Ellis-van Creveld syndrome (EvC) is a ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. We screened causative mutations in 8 Vietnamese EvC patients. All the patients had a congenital heart defect with atypical oral and/or skeletal abnormalities. One had compound heterozygous EVC2 mutations: a novel mutation c.769G>T-p.E177X in exon 6 inherited from father and a previously reported mutation c.2476C>T-p.R826X in exon 14 inherited from mother. The EVC2 mRNA expression level was significantly lower in the patient and her parents compared to controls. Another case had a novel heterozygous EVC mutation (c.1717C>G-p.S572X) in exon 12, inherited from his father. Of note, the mother without any EVC mutation on Sanger sequencing showed a lower expression level of EVC mRNA compared to controls. SNP array analysis revealed that the patient and mother had a heterozygous 16.4 kb deletion in EVC. Interestingly, this patient also had a heterozygous very rare variant in exon 9 of EFCAB7 (c.1171 T > C-p.Y391H), inherited from his father. Both patient and father had short chordae, a phenotype first described in EvC. This mutation located in ECH1 domain, which reportedly interacts with EVC2 Weyer peptide. We hypothesized that mutated EFCAB7 may modify Hedgehog signaling. Binding assay between wild-type/mutated ECH1 and Weyer peptide revealed that the amount of mutated ECH1 bound to Weyer was significantly higher than that of wild-type ECH1. In conclusion, we detected pathogenic mutations of EVC/EVC2 in Vietnamese EvC patients. Moreover, we found a mutation of EFCAB7, which changes the EFCAB7-EVC2 interaction in Hedgehog signaling regulation, a possible pathological mechanism of EvC.