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

  1. Vorgerd M, Bolz H, Petzold T, et al. Phenotypic variability in rippling muscle disease. Neurology 1999;52:1453–1459.
  2. 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.