Endocrine Abstracts

JOINT1264

Background: Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder characterized by a range of developmental and physical anomalies. This study aims to evaluate the clinical characteristics and genetic variations in 20 pediatric patients diagnosed with CdLS.

Methods: We compared clinical characteristics of 20 patients grouped by genotypes based on whole exon sequencing and performed subgroup analyses according to the presence or absence of null variants.

Results: Comprehensive clinical evaluations revealed that 70% of the patients experienced prenatal growth retardation and short stature, while 85% exhibited global developmental delays. Craniofacial dysmorphisms, such as synophrys, short noses, and anteverted nares, were highly prevalent, observed in up to 90% of the cohort. Additional manifestations included skeletal abnormalities (80% exhibited small hands and/or feet), skin manifestations (30% with hirsutism or mottled skin), and sensory impairments (20% with hearing loss). Genetic analysis identified variants in the NIPBL (75%), SMC1A (15%), and RAD21 (10%) genes. Null mutations, which result in complete loss of protein function, were significantly associated with the classical CdLS phenotype and corresponded with more severe clinical manifestations, including heightened intellectual disability. Three patients received growth hormone treatment, displaying diverse responses.

Conclusions: Our findings underscore the heterogeneity of clinical presentations in CdLS and emphasize the critical role of the mutation type in determining disease severity. These results warrant further investigations to optimize management strategies and improve understanding of the functional significance of the identified variants.