Association between head circumference and 2D:4D finger ratios in children and adolescents with autism spectrum disorders

Macrocephaly and the second-to-fourth digit ratio (2D:4D), a non-invasive proxy for prenatal androgen exposure, are independent biomarkers associated with Autism Spectrum Disorder (ASD). However, the utility of combining these two distinct biological markers as a composite risk factor has not yet been investigated. This descriptive, observational, cross-sectional study included 144 children and adolescents (82% male) with ASD, with measurements of head circumference and finger length for both hands. Correlation, chi-square, and linear regression analyses were conducted to examine associations. Contrary to the traditional Extreme Male Brain hypothesis, we found a significant association between the co-occurrence of macrocephaly and a high (feminized) 2D:4D finger ratio within our cohort. Interestingly, females showed a strong positive correlation between head circumference and the left-hand 2D:4D ratio (rho = 0.629, p = 0.011). Linear regression confirmed that a more feminized left-hand 2D:4D ratio robustly predicts larger head circumference in girls with ASD, explaining 68.08% of the variance. We propose the co-occurrence of macrocephaly and a high 2D:4D ratio as a novel endophenotype for ASD. Our findings support an integrated neurodevelopmental model in which accelerated head growth may be driven by a distinct steroid imbalance, potentially involving maternal estriol (E3) and environmental endocrine disruptors (BPA). This offers a specific, quantifiable, and non-invasive marker for a biologically heterogeneous subgroup within ASD.