Cornelia de Lange syndrome type 4 with a novel heterozygous missense variant in RAD 21 gene

Cornelia de Lange syndrome (CdLS) is a congenital multisystemic disorder characterized by genetic heterogeneity. It presents with features such as growth and cognitive retardation, upper limb deformities, cardiac, ophthalmologic, and genitourinary anomalies, alongside distinctive facial characteristics. The CdLS phenotype represents a spectrum that includes both classic and non-classic phenotypes resulting from pathogenic variants in genes associated with cohesin functioning, including NIBPL, SMC1A, SMC3, RAD21, BRD4, HDAC8, and ANKRD11. Mutations in these genes manifest diverse clinical features, with RAD21 variants accounting for a small percentage of cohesinopathies in humans. RAD21-related cohesinopathy typically exhibits growth retardation, minor skeletal anomalies, and facial features overlapping with CdLS. However, cognitive involvement tends to be milder. Despite this, due to the limited number of reported cases with RAD21 mutations, establishing genotype-phenotype correlations remain challenging. We present the case of an 18-month-old boy exhibiting developmental delay and distinct morphological features including micro-brachycephaly, depressed nasal bridge, upturned nose, long philtrum, low-set ears, mesomelic limb dwarfism, and a complete endocardial cushion defect. Exome sequencing revealed a novel RAD21 variant in this individual.