Historical hematology: May-Hegglin anomaly

May-Hegglin anomaly is a rare autosomal dominant platelet disorder characterized by thrombocytopenia, giant platelets, and unique leukocyte inclusion bodies. This disorder was first described by May, a German physician, in 1909, and was subsequently described by a Swiss physician, Hegglin, in 1945. The pathogenesis of the disorder had been unknown until recently, when mutations in the gene encoding for nonmuscle myosin heavy chain IIA (MYH9) were identified. Unique cytoplasmic inclusion bodies are aggregates of nonmuscle myosin heavy chain IIA, and are only present in granulocytes. It is not yet known why inclusion bodies are not present in platelets, monocytes, and lymphocytes, or how giant platelets are formed. Interestingly, MYH9 is also found to be responsible for several related disorders with macrothrombocytopenia and leukocytes inclusion, including Sebastian, Fechtner, and Epstein syndromes, which feature deafness, nephritis, and/or cataract. Current interest is centered upon the mechanisms by which a single mutation causes a variety of phenotypes.