J Med Genet.

BACKGROUNDEllis-Van Creveld (EVC) syndrome is one of the entities belonging to the skeletal ciliopathies short rib-polydactyly subgroup. Major signs are ectodermal dysplasia, chondrodysplasia, polydactyly and congenital cardiopathy, with a high degree of variability in phenotypes ranging from lethal to mild clinical presentations. The and genes are the major genes causative of EVC syndrome. However, an increased number of genes involved in the ciliopathy complex have been identified in EVC syndrome, leading to a better understanding of its physiopathology, namely, , , , , and . They all code for proteins located in the primary cilia, playing a key role in signal transduction of the Hedgehog pathways.METHODSThe aim of this study was the analysis of 50 clinically identified EVC cases from 45 families to further define the phenotype and molecular bases of EVC.RESULTSOur detection rate in the cohort of 45 families was of 91.11%, with variants identified in (77.8%), (6.7%), (2.2%), (2.2%) or (2.2%). No distinctive feature was remarkable of a specific genotype-phenotype correlation. Interestingly, we identified a high proportion of heterozygous deletions in of variable sizes (26.92%), mostly inherited from the mother, and probably resulting from recombinations involving Alu sequences.CONCLUSIONWe confirmed that and are the major genes involved in the EVC phenotype and highlighted the high prevalence of previously unreported CNVs (Copy Number Variation).KEYWORDSBone Diseases, Endocrine, Diagnosis, Human Genetics© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.