Feasibility and Validity of Clinical Outcome Measures in a Prospective Natural History Study of STXBP1-Related Disorders

Aims: To describe the developmental phenotype of individuals with STXBP1-related disorders (STXBP1-RD) in a prospective natural history study using standardized outcome measures. Methods: Data were collected from 155 individuals with a mean age of 8.2 years. The Bayley Scales of Infant and Toddler Development-Fourth Edition (Bayley-4), Hand Manipulation and Eye Hand Coordination subtests of the Peabody Developmental Motor Scales-Third Edition (PDMS-3), and Gross Motor Function Measure-66 (GMFM-66) were assessed. The Gross Motor Function Classification System (GMFCS), Mini-Manual Ability Classification System (MiniMACS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) were used to classify participants. Results: Assessments were well tolerated with 0-6.9% incomplete assessments. Floor or ceiling effects were not common with raw scores, age equivalents, or growth scales values but were frequently observed with scaled scores. Significant differences were found between the Bayley-4, GMFM-66, and PDMS-3 when participants were divided into groups by corresponding developmental domain classification scale. Strong associations (p < 0.05) were seen between all measures across Bayley-4 domains, PDMS-3 domains, and GMFM-66 total scores. Interpretation: The Bayley-4, GMFM-66, and PDMS-3 are suitable for use in clinical practice and future clinical trials in STXBP1-RD.