WNT10A, dermatology and dentistry

Abstract

WNTs (Wingless-related integration sites) are secreted glycoproteins that are involved in signalling pathways critical to organ development and tissue regeneration. Of the 19 known WNT ligands, one member of this family, WNT10A, appears to have specific relevance to skin, its appendages and teeth. This review focuses on how variants in the WNT10A gene have been associated with various ectodermal disorders and how such changes may have clinical relevance to dermatologists and dentists. Germline mutations in WNT10A underlie several forms of autosomal recessive ectodermal dysplasia in which heterozygous carriers may also display some lesser ectodermal anomalies. Within the general population, multiple heterozygous variants in WNT10A can cause skin, hair, sweat gland or dental alterations, also known as ectodermal derivative impairments. WNT10A variants have also been implicated in hair thickness, male androgenetic alopecia, hair curl, acne vulgaris, lipodystrophy, keloids, wound healing, tooth size, tooth agenesis, hypodontia, taurodontism and oral clefting. Beyond dermatology and dentistry, WNT10A abnormalities have also been identified in kidney fibrosis, keratoconus, certain malignancies (particularly gastrointestinal) and neuropathic pain pathways. In this review, we detail how WNT10A is implicated as a key physiological and pathological contributor to syndromic and nonsyndromic disorders, as well as population variants, affecting the skin and teeth, and document all reported mutations in WNT10A with genotype-phenotype correlation.