Psychometric validation of a clinician-reported clinical severity assessment in STXBP1-related disorder

To adapt a validated clinician-reported measure from CDKL5 deficiency disorder for use in STXBP1-related disorders and evaluate the psychometric properties of the resulting STXBP1 Clinical Severity Assessment (S-CSA).

In this multicenter, prospective, natural history study, the S-CSA was adapted from the CDKL5 Clinical Severity Assessment through expert consensus sessions with STXBP1 clinicians. Revisions addressed gaps in the motor and vision domains, adding tremor and vision items. The measure was administered to 123 individuals with STXBP1-related disorders (50% males, median age 7 years 8 months). Psychometric evaluation included confirmatory factor analysis, internal consistency, composite reliability, average variance extracted, and distinctiveness, compared with recommended thresholds.

Analyses supported a three-domain structure (motor, communication, vision) with factor loadings greater than 0.5 and strong internal consistency (Cronbach's alpha >0.7; composite reliability >0.88). Model fit and variance metrics met the recommended standards, and domains demonstrated distinctiveness. No ceiling or floor effects were observed. Minimal skew was seen in the motor (0.34) and communication (-0.16) domains; positive skew in vision (2.2) was observed, identifying patients with and without cortical visual impairment.

The S-CSA demonstrates strong validity and reliability in STXBP1-related disorders and may show utility in clinical trials for STXBP1-related disorders and potentially other severe developmental and epileptic encephalopathies.