Stormorken syndrome D69.1

Stormorken syndrome is a rare autosomal dominant genetic disorder with a complex phenotype that includes muscle fatigue, bleeding tendency associated with thrombocytopathy or thrombocytopenia, asplenia, miosis, anemia, migraine, dyslexia, ichthyosis, and short stature. Tubular aggregate myopathy (TAM) is a disease with the pathological feature of tubular aggregates in skeletal muscle. It is characterized by progressive muscle weakness and atrophy. York platelet syndrome (YPS) manifests as thrombocytopenia and calcium instability of platelets. Heterozygous mutations in Stromal Interaction Molecule 1(STIM1) have been identified as causing Stormorken syndrome (Misceo et al. 2014; Jiang Li-Jun et al.2021). Lymphoproliferation occurs frequently in this clientele. Some patients developed Coombs-positive autoimmune hemolytic anemia (AIHA) or thrombocytopenia. Autoantibodies to platelets resulted in thrombocytopenia. Normal T-cell count; defective activation of T cells via the TZR.

Misceo et al (2014) identified a heterozygous missense mutation in the STIM1 gene (R304W; 605921.0008) in 6 patients from 4 unrelated families with Stormorken syndrome (including the families primarily reported by Stormorken et al (1985)). The mutation was found in the first two families by exome sequencing. Platelets from the patients showed increased calcium levels. The mutation leads to constitutive activation of the calcium channel ORAI1 (610277), preventing further activation.

Nesin et al (2014) identified a heterozygous R304W mutation in the STIM1 gene in two unrelated patients with Stormorken syndrome. The patients' cells showed constitutive activation of the CRAC calcium channel and suppression of rapid calcium-dependent inactivation.

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