The weakness in extraocular and levator muscles is sometimes associated with more generalized myopathy of a variable degree. The myopathy may be progressive and individuals with extensive skeletal muscle weakness may have respiratory insufficiency and scoliosis. The clinical spectrum is broad and there is no consistent pattern in the degree of skeletal muscle weakness associated with ocular muscle involvement. This may be explained in part by the variety of myopathies found among patients with mutations in RYR1 such as: central core disease, multiminicore disease, congenital fiber type disproportion, centronuclear myopathy, and nemaline myopathy.
Malignant hyperthermia due to mutations in RYR1 is most commonly inherited as an autosomal dominant trait precipitated by exposure to certain volatile anesthetic agents such as halothane, isoflurane, and enflurane used in association with succinylcholine during general anesthesia. Patients may experience acidosis, muscle rigidity, rhabdomyolysis and tachycardia with arrhythmias. Myoglobinuria may lead to renal failure.
Exercise-induced heat stress rarely precipitates malignant hyperthermia.