Association of the Disheveled 2 (DVL2) Gene c.2044delC Variant with Increased Risk of Canine Cleft Palate

Canine congenital cleft palate is one of the most common craniofacial anomalies in dogs, characterized by a failure of the palatal shelves to fuse properly during fetal development, leading to abnormal communication between the oral and nasopharyngeal cavities. Patients with cleft palate can experience significant challenges including feeding difficulties, aspiration pneumonia, and respiratory distress, all of which can profoundly impact quality of life and, in severe cases, survival. The clinical management of cleft palate in dogs involves a combination of medical and surgical interventions. The aim of this study was to identify common genomic variants associated with cleft palate. A GWAS with 266 cases ascertained from a general population of more than 1 million dogs attending primary care veterinary clinics in the United States was used to identify an association in the region of the disheveled 2 (DVL2) gene variant c.2044delC, previously linked to Robinow-like syndrome and the screw tail phenotype in Bulldogs and related breeds. The association was confirmed through genotyping of the DVL2 variant. In summary, this study identifies the DVL2 variant that is fixed and breed defining in several breeds as a risk factor for cleft palate in dogs.