Morvan’s syndrome and myasthenia gravis related to familial Mediterranean fever gene mutations

Junpei Koge, Shintaro Hayashi, Hiroyuki Murai, Jun Yokoyama, Yuri Mizuno, Taira Uehara, Naoyasu Ueda, Osamu Watanabe, Hiroshi Takashima, Jun-ichi Kira

We present the first case of Morvan's syndrome (MoS) and myasthenia gravis (MG) related to familial Mediterranean fever (FMF) gene mutations. A 40-year-old woman with a 1-year history of bilateral ptosis and limb muscle weakness presented to our hospital. She also had memory impairment, insomnia, hyperhidrosis, and muscle twitches. Electromyography confirmed widespread myokymia, and there was evidence of temporal region dysfunction on electroencephalography. Anti-voltage-gated potassium channel complex antibodies and anti-acetylcholine receptor antibodies were both positive. Edrophonium administration was effective for bilateral ptosis and muscle weakness. She and her family experienced self-limiting febrile attacks with arthralgia, which led us to suspect FMF. Genetic analyses revealed compound heterozygous mutations in exon 2 of the MEFV gene (L110P/E148Q). From these findings, a diagnosis of MoS and MG complicated with MEFV gene mutations was made. Intravenous high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin resulted in only transient, limited improvement, and frequent relapses, especially in the myasthenic symptoms. Interleukin (IL)-6, IL-1β, and tumor necrosis factor-α were markedly elevated in the serum, which was considered to be derived from the MEFV mutations and responsible for the resistance to immunotherapy. The present case illustrates a possible link between auto-inflammation and auto-antibody-mediated neurological diseases.