Sebastian syndrome is one of the MYH9 syndromes (a group that also includes three other allelic variants with similar phenotypic expression: May-Hegglin anomaly and Fechtner and Epstein syndromes), which are characterized by a macrothrombocytopenia that is usually severe but paradoxically results in few if any symptoms. The prevalence of Sebastian syndrome is unknown. Macrothrombocytopenia is defined by the presence of giant platelets, with a diameter equal or superior to the diameter of a red cell. Sebastian syndrome, as well as May-Hegglin anomaly, is a purely hematological form of MYH9 syndrome, characterized by macrothrombocytopenia with the presence in cells of the granulocyte line of cytoplasmic inclusions similar to those observed in patients suffering from Fechtner syndrome. However, neither sensorineural deafness nor nephropathy, which define Fechtner syndrome, are present. Inclusion bodies are smaller than those observed in May-Hegglin anomaly, they are sometimes numerous and difficult to detect with usual cytological staining. Hemorrhagic manifestations occur rarely and are most often mild (thrombopenic purpura: epistaxis, profuse menstruations, ecchymoses). Sebastian syndrome is transmitted following an autosomal dominant pattern, most often as a result of mutations in the MYH9 gene. This 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.
Last update: October 2006