WDR35 variants in a cranioectodermal dysplasia patient with early onset end-stage renal disease and retinal dystrophy

Cranioectodermal dysplasia (CED) is rare heterogeneous condition. It belongs to a group of disorders defined as ciliopathies and is associated with defective cilia function and structure. To date six genes have been associated with CED. Here we describe a 4-year-old male CED patient whose features include dolichocephaly, multi-suture craniosynostosis, epicanthus, frontal bossing, narrow thorax, limb shortening, and brachydactyly. The patient presented early-onset chronic kidney disease and was transplanted at the age of 2 years and 5 months. At the age of 3.5 years a retinal degeneration was diagnosed. Targeted sequencing by NGS revealed the presence of compound heterozygous variants in the WDR35 gene. The variants are a novel missense change in exon 9 p.(Gly303Arg) and a previously described nonsense variant in exon 18 p.(Leu641*). Our findings suggest that patients with WDR35 defects may be at risk to develop early-onset retinal degeneration. Therefore, CED patients with pathogenic variation in this gene should be assessed at least once by the ophthalmologist before the age of 4 years to detect early signs of retinal degeneration.

Automated summary

Cranioectodermal dysplasia (CED) is a rare condition associated with various symptoms and complications such as craniosynostosis, retinal degeneration, and limb abnormalities. A study found that defects in the WDR35 gene may increase the risk of early-onset retinal degeneration in CED patients. Therefore, it is recommended that CED patients with pathogenic variations in the WDR35 gene undergo ophthalmologic evaluation before the age of 4 to detect early signs of retinal degeneration.