Epstein syndrome is an autosomal dominant disorder characterized by thrombocytopenia, giant platelets, nephritis, and deafness (Epstein et al., 1972).
There are several other disorders caused by mutation in the MYH9 gene that share overlapping features with ... Epstein syndrome is an autosomal dominant disorder characterized by thrombocytopenia, giant platelets, nephritis, and deafness (Epstein et al., 1972). There are several other disorders caused by mutation in the MYH9 gene that share overlapping features with Epstein syndrome. May-Hegglin anomaly (155100) is characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes. These leukocyte inclusions are not found on classic staining of peripheral blood in Epstein syndrome. Fechtner syndrome (153640) has the platelet defect accompanied by nephritis, hearing loss, and eye abnormalities, mostly cataracts. The findings of nephritis, hearing loss, and occasional cataracts in Fechtner and Epstein syndromes are reminiscent of Alport syndrome (see 301050). Sebastian syndrome (605249) is similar to May-Hegglin anomaly, but has a different ultrastructural appearance of the leukocyte inclusions. 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.
Epstein et al. (1972) described 2 unrelated families, each with 2 members with macrothrombocytopathia, nephritis, and deafness. In 1 family, a third member, a young child, had the platelet disorder and a mild hearing loss. Except for the ... Epstein et al. (1972) described 2 unrelated families, each with 2 members with macrothrombocytopathia, nephritis, and deafness. In 1 family, a third member, a young child, had the platelet disorder and a mild hearing loss. Except for the greater severity in females, the renal disease was indistinguishable from that of X-linked Alport syndrome (301050). Likewise, the high frequency sensorineural hearing loss was similar to that of the Alport syndrome. Thrombocytopenia was present with giant platelets showing abnormal ultrastructure and defective adherence to glass, and the bleeding time was prolonged. Aggregation of platelets in response to collagen and epinephrine and release of phospholipids were all impaired, and the release of nucleotide after exposure to collagen was abnormally low. Parsa et al. (1976) reported another kindred with the triad of hereditary nephritis, deafness, and thrombocytopenia with giant platelets. Electron microscopic studies of megakaryocytes led the authors to suggest that the giant platelets may result from a degenerative process in megakaryocytes leading to nuclear regression and cytoplasmic fragmentation, rather than from the normal blebbing process. Giant platelets also occur in the Fechtner syndrome and in association with the May-Hegglin anomaly. 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 5 patients with a diagnosis of Epstein 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 Utsch et al. (2006) reported a newborn girl with Epstein syndrome and a heterozygous mutation in the MYH9 gene (160775.0012). Although she did not show deafness or nephritis, she had macrothrombocytopenia and impaired platelet aggregation response to ADP and epinephrine. Bone marrow aspirate showed enhanced megakaryocytopoiesis with predominance of immature and dysplastic megakaryocytes. Erythropoiesis and granulocytopoiesis were normal. In addition, she had classic exstrophy of the bladder (600057). Prenatal ultrasound studies showed protrusion of the abdominal wall and a single umbilical artery. After birth, she was noted to have diastasis of the symphysis, epispadic open urethral groove, bifid clitoris and labia minora, an open laying bladder plate, and duplication of the vagina. The authors noted the young age of the patient, and suggested that she may develop deafness and/or nephritis in the future. Utsch et al. (2006) suggested that although MYH9 mutations had not previously been associated with urogenital malformations, the mutation may have played a role in the bladder exstrophy in this patient.
Heath et al. (2001) found that the original family reported by Epstein et al. (1972) had a missense mutation in the gene that encodes nonmuscle myosin heavy chain IIA (MYH9; 160775.0006), which is also the site of mutations ... Heath et al. (2001) found that the original family reported by Epstein et al. (1972) had a missense mutation in the gene that encodes nonmuscle myosin heavy chain IIA (MYH9; 160775.0006), which is also the site of mutations causing other forms of autosomal dominant macrothrombocytopenia: May-Hegglin anomaly, Fechtner syndrome, and Sebastian syndrome.