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.