About RYR-1-Related Diseases
Overview: RYR-1-related diseases are inherited forms of myopathy resulting in a wide range of symptoms, including muscle weakness, a potentially fatal reaction to general anesthesia (malignant hyperthermia), and rhabdomyolysis. Patients are born with RYR-1-related diseases, inheriting a defective mutation from one or both parents, or a spontaneous mutation (de novo). Mutations or changes in the RYR1 gene are the most common cause of congenital muscle myopathy. The RyR1 receptor is a channel in muscle cells that regulate the flow of calcium, a critical component of muscle contraction. A reduced number and/or abnormal RyR1 channels lead to dysfunctional muscle contraction. There is a wide range of symptoms of RYR-1-related diseases but are typically either non-progressive or very slowly progressive.
Symptoms: Common symptoms include weakness of the eye muscles and generalized muscle weakness, typically affecting the muscles closest to the torso of the body. Some individuals experience muscle cramping and pain, difficulties exercising, and intolerance to heat. There are typically no heart problems and intelligence is not affected.
Breathing Problems: Breathing problems associated with RYR-1-related diseases can range from non-existent to severe and are due to weakness in the muscles of the chest wall. Mild breathing problems can include sleep apnea (stop breathing while asleep), requiring breathing support during sleep. Severe breathing problems require continuous support.
Malignant Hyperthermia: Changes in the RYR1 gene have also been associated with malignant hyperthermia, a severe and potentially fatal reaction to certain types of anesthesia (drugs given by doctors for medical/surgical procedures). Anyone with an RYR1 genetic abnormality should take "malignant hyperthermia precautions" if anesthesia is required for a medical/surgical procedure. Please click here for a guide for patients at risk for malignant hyperthermia.
Diagnosis: RYR-1-related diseases are diagnosed with genetic testing. In addition, a muscle biopsy can be performed, which allows doctors to examine the muscle under the microscope and look for changes at a cellular level that may be associated with RYR-1-related diseases. MRI also allows the doctors to look for characteristic changes in the muscle at a structural level.
How does someone get RYR-1-related diseases? RYR-1-related diseases are due to a change or mutation in the RYR1 gene. This mutation in the RYR1 gene is usually inherited from one or both parents, who may or may not be affected by the disease. There are two types of inheritance patterns for changes in this gene: autosomal dominant and autosomal recessive. "Recessive" means that both "copies" of the gene must have mutations for the patient to be affected; if only one copy is defective, the patient will be a carrier and not be affected clinically (signs & symptoms). "Dominant" means that even if only one copy of the gene is defective, the patient will be affected by the disease.
Treatment: At this time, no cure exists for RYR-1-related diseases. The goal of this Foundation is to help find one.
To get a more in-depth overview written by Dr. Michael Goldberg, MD, MPH for the National Organization for Rare Disorders (NORD), please click HERE or on the image below: