Three-Dimensional Gait Analysis in STXBP1-Related Disorder

STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. The aim of this study was therefore to quantitatively assess gait in participants with STXBP1-RD.

In this cross-sectional study, we included ambulatory participants aged 6 years or older with genetically confirmed STXBP1-RD. Instrumented 3D gait analysis (i3DGA) was performed to objectively quantify gait. Functional mobility was assessed with the Functional Mobility Scale (FMS) and Mobility Questionnaire 28 (MobQues28). Caregiver health-related quality of life was evaluated using the PedsQL-Family Impact Module (PedsQL-FIM). We explored associations between gait, functional mobility, STXBP1-variant type, and clinical features (ID, age at seizure onset, seizure frequency, and age at onset of independent walking). Correspondence between i3DGA and the Edinburgh Visual Gait Score (EVGS), an observational gait assessment, was investigated.

Nineteen participants were included. Compared with typically developing peers, participants with STXBP1-RD had significantly reduced walking speed, step length, and stride length. Gait patterns were highly variable, with the most frequent pattern being an externally rotated foot progression angle (FPA), present in 15 of 19 participants. At home, 94.12% of the participants (16/17) walked independently, yet community mobility was more variable: 70.59% (12/17) walked independently, 11.76% (2/17) with aid, and 17.65% (3/17) used a wheelchair, indicating increasing limitations with distance and environmental complexity. Earlier acquisition of independent walking strongly predicted later unassisted ambulation at the community level (p < 0.001). The median MobQues28 score was 57.14% and median PedsQL-FIM score was 60.42%, indicating a moderate level of mobility limitations and reduced health-related quality of life of caregivers. EVGS was highly positive correlated with i3DGA (p = 0.001).

Quantitative gait analysis in participants with STXBP1-RD demonstrates heterogenous kinematic deviations, with an externally rotated FPA emerging as the most common pattern. Age at independent walking was a clinically relevant predictor of later functional mobility. EVGS showed strong correspondence with i3DGA and may offer a more practical, semiquantitative assessment for broader use. These findings inform clinical decision making and guide the selection of scalable outcome measures for natural history studies and interventional trials.