Developmental variation in second-to-fourth digit ratio (2D:4D) in children with cerebral palsy: an exploratory
Ayşe Gülşen Doğan1, Pınar Özge Başaran1, Pınar Koç2
1Department of Physical Medicine and Rehabilitation, Hitit University Faculty of Medicine, Türkiye.
Objective:
Cerebral palsy (CP) is an etiologically heterogeneous neurodevelopmental condition arising from disturbances of the developing brain during prenatal, perinatal, or early postnatal life. The second-to-fourth digit ratio (2D:4D) has been proposed as an imperfect indirect correlate of first-trimester prenatal sex-steroid exposure. This study aimed to compare 2D:4D ratios between children with CP and healthy controls and to examine whether digit ratio was associated with functional and clinical severity in children with CP.
Methods:
This case-control, cross-sectional study included 75 children with CP aged 4-12 years and 75 age- and sex-matched healthy controls. Second and fourth digit lengths were measured on both hands using a digital caliper, and right and left 2D:4D ratios were calculated. Gross motor function, manual ability, and spasticity were evaluated using the Gross Motor Function Classification System, Manual Ability Classification System, and Modified Ashworth Scale, respectively. Group comparisons, sex-stratified analyses, two-way analysis of variance, and correlation analyses were performed.
Results:
The CP and control groups were comparable in age and sex distribution. Children with CP had significantly lower right and left 2D:4D ratios than controls. Females showed higher 2D:4D ratios than males, independent of group. No significant group × sex interaction was observed. The 2D:4D ratio was not significantly correlated with GMFCS, MACS, or MAS scores. Clinical severity measures were significantly interrelated.
Conclusion:
Children with CP showed lower 2D:4D ratios in both hands than healthy controls, whereas digit ratio was not associated with functional severity or spasticity. These exploratory findings suggest that 2D:4D variation may be associated with heterogeneity in the timing of prenatal influences related to CP. However, because neither prenatal sex-steroid concentrations nor the timing of prenatal perturbations was directly measured, no specific hormonal or temporal mechanism can be inferred.

