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May-Hegglin anomaly is one of the MYH9 syndromes (a group that also includes three other allelic variants with similar phenotypic expression: Sebastian, Fechtner and Epstein syndrome), which are characterized by a macrothrombocytopenia that is usually severe but paradoxically results in few if any symptoms. The prevalence of May-Hegglin anomaly is unknown. Macrothrombocytopenia is defined by the presence of giant platelets, with a diameter equal or superior to the diameter of a red cell. May-Hegglin anomaly, as well as Sebastian syndrome, is a purely hematological form of MYH9 syndrome. It is characterized by the presence of cytoplasmic inclusions in cells of the granulocyte line. The cytoplasmic inclusions characterizing May-Hegglin anomaly are egg-shaped, 3 to 5 mm diameter, stain in blue in the presence of May-Grünwald-Giemsa (MGG) and are referred to as pseudo-Döhle bodies. The hemorrhagic tendency associated with this syndrome is generally mild, half of the patients being asymptomatic. However, 40% of patients have abnormal bleeding (thrombopenic purpura: epistaxis, profuse menstruations, ecchymoses). May-Hegglin thrombocytopenia is transmitted following an autosomal dominant pattern, most often as a result of point mutations in the MYH9 gene. However, twenty percent of the cases are thought to be sporadic, associated to a de novo mutation or to mosaicism. The MYH9 gene, localized to 22q12-13, encodes the nonmuscle myosin heavy chain type IIA (MYHIIA), which is expressed in some blood cells (polynuclear cells, monocytes and platelets), in the cochlea and in the kidneys. These molecular anomalies result in abnormal dimerization of the MYHIIA protein, which becomes unstable and coprecipitates with normal MYHIIA in the cytoplasm of leucocytes, thus forming cytoplasmic inclusion bodies. This abnormal dimerization also leads to a failure to properly organize the cytoskeleton in megakaryocytes, which triggers macrocytic thrombopenia. The majority of patients do not suffer from abnormal bleeding and in this case no specific treatment is required. However, platelet transfusion may be advised before surgical intervention. Life expectancy is normal. |