P.227 - The Brody disease cohort study: clarification of the phenotype

Brody disease is a rare recessive myopathy characterized by exercise-induced muscle-stiffness, caused by mutations in the ATP2A1-gene, which encodes the sarcoplasmic reticulum calcium ATPase type 1 (SERCA-1) protein. Almost fifty years after the first patient with Brody disease was reported, the clinical picture is still unclear and results of ancillary investigations remain inconclusive. This may lead to incomplete recognition and under-diagnosis of the disease. Also, little is known about the natural course of the disorder and the effects of symptomatic treatment. To improve our understanding and provide better means of recognition we studied the largest cohort of patients with Brody disease so far, consisting of all 18 previously published and 17 new patients carrying 22 novel mutations. Our study shows that the main feature of Brody disease is exercise-induced stiffness of limbs, and often also of eyelids. Onset is in childhood and there is no or only mild progression of symptoms over time. Three patients had episodes of malignant hyperthermia. The key feature of physical examination is delayed relaxation after repetitive contractions. There is no weakness or atrophy, and some patients have a remarkable athletic build. All symptomatic treatments proved ineffective. Electromyography shows no myotonia but may reveal silent contractures, CK is normal or mildly elevated and muscle biopsy shows mild myopathic changes with selective type II atrophy. Based on this large cohort, we conclude that clinicians should think of Brody disease in cases of exercise-induced muscle stiffness, especially when combined with the above-mentioned features. When physical examination shows delayed relaxation (which must be specifically looked for) and there are no myotonic discharges at electromyography, we recommend direct sequencing of the ATP2A1-gene. Finally, Brody disease patients may be at risk for malignant hyperthermia and therefore appropriate preventive measures are recommended.