KIF1Aassociated

KIF1A-associated refers to a group of neurodevelopmental and neurodegenerative disorders caused by variants in the KIF1A gene, which encodes a kinesin-3 family motor protein essential for anterograde transport of cargo along axons. Disruption of this transport mechanism can affect neuronal connectivity and function, leading to a broad clinical spectrum.

The umbrella term KIF1A-Associated Neurological Disorder (KAND) captures many phenotypes ranging from mild to severe. Common features include developmental delay or intellectual disability, language impairment, and motor delay. Infants may show hypotonia, with potential progression to spasticity or dystonia. Seizures occur in a subset of individuals, and autistic features or behavioral differences can be present. Visual problems such as optic atrophy or nystagmus and peripheral neuropathy may accompany the condition. Brain imaging can reveal abnormalities in some cases, though findings can also be normal.

Genetics and inheritance: Most pathogenic KIF1A variants linked to KAND are de novo and are thought to act via gain-of-function or dominant-negative effects, though inherited cases and other inheritance patterns have been reported. The phenotypic expression is highly variable, even among individuals with similar variants.

Diagnosis and management: Diagnosis relies on genetic testing, typically through exome sequencing or targeted gene panels, with clinical correlation. There is currently no cure; management is multidisciplinary and supportive, including neurology, physical and occupational therapy, vision and hearing assessment, seizure control when needed, and educational supports. Prognosis varies with the severity of neurological involvement. Ongoing research aims to better define genotype-phenotype relationships and explore targeted therapies.