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Anticholinesterase Therapy Worsening Head Drop and Limb Weakness Due to a Novel DOK7 Mutation

Lozowska, Dominika MD*; Ringel, Steven P. MD*; Winder, Thomas L. PhD†,‡; Liu, Jie PhD; Liewluck, Teerin MD*

Journal of Clinical Neuromuscular Disease: December 2015 - Volume 17 - Issue 2 - p 72–77
doi: 10.1097/CND.0000000000000095
Case Review

Dok-7 myasthenia is an autosomal recessive congenital myasthenic syndrome due to DOK7 mutations. Anticholinesterase therapy is ineffective and may worsen the weakness in patients with Dok-7 myasthenia or few other forms of congenital myasthenic syndromes. We describe a 31-year-old man previously diagnosed with seronegative myasthenia gravis. Repetitive stimulation of the right spinal accessory nerve showed 51% decrement. Needle electromyography revealed myopathic changes in clinically affected muscles. Muscle biopsy was normal. The patient was referred to us for worsening weakness after taking pyridostigmine. We searched for DOK7 mutations and identified compound heterozygous mutations of a common c.1124_1127dupTGCC mutation and a novel splice site mutation, c.772+2_+4delinsCCGGGCAGGCGGGCA. Discontinuation of pyridostigmine improved weakness. He further regained strength with oral albuterol therapy and decrement was reduced to 25%. Worsening of symptoms with anticholinesterase therapy in patients with “seronegative myasthenia gravis” should prompt clinicians to consider a possibility of congenital myasthenic syndromes to avoid unnecessary use of immunosuppressive therapy. Patients with Dok-7 myasthenia respond well to oral albuterol treatment.

*Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO;

Prevention Genetics, Marshfield, WI; and

Invitae Corporation, San Francisco, CA.

Reprints: Teerin Liewluck, MD, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, (e-mail:

S. P. Ringel serves as the editor of Neurology Today. T. L. Winder and J. Liu are employed by a commercial molecular diagnostic company. The remaining authors report no conflicts of interest.

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