# Novel Genetic Variation in the KIF1A Gene Associated With Cerebellar Vermis Hypoplasia: A Case Report

## TL;DR

A two-year-old girl with developmental delays and cerebellar vermis hypoplasia was found to have a new KIF1A gene mutation, highlighting the need for more research on this rare disorder.

## Contribution

A novel de novo KIF1A gene mutation (c.464G>C, p.R155P) is reported in a patient with cerebellar vermis hypoplasia and neurological symptoms.

## Key findings

- The patient had a de novo heterozygous missense mutation in the KIF1A gene at 2q37.3.
- MRI findings and symptoms suggest a genetic basis for cerebellar vermis hypoplasia.
- The mutation is classified as a variant of uncertain significance but correlates with severe symptoms.

## Abstract

KIF1A-associated neuronal disorder (KAND) is a spectrum of disease caused by a genetic mutation in the KIF1A gene. Genetic variants in this gene have been associated with cerebellar vermis hypoplasia, as well as mild to severe symptoms, including ataxia, motor and global developmental delay, and intention tremors. Given the limited number of reported cases, ample research is necessary to effectively manage this condition.

A two-year-old girl presents with global developmental, motor, and speech delay, as well as jerky movements, possible athetosis, hand tremors, ataxia, vertical nystagmus, and muscle spasticity in lower limbs. She was referred to the clinic by her neurologist due to abnormal findings in her MRI, which showed cerebellar vermis hypoplasia. These results, together with her symptoms, suggested a genetic basis, for which a chromosomal microarray (CMA) was indicated. Results for the CMA showed two regions of homozygosity, prompting a whole-exome sequencing to be performed. This test revealed an autosomal dominant heterozygous missense mutation known as c.464G>C (p.R155P). Because there was no significant family history correlating with this disease, it appears that the mutation appeared de novo. The gene affected by this mutation is the KIF1A gene, which is located in 2q37.3. The KIF1A gene is responsible for encoding the kinesin-like protein KIF1A. This protein is responsible for microtubule motor function, as well as adenosine triphosphate (ATP) binding. Even though the mutation found in this patient was classified as a variant of uncertain significance, her severe symptoms suggest a pathological correlation. Her prognosis is reserved as there is no targeted treatment available.

Due to the low incidence of this disease and the possibility of neurodegeneration in patients, more research is encouraged to develop effective disease management.