Finger bone immaturity and 2D:4D ratio measurement error in the assessment of the hyperandrogenic hypothesis for the etiology of autism spectrum disorders

Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of autism spectrum disorders (ASD). The ratios of the lengths of the bones of the 2nd to the 4th digit (2D:4D) are purported to be markers for prenatal androgen exposure and to be established early in gestation. Elongation of the 4th digit in response to testosterone is said to reduce 2D:4D in males versus females. We examined the ratios of bones from the left hand radiographs of 75 boys and 6 girls 4–8 years of age, diagnosed with ASD, to evaluate digit ratio as a marker for gestational androgen exposure. Contrary to our expectations, girls had reduced 2D:4D compared to boys but the difference was not significant (Cohen's D 0.51–0.66, P > 0.05). The limited sample size for this study and the absence of a referent group precluded providing robust estimates for girls and identifying possible statistical differences between the sexes. Tanner–Whitehouse 3 (TW3) rating of finger bone growth suggested relative immaturity of the 4th relative to the 2nd digits. Positive correlations were detected for 2D:4D ratios, body mass index (r = 0.23, P = 0.039), chronologic age (r = 0.35, P = 0.001), and skeletal age (r = 0.42, P < 0.0001). The TW3 ratings and associations between 2D:4D ratios and indicators of growth suggest that digits develop at different rates. This asynchronous development may produce differences in 2D:4D over time which could lead to erroneous interpretation of androgen exposure in utero among young ASD children.