INTRODUCTION
Ellis-van Creveld (OMIM #225500) syndrome, which is also known as chondroectodermal dysplasia is a infrequent autosomal recessive skeletal dysplasia which is characterized by polydactyly, ectodermal dysplasia, chondrodysplasia and congenital cardiac abnormalities. It was first identified by Richard Ellis and Simon van Creveld in three children with chondrodysplasia, polydactyly and oral abnormalities1. Although the exact prevalence of this disease is not known, it is estimated as 7/1,000,000 in non-Amish population2,3
Short stature, thoracic hypoplasia, postaxial polydactyly, abnormalities in dental structures with varying severity such as peg-shaped teeth, natal teeth and abnormalities in enamel, dysplastic nails, sparse hair and multiple frenulum can be observed in patients with Ellis-van Creveld (EvC) syndrome. In addition, approximately %60 of EvC syndrome patients have congenital heart defects which affect their prognose. The most common cardiac malformations are atrioventricular septal defect (AVSD) and single atrium. Cognitive and motor development is generally preserved4,5 .
EvC syndrome is mostly associated with biallelic variations in two genes; EVC (EvC ciliary complex subunit 1, OMIM 604831) andEVC2 (EvC ciliary complex subunit 2, OMIM 607261). Localized at 4p16.2, EVC and EVC2 encode ciliar basal body proteins with 21 and 22 exons, respectively. Thus, EvC is also defined as primary ciliopathy6. Rarely, biallelic mutations inDYNC2LI1 (Dynein, cytoplasmic 2, light intermediate chain 1),GLI1 (Gli family zinc finger 1) and WDR35 (Wd repeat-containing protein 35) have also been reported in EvC7-9. So far, nearly 25% of the EvC patients do not carry any genomic variation.
In this study, a novel homozygous variant, EVC2 c.3533_3546del (p.Glu1178Glyfs*82) is identified in a patient with EvC syndrome. This variant may interfere with Hedgehog (Hh) signaling pathways thus causing abnormalities in endochondral and skeletal development6,10.