June 22, 2020 e-Pearl of the Week: Primary Rippling Muscle Disease Associated with CAV3 Mutation
Primary Rippling Muscle Disease Associated with CAV3 Mutation
Rippling muscle disease (RMD)—a caveolinopathy—is characterized by wave-like contractions and muscle-mounding due to spontaneous or mechanical (percussive) stimulation.1,2 RMD results from CAV3 mutation on chromosome 3p25—predominantly in an autosomal dominant pattern, and is occasionally autosomal recessive—causing dysfunction of Caveolin—a T-tubule protein).2 RMD manifests in childhood and adolescence, but rarely in adulthood. While CAV3 mutation exhibits variable expressivity, RMD has propensity for quadriceps and biceps brachii.2 RMD has a generally benign clinical course that typically presents with fatigue, difficulty in plantar-flexed ambulation, positive Gower’s sign, cramping, myalgia, and stiffness, especially with exercise. Diagnostic tests demonstrate serum CK 3-25X normal, needle-silence on EMG, and decreased Caveolin on immunohistochemistry (confirmatory).1 Physical therapy is the mainstay of treatment, while dantrolene or benzodiazepines are reserved for refractory cases.1
References
- Vorgerd M, Bolz H, Petzold T, et al. Phenotypic variability in rippling muscle disease. Neurology 1999;52:1453–1459.
- Betz RC, Schoser BG, Kasper D, et al. Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease. Nat Genet 2001;28:218–219.
Submitted by Ahmed Naffi, MD,, PA, Research Associate Sugar Land Neurology & Sleep (Sugar Land, Texas), and M. Faisal Khan, MD, DABSM, DABPN, Consultant Neurologist, Sugar Land Neurology & Sleep (Sugar Land, Texas)
Ahmed Naffi & Dr. Khan report no disclosures.