Quantitative deep motor phenotyping of 102 people with SCN2A, KCNQ2, CSNK2A1, CACNA1A or SCN8A-related disorders

In 102 pediatric-onset monogenic NDD patients with SCN2A, KCNQ2, CSNK2A1, CACNA1A, or SCN8A variants, motor dysfunction is common and SCN2A shows higher, consistent z-scores in coordination and speech.

• Why it matters: Motor impairment drives disability, but motor outcomes in clinical trials are limited by mostly categorical descriptions rather than quantified, domain-specific severity across development.
• What they did: This cross-sectional observational study (0.5–38 years) used the Scale for Assessment and Rating of Ataxia, Burke-Fahn-Marsden Dystonia Scale, and Modified Ashworth Scale in 102 affected individuals and 31 unaffected sibling controls, with gene-specific z-score standardization and bootstrap 95% confidence intervals.
• The result: Dysfunction was present in speech (90%), coordination (87%), dystonia (83.3%), gross motor (82.4%), and spasticity (42.2%) versus minimal control impairment (0–12.9%); SCN2A coordination mean z = 0.29 (95% CI 0.03–0.54) and speech mean z = 0.3 (95% CI 0.03–0.57), supporting quantitative motor endpoints.

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