Objective:

To describe an atypical early-onset presentation of hereditary transthyretin amyloidosis (ATTRv) due to the Val122Ile mutation manifesting as recurrent bilateral foot drop, emphasizing the role of genetic testing in settings of atypical electrodiagnostic findings.

Background:

Foot drop has a broad differential, including focal mononeuropathies, plexopathies, radiculopathies, systemic and metabolic disorders, and hereditary neuropathies such as ATTRv. The Val122Ile variant of ATTRv typically presents in the sixth or seventh decade with isolated cardiac amyloidosis. However, neuropathic manifestations are uncommon and thus often go underrecognized, particularly in younger individuals, delaying diagnosis and early treatment options.

Design/Methods:

Case report and chart review of a patient evaluated in a neuromuscular clinic.

Results:

A 35-year-old African American woman with vitamin D deficiency, prediabetes, anxiety, depression, and migraines presented with recurrent bilateral foot drop. The initial episode followed a motor vehicle accident with bilateral tibial fractures treated with open reduction and internal fixation, with full recovery. Over subsequent years, she developed recurrent bilateral peroneal neuropathies without new trauma and progressive weakness. Nerve conduction studies (NCS) showed absent left superficial peroneal and common peroneal responses with reduced amplitudes and slowed velocities on the right. F-waves were prolonged, and sural sensory velocities were normal but relatively low for her age, suggesting early sensory involvement. Electromyography (EMG) revealed fibrillation potentials and chronic reinnervation changes. Genetic testing identified a pathogenic TTR c.424G>A (p.Val122Ile) mutation, confirming ATTRv. Cardiac evaluation showed no evidence of cardiomyopathy, and she remains under annual surveillance.

Conclusions:

The Val122Ile variant, typically linked to late-onset cardiac amyloidosis, can present decades earlier with isolated neuropathy. This case highlights the need to consider hereditary causes in recurrent focal neuropathies and to pursue genetic testing when EMG/NCS findings are atypical to enable timely diagnosis and treatment.