Phenotypic variability in rippling muscle disease

Objective: To characterize the phenotype of hereditary rippling muscle dise ase (RMD) and to report the results of genetic linkage studies. Background: RMD is a rare autosomal-dominant inherited muscle disorder. Individuals co mplain of muscle stiffness, exercise-induced muscle pain, and cramp-like se nsations. The characteristic feature of RMD is increased mechanical muscle irritability, which is electrically silent in electromyographic examination s. Methods: Forty-six individuals from two unrelated German kindreds with R MD were examined. Linkage analysis to the RMD locus on chromosome 1q41-q43 was performed. Results: In kindred A, 15 individuals from four generations, and in kindred B, four individuals from three generations had clinical fea tures of RMD. The most consistent clinical findings were percussion-induced rapid muscle contractions (PIRCs) and muscle mounding, which were present in all 19 affected individuals. Only 12 individuals exhibited muscle rippli ng, indicating that rippling is not always present in RMD. Twelve of 19 ind ividuals had muscle-related complaints, primarily exertional cramps and sti ffness. The mean age at the onset of complaints was 22 years (range, 5 to 5 4 years). Seven of 19 individuals showed only mechanical-induced muscle irr itability but did not have muscular symptoms. Genetic analysis excluded lin kage to the RMD locus on chromosome 1q4 in both kindreds. Conclusions: The phenotype of RMD is variable but generalized PIRCs are the most obvious and reliable clinical feature of RMD. Diagnostic criteria of RMD should includ e generalized PIRCs in addition to muscle mounding, rippling, and creatine kinase elevation.