Preliminary report for Epilepsia Open A case of West syndrome with severe global developmental delay and confirmed KIF5A gene variant

OBJECTIVE: Kinesin family member 5A (KIF5A) is a molecular motor protein responsible for intracellular transport, specifically in neurons. While abnormalities in the KIF5A gene have been reported in the onset of various neurological diseases, there are no studies demonstrating an association between this gene and West syndrome. METHODS: In the case presented here, epileptic spasms appeared at 7 months; electroencephalogram (EEG) investigation confirmed hypsarrhythmia, resulting in a diagnosis of West syndrome. The patient exhibited peculiar facies, hypotonia, failure to thrive, and severe global developmental delay. RESULTS: Cranial magnetic resonance imaging (MRI) revealed severe delayed myelination. (123)I‐iomazenil SPECT image at 7 months demonstrated decreased accumulation in bilateral areas, including the primary somatosensory and motor cortices, and the primary and association visual areas compared to an age‐matched control. Whole exome sequencing analysis demonstrated a novel de novo heterozygous missense variant in KIF5A, (NM_004984.4:c.710A>T: p. Glu237Val). SIGNIFICANCE: It was concluded that the KIF5A variant impaired the transport of GABA(A) receptors to the cell membrane surface, thus leading to an imbalance of these receptors between regions of the cerebrum and resulting in the onset of epilepsy.