Fluctuating Ophthalmoplegia Presenting as a Treatable Manifestation of Myotonia Congenita (P02.263)

Abstract

Objective: To present a case of myotonia congenita presenting with fluctuating ophthalmoplegia that responded to treatment with mexiletine. Background Myotonia congenita is a disorder of prolonged muscle stiffness and myotonia following voluntary muscle contraction due to a mutation in the CLCN1 gene encoding a skeletal muscle voltage-gated chloride channel. The disease involves striated muscles, and extraocular muscle involvement has been demonstrated in reports. Such patients may manifest with lid lag, blepharospasm, and impaired saccades, but there have been no reported attempts to treat the disabling extraocular manifestations with medical therapy. Design/Methods: Case report. Outcome measures were based on patient9s report of symptom control as well as serial neurological examinations. Results: A 68 year old woman presented with 2 years of intermittent, fluctuating, binocular oblique diplopia and occasional stiffness in her arms and legs. Her examination was notable initially for an intermittent right hypertropia, esophoria, and ptosis, and later for a transient right exophoria and mild proximal weakness. Unexpectedly, her EMG demonstrated profound myotonia. Genetic testing revealed a mutation in the CLCN1 gene as is seen in myotonia congenita; genetic testing was negative for myotonic dystrophy types 1 and 2, and there was no evidence of myasthenia gravis on single fiber EMG or acetylcholine receptor antibody testing. She failed an initial trial of pyridostigmine, but her symptoms responded to mexiletine. Conclusions: This is the first reported case of a patient with genetically confirmed CLCN1 gene mutation presenting with fluctuating diplopia as an initial symptom of myotonia congenita. Her symptoms likely reflected involvement of extraocular muscles and responded to mexiletine, suggesting an underlying mechanism of myotonia involving extraocular muscles. Myotonia congenita should be considered in the differential diagnosis of fluctuating ophthalmoplegia, particularly in patients with electrophysiological myotonia. The symptoms may be underrecognized, can mimic other disease processes, and are potentially responsive to medical treatment with mexiletine. Disclosure: Dr. Odrzywolski has nothing to disclose. Dr. Johnson has nothing to disclose. Dr. Twydell has received personal compensation for activities with Allergen, Inc. as a speaker. Dr. Twydell has received personal compensation in an editorial capacity for UpToDate.