Rippling Muscle Disease

Rippling muscle disease (RMD) is a rare neuromuscular disorder where the muscles are susceptible to movement or pressure. This disorder belongs to a group of conditions called caveolinopathy, including limb-girdle muscular dystrophy 1C, isolated hyperCKemia, CAV3-related distal myopathy, and hypertrophic cardiomyopathy.

Rippling muscle disease is a genetic disorder caused by mutations in the CAV3 gene and PTRF/CAVIN1 genes, which encode for a  protein called caveolin-3 found in the membrane surrounding muscle cells. Inheritance of rippling muscle disease primarily occurs in an autosomal dominant pattern, whereby only one copy of the defective gene is necessary for developing the condition. A few cases have also been associated with autosomal recessive inheritance, meaning two copies of the defective gene are required to develop the condition. The few instances associated with autosomal recessive inheritance appear more severe, sometimes with cardiac involvement. There have also been reports of sporadic cases of rippling muscle disease associated with myasthenia gravis, an autoimmune disorder where the immune system attacks the neuromuscular junction in skeletal muscle. More recently, Cavin-4 autoantibodies have been found to play a pathogenic role in rippling muscle disease associated with thymomas, a rare type of tumor arising from the thymus gland's epithelial cells.

Signs and symptoms of rippling muscle disease are related to increased muscle irritability and can include muscle stiffness, muscle hypertrophy, and rippling muscle induced by stretching or percussion. The age of onset of the symptoms varies widely, though they usually begin in late childhood or adolescence. 

In most people with rippling muscle disease, stretching the muscle causes involuntary rippling described akin to worm or wave-like muscle contractions. A bump or sudden impact on the muscle can cause it to bunch up, a phenomenon known as percussion-induced muscle mounding. Tapping the muscle can also lead to repetitive tensing, known as percussion-induced rapid contraction. The rapid contractions can continue for up to a minute and may become painful. Additionally, some individuals experience fatigue, cramps, and muscle stiffness, especially after strenuous physical activity or exposure to cold temperatures. Finally, there may also be hypertrophy or overgrowth of the thigh and leg muscles leading to an unusual gait. 

Rippling muscle disease is usually suspected based on the medical history, physical exam, and compatible family history. People with rippling muscle disease often present high levels of creatine kinase (CK) on blood tests, which may aid in the diagnosis. Additional testing may include electromyography, which measures the electrical activity of muscles, and a muscle biopsy. 

Treatment of rippling muscle disease is usually unnecessary since most individuals present with mild or asymptomatic symptoms. In cases where rippling muscle disease is associated with myasthenia gravis or thymoma, treatment may involve immunosuppressive medications like corticosteroids and surgical removal of the thymus, respectively. In individuals with severe muscle stiffness and painful cramps, treatment with dantrolene or benzodiazepines may help decrease muscle irritability.  

Rippling muscle disease is a rare neuromuscular disorder characterized by wave-like muscle contractions, muscle stiffness, and muscle hypertrophy, usually with elevated serum creatine kinase levels in the blood. Mutations in the CAV3 gene typically cause it and are generally inherited in an autosomal dominant fashion. Diagnosis is suspected based on a clinical history and physical exam, while genetic testing can obtain confirmation. Treatment depends on the severity of the condition and may include dantrolene or benzodiazepines to decrease muscle irritability.