Clinical Reasoning and Diagnostic Challenge in a 23-Year-Old Man With Rapidly Progressive Dysphagia and Hypophonia: Juvenile-Onset Amyotrophic Lateral Sclerosis Caused by a FUS Gene Mutation

TL;DR

A 23-year-old man with rapidly worsening swallowing and voice issues was diagnosed with a rare genetic form of motor neuron disease.

Contribution

This case highlights the importance of considering motor neuron disease in young adults with unexplained bulbar symptoms.

Findings

The patient's symptoms were caused by a pathogenic FUS gene mutation (p.Pro525Leu).

Electrodiagnostic studies showed acute to subacute denervation in tongue and trapezius muscles.

Early genetic testing and electrodiagnostic evaluation are crucial for diagnosing juvenile-onset ALS.

Abstract

Dysphagia and dysphonia of unclear etiology in young adults pose a significant diagnostic challenge, as these symptoms are more commonly attributed to benign or structural causes rather than serious neurodegenerative disease. The absence of classic neuromuscular signs such as limb weakness, hyperreflexia, or fasciculations can delay consideration of motor neuron disease, particularly when bulbar symptoms occur in isolation. We describe a previously healthy 23-year-old man who presented with rapidly progressive dysphagia and hypophonia, initially misattributed to infectious causes. Despite an extensive workup for structural, autoimmune, and infectious causes, no clear etiology was identified. Neurologic examination revealed predominantly bulbar dysfunction, and electrodiagnostic studies showed acute to subacute denervation changes in the tongue and trapezius muscles. Genetic testing confirmed juvenile-onset amyotrophic lateral sclerosis due to a pathogenic FUS gene mutation (p.Pro525Leu). This case highlights the importance of including motor neuron disease in the differential diagnosis of rapidly progressive bulbar symptoms of unknown origin. It highlights the importance of early electrodiagnostic testing and genetic evaluation in establishing a diagnosis.