Objective:

To analyze the role of KIF1A gene expression in the setting of FLAIR signal abnormalities and related clinical manifestations, with incomplete penetrance of the variant.

Background:

KIF1A is a gene that codes for a neuron-specific kinesin that is responsible for anterograde transport of cell precursors along microtubules. KIF1A gene mutations can lead to a spectrum of neurological disorders known as KIF1A-associated Neurological Diseases (KAND). Symptoms can range from mild to severe, including hypotonia, peripheral neuropathy, spasticity, epilepsy, developmental delay and optic atrophy. KAND is ultra-rare, with approximately 500 diagnosed cases worldwide. In this case, we highlight a rare phenotype of adult-onset progressive weakness and sensory loss.

Design/Methods:

NA

Results:

We present a case study of a 35-year-old African American female with a history of traumatic optic nerve atrophy who presented with intermittent, recurring left-sided paresthesia and hemiparesis. Initial imaging of her neuroaxis, nerve conduction studies and EMG were unrevealing. Four years later, she developed FLAIR abnormalities in the bilateral cerebral hemispheres without contrast enhancement. She was diagnosed with atypical acute disseminated encephalomyelitis (ADEM) and started on IVIG and a steroid taper, resulting in improvement in muscle strength. Given the concern for potential MELAS (Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Symptoms) versus POLG-related disorder (inherited mitochondrial disorder), whole exome sequencing (GeneDx XomeDx Plus) was obtained, which was positive for the KIFIA heterozygous gene mutation [c. 4697 A>G p.(1566G)]. The patient’s asymptomatic mother also tested positive for the same mutation, suggesting incomplete penetrance of the variant, with epigenetic and environmental factors potentially playing a role in disease manifestation.

Conclusions:

Our case demonstrates that KAND can have phenotypic similarities to “recurrent ADEM.” It also suggests that KAND does not emerge exclusively in the pediatric population. Ours is the only case of the KIFIA heterozygous mutation [c. 4697 A>G p. (1566G)] that is identified as potentially pathologic.