Defects in the WDR35 gene are associated with various disorders known as ciliopathies. This include Sensenbrenner syndrome (known as cranioectodermal dysplasia, CED), short-rib thoracic dysplasia with or without polydactyly (SRTD7). SRTD group of disorders encompasses Ellis-van Creveld syndrome (EvC), Asphyxiating thoracic dystrophy (JATD) and Mainzer-Saldino syndrome (MZSDS). Variants in this gene have also been described in patients with EvC and JATD. Ciliopathies are a heterogenous group of diseases that affect multiple systems within the body (e.g. kidney, liver, heart, eye, brain, lungs, and skeleton), and are caused by defective cilia function and/or structure. Disorders associated with WDR35 variants are inherited in an autosomal recessive manner and are multisystem diseases characterized by short stature, dolichocephaly, epicanthus, narrow chest, limb shortening, brachydactyly, postaxial polydactyly, syndactyly, and ectodermal abnormalities (small teeth, dental fusion, sparse eyebrows). Renal insufficiency is a common feature that can lead to end-stage renal disease (ESRD) in infancy/childhood and require a renal transplantation. ESRD is a major cause of morbidity and mortality in affected individuals. Liver disease, retinal dystrophy, and intellectual disability might be also present in patients with WDR35 changes.
Prevalence: CED2, SRDT7 (including EvC and JATD ) are rare disorders. The exact frequency is unknown. To date fewer than 100 patients with WDR35 variants have been described in the literature.
WDR35