KIF1A ‐Associated Neurological Disorder ( KAND ): Spectrum of Movement and Motor Disorders in a Cohort of 51 Patients

BACKGROUND: KIF1A-associated neurological disorder (KAND) encompasses a broad neurodevelopmental and neurodegenerative spectrum in which motor and movement disorders are common but incompletely defined. OBJECTIVES: To systematically characterize motor and movement disorder phenotypes in KAND. METHODS: In this cross-sectional study, 51 individuals with likely-pathogenic or pathogenic KIF1A variants underwent standardized neurological assessment using the Spastic Paraplegia Rating Scale (SPRS), SPATAX disability scale, Gross Motor Function Classification System (GMFCS), and Modified Ashworth Scale. RESULTS: A history of global developmental delay was present in 96.1% and neonatal or infantile hypotonia in 62.7%. Progressive spasticity occurred in 72.5%, predominantly affecting the lower extremities and correlated with age (β = 0.45, odds ratio [OR] = 1.56, 95% confidence intervals [95% CI] 1.09-2.25, P = 0.016). Lower extremity weakness was nearly universal (88.2%) and inversely related with age (β = -0.08, OR = 0.93, 95% CI 0.86-0.99, P = 0.032). Independent walking was achieved by 62.7% at a median age of 24 months, but only 31.4% retained independent ambulation at last evaluation. Movement disorders included motor stereotypies (43.1%), ataxia (19.6%), action tremor (15.6%), and dystonia (3.9%). Cerebellar signs were present in 37.2%. The p.Glu253Lys variant was associated with the most severe phenotype. CONCLUSIONS: KAND encompasses a continuous spectrum of motor and movement disorders that integrates developmental and neurodegenerative features. These findings inform clinical management, genetic counseling, and the design of future clinical trials.