Delayed tooth eruption as an early clinical indicator of genetical tooth agenesis: A family-based study of cases with whole-exome sequencing.

Delayed tooth eruption is frequently considered a benign developmental variation but may represent an early sign of genetically driven tooth agenesis. We evaluated a 22-month-old female presenting with markedly delayed eruption (only eight primary teeth) and a positive family history of ectodermal features. Given the inconclusive early radiographic findings, whole-exome sequencing (WES) was utilized. WES revealed the proband carried a heterozygous EDARADD variant (NM_080738:c.328G > T; p. Asp110Tyr). Subsequent familial segregation analysis identified an additional heterozygous WNT10A variant (NM_025216:c.637G > A; p. Gly213Ser) within the broader family. The EDARADD variant alone was associated with varying presentations from normal dentition to delayed eruption. Furthermore, the WNT10A variant alone correlated with distinct tooth agenesis, whereas their coexistence exacerbated the phenotype, resulting in severe agenesis and ectodermal features. This case demonstrates WES provides critical diagnostic insight when radiographic evaluation is inconclusive in young patients, facilitating precision dentistry.