by genetic variants of the cohesin complex. However, the diverse genetic etiologies and their phenotypic correlations in Korean patients with CdLS are still largely unknown. Hence, this study aimed to clarify the clinical characteristics and genetic background of Korean patients with CdLS. @*Materials and Methods@#The medical records of 15 unrelated patients (3 males and 12 females) genetically confirmed to have CdLS were retrospectively reviewed. All individuals were diagnosed with CdLS using target gene analysis, whole-exome sequencing, and/or chromosomal microarray analysis. The clinical score (CS) was calculated to assess disease severity. @*Results@#The median age at diagnosis was 1.7 (range, 0.0-11.8) years, and median follow-up duration was 3.8 (range, 0.4-11.7) years. Eight (53.3%) patients showed classic phenotypes of CdLS, two (13.3%) showed non-classic phenotypes, and five (33.3%) had other phenotypes sharing limited signs of CdLS. Fifteen causative variants were identified NIPBL in five (33.3%, including 3 males), SMC1A in three (20.0%), SMC3 in three (20.0%), and HDAC8 in four (26.7%) patients. The CS was significantly higher in the NIPBL group than in the non-NIPBL group (14.2±1.3 vs. 8.7±2.9, P<0.001). @*Conclusion@#We identified the clinical and genetic heterogeneity of CdLS in Korean patients. Patients with variants of NIPBL had a more distinctive phenotype than those carrying variants of other cohesin complex genes (SMC1A, SMC3, and HDAC8). However, further studies are warranted to understand the pathogenesis of CdLS as a cohesinopathy and its genotype-phenotype correlations.