KIF5C-Related Neurodevelopmental Disorder: Three New Cases and Additional Neuroradiologic Insights
Davide Politano1,2, Simone Gana3, Simona Orcesi1,2
1Department of Brain and Behavioral Sciences, University of Pavia, Italy.
Neurology. Genetics
|May 18, 2026
Summary
Pathogenic KIF5C variants cause neurodevelopmental disorders. This study reveals a wider spectrum of clinical, genetic, and neuroimaging findings, including cases without classic cortical malformations, expanding diagnostic understanding.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- KIF5C encodes a neuronal kinesin motor protein.
- Pathogenic variants in KIF5C cause a rare neurodevelopmental disorder.
- The disorder is characterized by global developmental delay, absent speech, motor disability, epilepsy, and behavioral issues.
Purpose of the Study:
- To evaluate individuals with KIF5C variants.
- To compare findings with previously reported cases.
- To broaden the understanding of the KIF5C-related disorder spectrum.
Main Methods:
- Clinical, neuroimaging, and genetic assessments of three individuals.
- Literature review via PubMed search for "KIF5C" (March 2, 2025).
- Inclusion of English-language articles with detailed clinical descriptions.
Main Results:
- Two participants had the recurrent c.709G > A, p.(Glu237Lys) variant; one had a novel c.606C > G, p.(Ser202Arg) variant.
- All individuals presented with severe neurodevelopmental impairment.
- Neuroimaging showed complex brain malformations, including anterior pachygyria, white matter and cerebellar abnormalities; one case lacked overt cortical malformations.
Conclusions:
- KIF5C-related disorder has a broader clinical, genetic, and neuroimaging spectrum than previously recognized.
- The disorder can occur without classic cortical malformations.
- White matter and cerebellar involvement suggest disruption of multiple neurodevelopmental processes, highlighting the need for expanded phenotype recognition for diagnosis, understanding, and management.
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