Stormorken Syndrome Caused by a p.R304W Mutation: The First Italian Patient and a Review of the Literature.

Stormorken syndrome is a rare autosomal dominant disease that is characterized by a complex phenotype that includes tubular aggregate myopathy (TAM), bleeding diathesis, hyposplenism, mild hypocalcemia and additional features, such as miosis and a mild intellectual disability (dyslexia). Stormorken syndrome is caused by autosomal dominant mutations in the gene, which encodes an endoplasmic reticulum Ca sensor. Here, we describe the clinical and molecular aspects of a 21-year-old Italian female with Stormorken syndrome. The gene sequence identified a c.910C > T transition in a STIM1 allele (p.R304W). The p.R304W mutation is a common mutation that is responsible for Stormorken syndrome and is hypothesized to cause a gain of function action associated with a rise in Ca levels. A review of published mutations ( = 50) and reported Stormorken patients ( = 11) indicated a genotype-phenotype correlation with mutations in a coiled coil cytoplasmic domain associated with complete Stormorken syndrome, and other pathological variants outside this region were more often linked to an incomplete phenotype. Our study describes the first Italian patient with Stormorken syndrome, contributes to the genotype/phenotype correlation and highlights the possibility of directly investigating the p.R304W mutation in the presence of a typical phenotype. - Stormorken syndrome is a rare autosomal dominant disease.- Stormoken syndrome is caused by autosomal dominant mutations in the gene.- We present the features of a 21-year-old Italian female with Stormorken syndrome.- Our review of published mutations suggests a genotype-phenotype correlation.- The p.R304W mutation should be investigated in the presence of a typical phenotype.