Abstract

The KIF1A gene encodes a protein in the kinesin-3 family which drives movement along microtubules and is important for transport of synaptic vesicles. Biallelic mutations have been identified in autosomal recessive hereditary spastic paraplegia (HSP30) and hereditary sensory and autonomic neuropathy type 1A. More recently dominant heterozygous mutations have been found in people with a more severe phenotype that includes developmental delay, spastic paraplegia, neuropathy, optic nerve hypoplasia and progressive cerebellar hypoplasia.

We report a female, now 22 years old, who has severe developmental delay, septo-optic dysplasia (requiring growth hormone and hydrocortisone replacement), sensorimotor axonal neuropathy, optic atrophy (now registered blind), non-progressive cerebellar hypoplasia, periodic limb movements and upper limb spasticity. She is extremely sensitive to gabapentin. A de novo KIF1A variant, c.814A>G, was identified. This is a novel missense variant (p.N272D) in the kinesin-motor domain.

This case shows a phenotype consistent with previously described heterozygous KIF1A mutations and we believe represents a unifying diagnosis for her neurological disabilities. No previous cases describe non-progressive cerebellar hypoplasia nor septo-optic dysplasia requiring pituitary hormone replacement. This novel mutation therefore expands the phenotype associated with KIF1A mutations. We hypothesize that her sensitivity to gabapentin may be due to the KIF1A mutation.