title: Anticholinesterase Therapy Worsening Head Drop and Limb Weakness Due to a Novel DOK7 Mutation.
abstract: 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.
authors.affiliation: *Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO; †Prevention Genetics, Marshfield, WI; and ‡Invitae Corporation, San Francisco, CA.
authors.forename: Dominika
authors.initials: D
authors.lastname: Lozowska
authors.forename: Steven P
authors.initials: SP
authors.lastname: Ringel
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Winder
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Teerin
authors.initials: T
authors.lastname: Liewluck
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000328:Adult; D064807:Anticholinergic Syndrome / Q000209:etiology*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D004576:Electromyography; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D018908:Muscle Weakness / Q000139:chemically induced; D009154:Mutation / Q000235:genetics*; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000235:genetics
chemical_list: D002800:Cholinesterase Inhibitors; C511692:DOK7 protein, human; D009124:Muscle Proteins