Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVCgene

Abstract

Abstract Background Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance. Methods Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the EVC/EVC2 locus. The results did not exclude linkage, so samples were sequenced for mutations. Results We identified a c.1868T>C mutation in EVC, which predicts p.L623P, and was homozygous in affected individuals. Conclusion We conclude that this EVC mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. EVC mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.