Associations between long-term hair cortisol levels and executive functioning in Wiedemann-Steiner Syndrome

Wiedemann-Steiner syndrome (WSS) is a neurodevelopmental disorder caused by pathogenic KMT2A variants and characterized by intellectual disability, behavioral challenges, and executive dysfunction. KMT2A loss has been linked to atypical neurogenesis in hippocampal and prefrontal regions, potentially contributing to dysregulated behaviors. Endocrinological abnormalities have also been found among those with WSS, which in turn may impact their stress biology. This study examines the associations between chronic stress, measured by hair cortisol concentration (HCC), and cognitive and behavioral functioning in WSS.

Twenty White individuals with WSS (14 female; M_age = 14.85 years, SD = 6.14) completed standardized tests of executive functioning. Caregivers completed the Behavior Rating Inventory of Executive Function and the Child/Adult Behavior Checklist to index daily behavior functioning. Hair samples were collected from participants and their parents to derive HCC.

Mean HCC levels in the subset of children with WSS did not differ from normative reference values. In our whole cohort, higher HCC was associated with poorer performance scores on tests of cognitive flexibility. Regression models showed that higher HCC predicted poorer cognitive flexibility, explaining 36%-42% of the variance.

These findings provide preliminary evidence that long-term cortisol levels are related to performance-based executive functioning difficulties in WSS. Results within the context of extant literature on WSS suggest that altered stress physiology, such as chronic exposure to stress hormone production, may contribute to their executive and behavioral dysfunction, potentially reflecting the downstream impact of disrupted KMT2A epigenetic function on later functional development of the prefrontal lobe network. (PsycInfo Database Record (c) 2026 APA, all rights reserved).