P.21.6 A case of familial Rippling muscle disease showing decreased of caveolin-3 in muscle biopsy suggesting an immunologic mechanism

Abstract

Rippling muscle disease (RMD), a group of disorder characterized by the muscle involuntary movement with rippling movement cross the skeletal muscle accompanied with myalgia during exercise and percussion-induced rapid muscle contraction. This disease is caused with the mutation of the caveolin-3 (CAV3) gene and PTRF gene. On the other hand, it is reported that the same immunological abnormality observed in myasthenia gravis (MG) is responsible for the onset of RMD in some sporadic cases. We have an autosomal dominant (AD) RMD family with eight patients in three-generations. Here, we describe their clinical features, muscle pathological findings, analysis of known responsible genes, and response to therapeutic agents. The proband is 56 years old female. She had an onset of sudden muscle weakness during exercise in her adolescence and soon began to feel rippling muscle phenomenon and myalgia, which lead her to be wheel chaired at her quadragenarian. In biochemical examination, mild elevation of CK is observed and gene analysis revealed no mutation in PTRF and CAV3 coding regions. Anti-AChR antibody and thymoma were not observed. In muscle biopsy, histological examination revealed decreased expression of CAV3 in muscle tissue. Administration of pyridostigmine bromide and edrophonium chloride decreased rippling muscle movement, myalgia and muscle weakness, which suggest the possibility that some immunological mechanism similar to that of MG leads to this type of RMD. We show a unique familial RMD without PTRF and CAV3 mutation. Some kinds of immunological mechanisms are considered to participate in the onset of this disease. Rippling muscle disease (RMD), a group of disorder characterized by the muscle involuntary movement with rippling movement cross the skeletal muscle accompanied with myalgia during exercise and percussion-induced rapid muscle contraction. This disease is caused with the mutation of the caveolin-3 (CAV3) gene and PTRF gene. On the other hand, it is reported that the same immunological abnormality observed in myasthenia gravis (MG) is responsible for the onset of RMD in some sporadic cases. We have an autosomal dominant (AD) RMD family with eight patients in three-generations. Here, we describe their clinical features, muscle pathological findings, analysis of known responsible genes, and response to therapeutic agents. The proband is 56 years old female. She had an onset of sudden muscle weakness during exercise in her adolescence and soon began to feel rippling muscle phenomenon and myalgia, which lead her to be wheel chaired at her quadragenarian. In biochemical examination, mild elevation of CK is observed and gene analysis revealed no mutation in PTRF and CAV3 coding regions. Anti-AChR antibody and thymoma were not observed. In muscle biopsy, histological examination revealed decreased expression of CAV3 in muscle tissue. Administration of pyridostigmine bromide and edrophonium chloride decreased rippling muscle movement, myalgia and muscle weakness, which suggest the possibility that some immunological mechanism similar to that of MG leads to this type of RMD. We show a unique familial RMD without PTRF and CAV3 mutation. Some kinds of immunological mechanisms are considered to participate in the onset of this disease.