2026 Apr 2. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2026.
ABSTRACT
CLINICAL CHARACTERISTICS: KIF1A-related neurodevelopmental disorder (KIF1A-NDD) is both a developmental and degenerative condition with a broad phenotypic spectrum commonly including developmental delay, communication difficulties, optic nerve atrophy, seizures, progressive spastic paraplegia, peripheral and autonomic neuropathy, poor weight gain, and neurobehavioral issues including autism spectrum disorder. Manifestations most commonly appear in early childhood but may be detected as early as the neonatal period. There is significant phenotypic heterogeneity.
DIAGNOSIS/TESTING: The diagnosis of KIF1A-NDD is established in a proband with suggestive findings and a heterozygous pathogenic variant or, less commonly, biallelic pathogenic variants in KIF1A identified by molecular genetic testing.
MANAGEMENT: Supportive treatment: Multidisciplinary care by specialists in education of children with developmental delay / intellectual disability; management of seizures and pain associated with peripheral neuropathy by neurologist; management by orthopedist, physical medicine and rehabilitation specialist, or occupational therapist for fine motor development; physical therapy including stretching to help avoid contractures and falls; feeding therapy to manage dysphagia; treatment by ophthalmologist to manage refractive errors; speech-language therapy to improve communication.
Surveillance: To monitor existing manifestations, the individual’s response to supportive care, and the emergence of new manifestations, regularly scheduled evaluations by treating clinicians are recommended.
GENETIC COUNSELING: KIF1A-NDD can be inherited in an autosomal dominant or, less commonly, autosomal recessive manner.
Autosomal dominant inheritance: Most individuals diagnosed with autosomal dominant KIF1A-NDD have the disorder as the result of a de novo pathogenic variant. Some individuals diagnosed with KIF1A-NDD have an affected parent. If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. If the KIF1A pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the possibility of parental gonadal mosaicism.
Autosomal recessive inheritance: If both parents are known to be heterozygous for a KIF1A pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives requires prior identification of the KIF1A pathogenic variants in the family.
Once the KIF1A pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.