Wnt10a

WNT10A is a gene that encodes a member of the Wnt family of secreted signaling proteins. Wnt-10a participates in the canonical Wnt/β-catenin signaling pathway, which regulates development and cell fate decisions in multiple tissues, including teeth, nails, skin, and hair. The gene is expressed in dental epithelium during tooth formation and is involved in odontogenesis and the formation of ectodermal structures.

Pathogenic variants in WNT10A are a major cause of tooth agenesis, including hypodontia (missing a few teeth) and oligodontia (missing many teeth). The phenotypic spectrum ranges from nonsyndromic tooth agenesis to syndromic conditions that involve ectodermal abnormalities. The most well-described syndromic association is odonto-onycho-dermal dysplasia (OODD), which features dental anomalies along with nail, hair, and skin abnormalities due to defects in ectodermal development. In many cases, individuals with WNT10A mutations may present with nonsyndromic tooth agenesis without other ectodermal features. Inheritance is typically autosomal recessive for syndromic cases, with variable expressivity and penetrance.

Mechanistically, WNT10A encodes a lipid-modified secreted glycoprotein that binds Frizzled receptors to activate the canonical Wnt signaling pathway, influencing tooth morphogenesis and maintenance of ectodermal tissues. Genetic testing, including sequencing of WNT10A, is used in the evaluation of tooth agenesis and suspected ectodermal dysplasias. Management is primarily dental-focused, with prosthetic or restorative options, while syndromic cases may require multidisciplinary care for skin, nails, and hair abnormalities.