Sebastian syndrome is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and inclusions in peripheral blood leukocytes (Greinacher et al., 1990).
There are several other disorders caused by mutation in the MYH9 ... Sebastian syndrome is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and inclusions in peripheral blood leukocytes (Greinacher et al., 1990). There are several other disorders caused by mutation in the MYH9 gene that share overlapping features with Sebastian syndrome. May-Hegglin anomaly (155100) shares the same triad as Sebastian syndrome, but has a different ultrastructural appearance of the leukocyte inclusions. In May-Hegglin anomaly, the inclusions are composed of clusters of ribosomes oriented along parallel microfilaments, whereas in Sebastian syndrome, the leukocyte inclusions are composed of highly dispersed filaments and few ribosomes. Fechtner syndrome (153640) has the platelet defect accompanied by nephritis, hearing loss, and eye abnormalities, mostly cataracts. Epstein syndrome (153650) has the platelet defect, deafness, and nephritis, but does not have cataract and lacks leukocyte inclusion bodies on classic staining of peripheral blood smears. The findings of nephritis, hearing loss, and occasional cataracts in Fechtner and Epstein syndromes are reminiscent of Alport syndrome (301050). Seri et al. (2003) suggested that these 4 disorders, May-Hegglin, Sebastian, Epstein, and Fechtner syndromes, are not distinct entities, but rather represent a single disorder with a continuous clinical spectrum, for which they proposed the term 'MYH9-related disease.' However, other disorders, e.g., macrothrombocytopenia and progressive sensorineural deafness (600208) and a form of nonsyndromic deafness (DFNA17; 603622), are also caused by mutation in the MYH9 gene.
Greinacher et al. (1990) described the Sebastian platelet syndrome, a variant of hereditary macrothrombocytopenia combined with the presence of neutrophil inclusions that differed from those found in patients with May-Hegglin anomaly (155100), the Chediak-Higashi syndrome (214500), or individuals ... Greinacher et al. (1990) described the Sebastian platelet syndrome, a variant of hereditary macrothrombocytopenia combined with the presence of neutrophil inclusions that differed from those found in patients with May-Hegglin anomaly (155100), the Chediak-Higashi syndrome (214500), or individuals with septicemia, and toxic Dohle bodies in polymorphonuclear leukocytes. The inclusions in polymorphonuclear leukocytes were similar to those found in patients with Fechtner syndrome (153640). Greinacher and Mueller-Eckhardt (1990) referred to the Sebastian platelet syndrome as an autosomal dominant disorder characterized by the same hematologic changes as those in the Fechtner syndrome, but without the manifestations of Alport syndrome (301050). Using immunocytochemical analysis, Seri et al. (2003) detected an irregular distribution of myosin in neutrophil cytoplasm of all 22 patients with mutations in the MYH9 gene, including 2 patients with a diagnosis of Sebastian syndrome. Large myosin aggregates appeared as Dohle-like bodies, whereas the smaller ones were not readily recognizable on Giemsa-stained peripheral blood smears. - Clinical Variability Seri et al. (2003) found sensorineural hearing loss for high tones in 9 (82%) of 11 patients initially diagnosed as having May-Hegglin anomaly or Sebastian syndrome. Three patients with May-Hegglin anomaly or Sebastian syndrome were found to have cataracts. In addition, microscopic hematuria or proteinuria was found in 4 patients with May-Hegglin anomaly and 2 with Sebastian syndrome. These clinical findings emphasized the phenotypic overlap among MYH9-related disorders.
The May-Hegglin/Fechtner Syndrome Consortium (2000) identified a heterozygous mutation in the MYH9 gene (160775.0003) in a patient with Sebastian syndrome.