[ MIM 601 003, 108 730]

Estimated prevalence 1.106  but it could be underdiagnosed. Autosomal recessive transmission of mutations of the ATP2A1 (16p12) gene coding for a Ca-dependent ATPase of the sarcoplasmic reticulum (SERCA1) within the type II skeletal muscle fibers (short effort). This mutation results in a slowing down of Ca ++ entry in the sarcoplasmic reticulum after a muscle contraction and thus increased cytoplasmic Ca++ levels.

The first signs appear during the first decade. They are most often painless muscle tightness or cramps, after an important exercise or fast movements (impossibility to run). This stiffness disappears after a few seconds of rest. There is no myotonia if an EMG is performed during an episode of muscle stiffness, but an absence of electrical activity (silent contracture). All the muscles can be affected (mostly in the upper and lower limbs and in of the eyelids) and the cold makes the episodes of stiffness more frequent.

Risk of clinical malignant hyperthermia: two cases mimicking MH crisis and a case of exercise-induced rhabdomyolysis have been reported but without any mutation of the RYR1 gene. The contracture tests are positive due to the increased intracytoplasmic Ca++ level but without any hypermetabolism.

CPK levels: normal or slightly increased.

Biopsy: mild atrophy of the type II muscle fibers

Treatment: dantrolene and verapamil orally can be efficacious

Anesthetic implications:

the positivity of the contractures tests (halothane, caffeine) as performed for malignant hyperthermia is probably an artifact caused by delayed relaxation of the typeII muscle fibers. But due to the possible risk of anesthesia-induced rhabdomyolysis (AIR), it is wise to avoid halogenated volatile anesthetics as well as succinylcholine. Hypothermia should be prevented.

References : 

-         Benca J, Hogan K. 
Malignant hyperthermia, coexisting disorders, and enzymopathies: risks and management options. 
Anesth Analg 2009; 109: 1049-53.

-        Voermans NC, Laan AE, Oosterhof A, van Kuppevelt TH et al. 
Brody syndrome: a clinically heterogenous entity distinct from Brody disease. A review of literature and a cross-sectional clinical study in 17 patients. 
Neuromuscul Disord 2012; 22: 944-54 

-        Molenaar JP, Verhoeven JI, Rodenburg RJ, Kamsteeg EJ, Erasmus CE et al. 
Clinical, morphological and genetical characterization of Brody disease: an international study of 40 patients.
Brain 2020 ; 143 : 452-66

Updated: June 2020