Categories: Skeleton phene (incl. short stature & teeth) , Cardiovascular system phene , Craniofacial phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 618082 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Dominant

Disease-related: unknown

Key variant known: yes

Year key variant first reported: 2025

Species-specific name: syndromic cleft palate with pentalogy of Fallot and internal hydrocephalus

Molecular basis: Bolcato et al. (2025): Genetic analysis identified a missense variant in WDR33 (omia.variant:1814) that was heterozygous in both analyzed cases [Belgian Blue cross calves] and in an estimated 40% of the paternal gametes of the mosaic [Belgian Blue] founder, but absent in both dams and controls. ... The genetic findings were most consistent with a likely pathogenic dominant de novo mutation in WDR33 as the underlying cause of the observed congenital syndrome."

Clinical features: Bolcato et al. (2025) report two paternal half-sibling Belgian Blue cross calves with cleft palate (CP), "permanent recumbency, strabismus, tachycardia, and tachypnea. chocardiographic findings were consistent with tetralogy of Fallot associated with patent foramen ovale (pentalogy of Fallot)."

Pathology: Bolcato et al. (2025): "Necropsy examination [of Belgian Blue cross calves] identified hydrocephalus in addition to CP and confirmed the clinical diagnosis of pentalogy of Fallot."

Breed: Belgian Blue (Cattle) (VBO_0000139).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: