[Tubular aggregate myopathy and Stormorken syndrome]

Abstract

Calcium (Ca²⁺) is an essential regulator for a large number of cellular functions in various tissues and organs, and small disturbances of Ca²⁺ homeostasis can severely compromise normal physiology. Intracellular Ca²⁺ balance is mainly controlled by the reticular Ca²⁺ sensor STIM1 and the plasma membrane Ca²⁺ channel ORAI1 through a mechanism known as store-operated Ca²⁺ entry (SOCE). Gain-of-function mutations in STIM1 or ORAI1 cause excessive extracellular Ca²⁺ influx, resulting in tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). Both disorders are spectra of the same disease and involve muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. Here we summarize the clinical and histological characteristics of both disorders, provide an overview on the genetic causes, and recapitulate the current knowledge on the pathomechanisms leading to the multi-systemic phenotype of tubular aggregate myopathy and Stormorken syndrome.