Clinical and Molecular Findings in 17 Patients with Cornelia de Lange Syndrome: Four Novel Variants and an ANKRD11 Gene Variant.

Introduction: Cornelia de Lange syndrome is a rare congenital malformation syndrome characterized by prenatal-onset growth retardation, with typical facial findings that include bushy eyebrows, synophrys, long and thick eyelashes, ptosis, anteverted nostrils, long philtrum, and thin and downward sloping vermilion. The syndrome is caused by mutations in NIPBL, SMC1A, SMC3, RAD21, HDAC8, and ANKRD11 genes encoding cohesin complex proteins that maintain a chromatin structure in cell proliferation. In recently reported cases, new genes that are not involved in the cohesin complex but clinically cause CdLS have been identified. With these newly identified genes, the term chromatinopathies has been offered for this syndrome as it is more inclusive. Patients with the syndrome are classified as classical CdLS or CdLS-like phenotype according to their clinical features. Methods: The clinical and molecular results of 17 new cases of CdLS are reported. Results: The patients, who were between 2 months and 12 years of age, all had unique facial findings as well as growth retardation. Congenital malformations accompanying the syndrome in the patients were different. The molecular analysis showed genetic etiology in 13 patients, of which 2 were deletions and 11 were pathogenic missense variants in the NIPBL, HDAC8, and SMC1A genes and of these variants, some had not been reported previously. Conclusion: By presenting the clinical and molecular results of these CdLS cases, it was aimed to expand the clinical spectrum, contribute to a better understanding of the genotype-phenotype relationship, and highlight the importance of molecular methods used in the diagnosis of genetic diseases.