Psychometric Validation of a Clinician-Reported Clinical Severity Assessment in STXBP1-Related Disorder
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AIM
STXBP1-related disorder (STXBP1-RD) is a severe developmental and epileptic encephalopathy characterized by early-onset seizures and persistent cognitive and motor impairments. With disease-modifying trials emerging, a disorder-specific severity scale is needed. To address this, we adapted a validated clinician-reported measure from CDKL5 Deficiency Disorder to develop the STXBP1 Clinical Severity Assessment (S-CSA) and evaluated its psychometric properties.
METHOD
The S-CSA was adapted from the CDKL5 Clinical Severity Assessment through expert consensus sessions with STXBP1 clinicians. Revisions addressed gaps in motor and vision domains, adding tremor and vision items. The measure was administered to 123 individuals with STXBP1-RD. Psychometric evaluation included confirmatory factor analysis, internal consistency, composite reliability, average variance extracted, and distinctiveness, compared with recommended thresholds.
RESULTS
Analyses supported a three-domain structure (motor, communication, vision) with factor loadings >0.5 and strong internal consistency (Cronbach’s alpha >0.7; composite reliability >0.88). Model fit and variance metrics met recommended standards, and domains demonstrated distinctiveness. No ceiling or floor effects were observed. Minimal skew was seen in motor (0.34) and communication (−0.16) domains; positive skew in vision (2.2) was seen, identifying patients with and without cortical visual impairment.
INTERPRETATION
The S-CSA demonstrates strong validity and reliability in STXBP1 -RD and may show utility in clinical trials for STXBP1 -RD and potentially other severe DEEs.
What this paper adds
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First disorder-specific clinician-reported severity scale developed for STXBP1 -RD.
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Demonstrated strong reliability and validity across three core domains.
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S-CSA has now shown content and psychometric validity.
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S-CSA may be a useful endpoint for upcoming STXBP1 clinical trials.
