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Phenotypic variability in rippling muscle disease
1Department of Neurology, Ruhr-University, Bochum, Germany. matthias.vorgerd@ruhr-uni-bochum.de
Objective:
To characterize the phenotype of hereditary rippling muscle disease (RMD) and to report the results of genetic linkage studies.
Background:
RMD is a rare autosomal-dominant inherited muscle disorder. Individuals complain of muscle stiffness, exercise-induced muscle pain, and cramp-like sensations. The characteristic feature of RMD is increased mechanical muscle irritability, which is electrically silent in electromyographic examinations.
Methods:
Forty-six individuals from two unrelated German kindreds with RMD 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 features 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 rippling, indicating that rippling is not always present in RMD. Twelve of 19 individuals had muscle-related complaints, primarily exertional cramps and stiffness. The mean age at the onset of complaints was 22 years (range, 5 to 54 years). Seven of 19 individuals showed only mechanical-induced muscle irritability but did not have muscular symptoms. Genetic analysis excluded linkage 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 include generalized PIRCs in addition to muscle mounding, rippling, and creatine kinase elevation.
Insights
Hereditary rippling muscle disease (RMD) is characterized by variable symptoms, but generalized percussion-induced rapid muscle contractions (PIRCs) are the most reliable clinical feature. Genetic analysis excluded linkage to the previously identified RMD locus.
Area of Science:
- Neurology
- Genetics
- Rare Diseases
Background:
- Hereditary rippling muscle disease (RMD) is a rare, autosomal-dominant neuromuscular disorder.
- Patients typically experience muscle stiffness, exercise-induced pain, and cramping, with characteristic electrically silent mechanical muscle irritability.
Observation:
- This study examined 46 individuals from two German kindreds with suspected RMD.
- Clinical evaluation focused on characterizing the phenotype and performing genetic linkage analysis.
Findings:
- Percussion-induced rapid muscle contractions (PIRCs) and muscle mounding were consistently observed in all 19 affected individuals.
- Muscle rippling was present in only 12 individuals, indicating variable expressivity.
- Genetic linkage analysis excluded the previously identified RMD locus on chromosome 1q4 in both kindreds.
Implications:
- Generalized PIRCs are the most reliable clinical diagnostic feature of RMD.
- Diagnostic criteria for RMD should incorporate PIRCs, muscle mounding, rippling, and creatine kinase levels.
- Further genetic studies are needed to identify the causative gene for RMD.