Ellis‐van Creveld syndrome: Report of a case and recurrent variant

Abstract Background Ellis‐van Creveld syndrome (EvCS) is a rare autosomal recessive skeletal dysplasia that is characterized by short stature, short limbs, short ribs, polydactyly and structural heart defect. Despite locus heterogeneity, in the majority of the cases, the disorder segregates with mutations in the EVC and EVC2 genes, notably mutations with truncating protein as a final sequence. In the present study, we report the prenatal findings and genetic analysis of a terminated pregnancy affected by severe thoracic and skeletal dysplasia. Methods After detailed physical and clinical examination, whole exome sequencing (WES) was performed and the variant was confirmed by Sanger sequencing. Results One homozygote variant in EVC2 gene was identified in the fetus (NM_147127, c.942G>A, p.W314X). The EVC2 gene is strongly associated with EvCS, which is consistent with the sonographic findings of the fetus. Conclusions The homozygous p.W314X mutation found in this family was recently reported to be segregated in a consanguineous family originating from Pakistan. The occurrence of the p.W314X mutation in two unrelated families (Iranian and Pakistani) may be the result of an old founder effect or arose because of a mutational hotspot and is supporting evidence for the pathogenicity of this variant. Because skeletal dysplasia belongs to a broad spectrum of syndromes and therefore exhibits considerable background locus and allelic heterogeneity, our report highlights the need for appropriate genetic counseling and supports the feasibility of WES to determine an accurate diagnosis, as well as precise recurrence risk prediction.