May-Hegglin anomaly is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes. About 25 to 50% of affected individuals have mild to moderate episodic bleeding (summary by ... May-Hegglin anomaly is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes. About 25 to 50% of affected individuals have mild to moderate episodic bleeding (summary by Kelley et al., 2000). There are several other disorders caused by mutation in the MYH9 gene that share overlapping features with May-Hegglin anomaly. 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). Sebastian syndrome (605249) is the most similar to May-Hegglin anomaly, but has a different ultrastructural appearance of the leukocyte inclusions. In MHA, 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. Seri et al. (2003) suggested that these 4 disorders, May-Hegglin, Fechtner, Sebastian, and Epstein 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.'
May (1909) described inclusion bodies in granulocytes from the peripheral blood of an asymptomatic 24-year-old woman. Hegglin (1945) observed the triad of thrombocytopenia, giant platelets, and inclusion bodies in the leukocytes in 2 generations of a family. The ... May (1909) described inclusion bodies in granulocytes from the peripheral blood of an asymptomatic 24-year-old woman. Hegglin (1945) observed the triad of thrombocytopenia, giant platelets, and inclusion bodies in the leukocytes in 2 generations of a family. The leukocyte inclusions consisted of cytoplasmic RNA-containing inclusions, so-called Dohle bodies, which can also be seen transiently during acute infections. Oski et al. (1962) observed the anomaly in a mother and her 2 children. Of 24 reported cases, 9 had thrombocytopenia. On the basis of electron microscopic studies, Jenis et al. (1971) suggested that the inclusions represented paracrystalline arrays of depolymerized ribosomes. Jenis et al. (1971) suggested a hypothetical model for the development of the May-Hegglin inclusion based on ultrastructural studies of marrow precursors containing the inclusions. They suggested that the filaments represent completely unfolded, i.e., depolymerized, ribosomes. Similar basophilic inclusions occurred in the Fechtner syndrome. Fujita et al. (1990) described the May-Hegglin anomaly in a 39-year-old male and his son and daughter. All 3 also had spastic paraplegia, which began in the offspring at about age 12 and in the father at about age 20. Renal function was normal. In a patient with end-stage renal failure being prepared for renal transplant and in his healthy brother, Nel et al. (1992) found the May-Hegglin anomaly. They concluded that there was no relation to the renal failure. Almost all neutrophils contained at least one inclusion body. These bodies were larger than toxic Dohle bodies found in septicemia, stained better, and were not accompanied by toxic granulation in the cytoplasm. Most of the inclusions were spindle shaped and occurred in any location in the cell cytoplasm as compared with the smaller, more irregular or rounded Dohle bodies, which tended to have a peripheral location in the cell. On electron microscopy, the bodies were shown to have parallel filaments oriented in the long axis of the inclusion. Greinacher et al. (1992) described 2 families with May-Hegglin anomaly, one with 4 and the other with 3 affected persons. Platelet counts were markedly reduced and were correctly determined only in the counting chamber. Bleeding time and platelet aggregation were normal, but platelet nucleotide concentrations (ATP and ADP) were elevated. Giant platelets and spindle-shaped inclusion bodies were found in the granulocytes, which functioned normally. Both families were ascertained through a child who was found to have thrombocytopenia during acute infection. Misdiagnosis in such cases can lead to mismanagement, including the use of dangerous therapy. - 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 findings emphasized the phenotypic overlap among MYH9-related disorders.
The May-Hegglin/Fechtner Syndrome Consortium (2000) identified 6 MYH9 mutations in 7 unrelated probands with one or another of the 3 autosomal dominant giant platelet disorders: May-Hegglin anomaly, Fechtner syndrome, and Sebastian syndrome. Kelley et al. (2000) likewise identified ... The May-Hegglin/Fechtner Syndrome Consortium (2000) identified 6 MYH9 mutations in 7 unrelated probands with one or another of the 3 autosomal dominant giant platelet disorders: May-Hegglin anomaly, Fechtner syndrome, and Sebastian syndrome. Kelley et al. (2000) likewise identified mutations in the MYH9 gene in patients with May-Hegglin anomaly. In 5 of 10 families, they found an E1841K mutation (160775.0002) that the May-Hegglin/Fechtner Syndrome Consortium (2000) found in 2 families. In 4 of 10 families, they found an R1922X mutation (160775.0001) that the May-Hegglin/Fechtner Syndrome Consortium (2000) found in 1 family. In the remaining family of the 10 studied, they found a T1155I mutation (160775.0007).