Minor physical anomalies in ASD and ADHD: a systematic review and meta-analysis

Minor physical anomalies (MPAs) are subtle morphological variants that may reflect atypical prenatal development. Elevated MPAs have been reported in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but findings have been inconsistent.

We systematically searched PubMed, Web of Science, and grey-literature sources for case-control studies published through December 2025 that reported total MPA scores in ASD or ADHD versus typically developing controls. Pooled effect sizes were calculated as Hedges' g using random-effects models with restricted maximum likelihood estimation. Shared control groups were handled by sample splitting. Heterogeneity, subgroup and moderator effects, and small-study effects were examined.

Twelve ASD studies and eight ADHD studies met inclusion criteria. Across disorders, MPAs were significantly elevated relative to controls (pooled g = 0.72, 95% CI 0.56-0.89). Disorder-specific pooled estimates were significant for both ASD (g = 0.69) and ADHD (g = 0.77), with no significant difference between disorders (Q_bet = 0.22, p = 0.64). In ASD, effects were stronger for craniofacial anomalies than for peripheral anomalies, and item-level syntheses highlighted several ear- and palate-related features. In ADHD, evidence of small-study effects suggested possible overestimation, although conclusions remained robust in sensitivity analyses.

MPAs are reliably elevated in both ASD and ADHD. Current case-control evidence supports MPAs as a transdiagnostic marker of early developmental perturbation rather than a feature that strongly differentiates between these disorders.