Introduction: The TTN gene is a large gene that encodes for titin, which plays an important role in the sarcomere. Although mutations in the TTN gene can cause several muscle disorders including cardiomyopathies and myopathies in general, the following abstract attempts to expand the clinical spectrum of TTN mutations by including the possibility of neuropathies being associated with TTN mutations.
Methods: We report three unrelated individuals with known TTN mutations and one individuals with a TTN variant who were evaluated with clinical, laboratory, electrophysiological, or genetic testing.
Results: The mean age of onset was 40. All individuals reported neuropathic pain in their lower extremities. One had a clinical and electrophysiological results suggestive of Charcot Marie Tooth disease with bilateral foot drop and hand intrinsic weakness as well as sensory loss. One had breathing difficulties, shoulder, back and foot pain, and cardiac abnormalities with electrodiagnostic findings of a sensorimotor polyneuropathy. One had scoliosis, migraines, and back as well as foot pain who refused electrodiagnostic testing. The fourth individual had a sensorimotor polyneuropathy on exam, and a muscle biopsy suggestive of denervation and neuropathic changes.
Conclusion: The TTN gene is large with a complex structure. Given its large size, mutations in this gene may be associated with variable clinical presentations as well as neuropathies. Further investigation is indicated in expanding the clinical spectrum of TTN mutations.