Ellis-van Creveld syndrome (EVC; MIM 225500) and Weyers acrofacial dysostosis (MIM 193530) are allelic disorders that share some clinical findings but differ in severity and pattern of inheritance. Ellis-van Creveld syndrome is an autosomal recessive disorder and is the more severe of the two. Typical findings associated with EVC include: short limbed mesomelic dwarfism, low iliac wings with spur like projections of the medial lateral aspects of the acetabuli, postaxial polydactyly of the hands and often feet with cone shaped epiphyses of the phalanges, fusion of the capitate and hamate, short dysplastic nails, short ribs, pectus carinatum, genu valgum, multiple oral frenula, neonatal teeth, dysplastic teeth, hypodontia, partial cleft lip, and genitourinary abnormalities. About 60% of patients with EVC are reported to have congenital heart defects, the most common defects are an atrial septal defect or an atrioventricular septal defect.

Weyers acrofacial dysostosis differs from EVC in that inheritance is autosomal dominant and patients are less severely affected. Patients with Weyers acrofacial dysostosis syndrome have mild short stature with postaxial polydactyly, dysplastic nails, hypodontia with dysplastic teeth, neonatal teeth and multiple frenula. Individuals do not have cardiac abnormalities or short ribs.

Mutations in the EVC and EVC2 genes have been described in both EVC and Weyers acrofacial dysostosis patients. The EVC and EVC2 genes are nonhomologous genes arranged in a head-to-head manner. The transcription start sites are separated by approximately 2.6 kb. The function of these genes is unknown. It has been demonstrated that sequencing of the EVC and EVC2 genes identifies a mutation in approximately two-thirds of EVC patients. This suggests that there is genetic heterogeneity.

It should be noted that the EVC phenotype is variable. For example, some individuals with a homozygous EVC mutation were reported to have features similar to Ellis-van Creveld syndrome including short stature, postaxial polydactyly, septal defects and hypodontia. However, these individuals did not meet the full clinical presentation of the syndrome because they had a normal chest size and no upper lip defects. In addition, these patients had rhizomelic rather than mesomelic limb shortening.

Copy number variation (CNV) analysis of the Ellis-van Creveld syndrome and Weyers acrofacial dysostosis genes is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS and CNV panels) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests unless otherwise indicated.