CHRNB1 gene mutations-related congenital myasthenic syndromes in a Chinese family / 中华神经科杂志

ABSTRACT

Objective:To analyze the clinical, neurophysiological and genetic features of CHRNB1 gene mutations-related congenital myasthenic syndromes (CMS), and to facilitate the recognition and differential diagnosis of this disorder.Methods:The clinical characteristics and laboratory features of the proband in a family with CHRNB1 gene mutations-related CMS were recorded, and the neurophysiological testing and high-throughput sequencing for the proband were performed. In addition, the response to the treatment and prognosis of the proband were reported.Results:The proband is a 16-year-old female who had bilateral eyelid ptosis at the age of 4, presented with limb weakness at the age of 12. Her father has the similar symptoms and other family members are not affected similarly. Serum creatine kinase and thyroid function were normal. Needle electromyography results demonstrated no myopathic disorders. All myasthenia gravis-related antibodies tests including anti-acetylcholine receptor antibody were negative and she failed to respond to pyridostigmine. There was a decremental response of the compound muscular action potential on 5 Hz repetitive nerve stimulation. Brain magnetic resonance imaging and chest CT were unremarkable. The proband was found a heterozygous mutation (c.865G>A (NM_000747)) in CHRNB1 gene exon 8 through high throughput sequencing. She started a 60 mg/d treatment of fluoxetine and showed beneficial response at one-year follow-up.Conclusions:The clinical presentation of CHRNB1 gene mutation-related slow-channel CMS is similar to autoimmune myasthenia gravis, and is likely to be misdiagnosed. High-throughput sequencing accelerates the diagnosis.