Rippling Muscle Disease in Childhood

Abstract

Rippling muscle disease is a rare autosomal dominant disorder first described in 1975. Recently, it could be classified as a caveolinopathy; in European families, mutations in the caveolin-3 gene were revealed as causing this disease. Although clinical symptoms were almost all described in adulthood, we are now reporting clinical data of seven children with rippling muscle disease owing to mutations in the caveolin-3 gene. Initial symptoms were frequent falls, inability to walk on heels, tiptoe walking with pain and a warm-up phenomenon, calf hypertrophy, and an elevated serum creatine kinase level. Percussion-/pressure-induced rapid contractions, painful muscle mounding, and rippling could be observed even in early childhood. The diagnosis can be confirmed by molecular genetic analysis. Muscle biopsy must be considered in patients without muscle weakness or mechanical hyperirritability to differentiate between rippling muscle disease and limb-girdle muscular dystrophy 1C.

Rippling muscle disease

“…4 Indeed the Arg26Gln mutation seen in our patient has been reported to be found in all of the four different phenotypic groups. [8][9][10][11][12][13][14] Our case similarly highlights this phenotypic variability with the overlapping features of local mounding and PIRC as well as distal wasting.…”

Sporadic rippling muscle disease unmasked by simvastatin

“…Immunologic testing may reveal anti‐acetylcholine receptor or anti‐striational antibodies in the former, whereas genetic analysis of caveolin‐3 may disclose missense mutations in the latter. Additionally, whereas immunohistochemistry employing caveolin‐3 and dysferlin antibodies may demonstrate a mosaic pattern of reduced sarcolemmal expression in iRMD,18 these proteins are typically absent in caveolinopathies12 although one report demonstrated preserved dysferlin immunoreactivity in a child with hRMD 17…”

Caveolinopathies: from the biology of caveolin-3 to human diseases

“…Muscle hypertony, PIRCs, PIMMs and a rippling phenomenon are represented differently in the group of the patients (Table 3). 43,45,46,[67][68][69][70][71][72][73][74] Distal myopathy (DM) There are only two reports of distal myopathy due to CAV3 mutations. Interestingly both cases are associated with the same Cav-3 aa change p.R26Q.…”

“…Cav-3 protein is 151 amino acids (aa) long and is divided in five separate domains: N-terminal (aa 1-53), scaffolding (aa [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73], transmembrane (aa 74-106), and C-terminal (aa 107-151). The N-terminal domain contains a signature sequence (aa 41-48, FED-VIAEP) that is present in all caveolins.…”