# Pediatric Stroke Associated With a Rare Pathogenic PKP2 Variant: A Diagnostic Challenge

## TL;DR

A rare genetic variant in PKP2 was found in a teenager with a cerebellar stroke, highlighting the need for genetic testing in diagnosing complex pediatric stroke cases.

## Contribution

The paper presents a novel case linking a PKP2 variant to pediatric stroke and emphasizes the role of genetic testing in such scenarios.

## Key findings

- A pathogenic PKP2 variant was identified in a patient with cerebellar stroke but no structural cardiac abnormalities.
- Genetic testing informed surveillance and family screening despite no established cerebrovascular relevance of PKP2 variants.
- The case highlights diagnostic challenges when standard evaluations fail to identify stroke etiology in children.

## Abstract

Pediatric ischemic stroke is an uncommon but serious neurological condition with highly variable etiologies. Cerebellar infarctions are particularly rare in children and often present with nonspecific symptoms, contributing to delays in diagnosis. We report a case of a previously healthy 15-year-old female who presented with acute worsening headache, dizziness, vomiting, dysarthria, and left-sided neurological deficits. Neuroimaging revealed an acute non-hemorrhagic infarct in the left cerebellar hemisphere within the superior cerebellar artery territory. Given her low National Institutes of Health Stroke Scale (NIHSS) score, established infarction on MRI, and absence of a diffusion-FLAIR (fluid-attenuated inversion recovery) mismatch, mechanical thrombectomy was deferred. Standard evaluation, including echocardiography, Holter monitoring, hemoglobin electrophoresis, and thrombophilia testing, did not identify an underlying etiology. Anticoagulation was initiated due to concern for a potential cardioembolic mechanism in the setting of posterior circulation involvement, despite the absence of a documented arrhythmia. Whole-exome sequencing subsequently revealed a heterozygous pathogenic PKP2 variant associated with arrhythmogenic right ventricular dysplasia (ARVD). Cardiology evaluation, including ECG, echocardiography, and cardiac MRI, demonstrated no structural or functional abnormalities, and the patient did not meet diagnostic criteria for ARVD. She was managed with antithrombotic therapy and demonstrated gradual clinical improvement.

This case illustrates the diagnostic complexity of pediatric stroke when routine investigations fail to identify a cause and highlights the role of genetic testing in informing surveillance rather than establishing causality. Although the cerebrovascular relevance of PKP2 variants remains uncertain, their association with arrhythmogenic cardiac disease prompted ongoing cardiac follow-up and family screening. Further research is needed to clarify whether desmosomal gene variants have any independent relevance to cerebrovascular risk.