What the study measured
Wolswijk and colleagues at Frisius Medical Center Leeuwarden asked a narrow, answerable question: how common is mandibular tooth agenesis in people with a nonsyndromic orofacial cleft compared with people without one. The design was a retrospective single-center case-control study using panoramic radiographs. The study group comprised 232 individuals with cleft lip, cleft lip and palate, or cleft palate under treatment by Cleft Team North; the control group comprised 350 individuals without an orofacial cleft from the Department of Oral and Maxillofacial Surgery. Agenesis was scored per individual and per tooth element using the Tooth Agenesis Code.
What the numbers show
Mandibular agenesis was present in 10.3% of the cleft group and 4.9% of the control group (P = .013). The elevation was not uniform across cleft types. In cleft palate only, agenesis was four times more prevalent than in controls (16.4%, P = .005). In cleft lip and palate it was 9.4%, roughly double the control rate, at the edge of significance (P = .063). In cleft lip only, there was no mandibular agenesis at all. The mandibular second premolar was the most frequently missing tooth in both groups, with the left second premolar more often absent in cleft lip and palate and in cleft palate, and the right second premolar more often absent in cleft palate only. Unilateral and bilateral cleft lip and palate showed corresponding agenesis locations. The authors conclude that mandibular agenesis appears to be part of the cleft lip and palate and cleft palate phenotype, implying shared developmental pathways between orofacial clefting and tooth agenesis.
Why it matters for regeneration programmes
This is epidemiology, not an intervention, so it does not sit on the T1 to T5 ladder we use at /method/ to grade therapies. What it does is define the terrain on which agenesis therapies would operate. The lead whole-tooth programme we track, the anti-USAG-1 antibody TRG-035 at /programs/anti-usag-1-trg035/, holds Japanese orphan drug designation for severe congenital partial anodontia and plans its Phase II efficacy work in children with congenital agenesis. Papers like this one sharpen the picture of who those patients are: agenesis clusters with specific cleft subtypes, favors specific teeth, and tracks the side of the cleft. Any future efficacy readout for a tooth-induction drug will need exactly this kind of baseline prevalence and patterning data to choose sites and endpoints credibly.
Where we differ from the coverage
Agenesis papers are routinely folded into “regrowing teeth” coverage as if each new prevalence study were progress toward a treatment. It is not. This study changes no therapy, tests no drug, and recruits no one. Its honest contribution is narrower and still useful: a shared developmental pathway between clefting and missing teeth, and a well-measured control rate (4.9%) against which future claims about agenesis populations can be checked.
Provenance: every claim above traces to the published abstract of Wolswijk et al., The Cleft Palate Craniofacial Journal (2026), per our method at /method/.