Objective: To report a rare presentation of a homozygous PRRT2 frameshift mutation manifesting as infantile-onset seizures followed by childhood episodic gait imbalance.

Background: PRRT2 mutations are commonly associated with self-limited infantile epilepsy and paroxysmal kinesigenic dyskinesia. Episodic ataxia is rarely described and remains an underrecognized manifestation.

Method: Clinical evaluation, neuroimaging, electroencephalography, metabolic testing, and next-generation sequencing were performed in a child presenting with early-onset seizures and episodic gait imbalance.

Results: A 10-year-old boy presented with clusters of afebrile seizures beginning at 4 months of age, controlled with antiseizure medication. From 18 months onward, he developed recurrent brief episodes of gait imbalance occurring several times per year without loss of consciousness. Neurological examination between episodes was normal. Brain MRI, EEG, and metabolic investigations were unremarkable. Whole-exome sequencing identified a homozygous PRRT2 frameshift variant (c.649dup; p.Arg217Profs*8). Segregation analysis demonstrated heterozygosity in both parents. Treatment with carbamazepine resulted in complete resolution of seizures and gait imbalance during follow-up.

Conclusion: This case expands the phenotypic spectrum of PRRT2-associated disorders by demonstrating episodic gait ataxia following infantile-onset epilepsy in the setting of a homozygous frameshift mutation. Recognition of this phenotype is important as symptoms may respond well to sodium channel–blocking therapy.

Figure 1. Pedigree chart

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MDS Abstracts - https://www.mdsabstracts.org/abstract/homozygous-prrt2-frameshift-mutation-presenting-with-infantile-onset-seizures-and-childhood-episodic-ataxia/