Fechtner syndrome is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes, with the additional features of nephritis, hearing loss, and eye abnormalities, mostly cataracts (Peterson et ... Fechtner syndrome is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes, with the additional features of nephritis, hearing loss, and eye abnormalities, mostly cataracts (Peterson et al., 1985). There are several other disorders caused by mutation in the MYH9 gene that share overlapping features with Fechtner syndrome. May-Hegglin anomaly (155100) is characterized by the triad of thrombocytopenia, giant platelets, and Dohle body-like inclusions in peripheral blood leukocytes. 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 (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.
Peterson et al. (1985) reported a family in which 8 members of 4 generations showed nephritis, deafness, congenital cataracts, macrothrombocytopenia, and leukocyte inclusions in various combinations. The authors referred to the disorder as the 'Fechtner syndrome,' presumably from ... Peterson et al. (1985) reported a family in which 8 members of 4 generations showed nephritis, deafness, congenital cataracts, macrothrombocytopenia, and leukocyte inclusions in various combinations. The authors referred to the disorder as the 'Fechtner syndrome,' presumably from the surname of the family. The family differed from others reported, such as families with Epstein syndrome, in that their hematologic abnormalities included not only macrothrombocytopenia but also small, pale blue cytoplasmic inclusions in the neutrophils and eosinophils. Light microscopic appearance of the inclusions resembled that of toxic Dohle bodies and inclusions of May-Hegglin anomaly, but their ultrastructural appearance was unique. Deafness was high-tone sensorineural. Renal disease ranged from microscopic hematuria to end-stage renal failure necessitating dialysis and kidney transplantation. All affected adults had cataracts. Gershoni-Baruch et al. (1988) reported a second family with Fechtner syndrome; 16 members were affected. The authors noted that since the hematologic abnormalities are a consistent feature of the syndrome and seem to be present at birth, they would presumably permit prenatal diagnosis by detection of the changes in fetal blood samples. Heynen et al. (1988) described the Fechtner syndrome in a female patient who had developed multiple ecchymoses from the time she started walking at the age of 1 year, due to severe thrombocytopenia. Hearing problems developing at the age of 8 years progressed to almost complete deafness. The blood smear showed giant platelets the size of granulocytes. The patient had moderate proteinuria, but there were no abnormalities in the urinary sediment or in renal function. Heynen et al. (1988) postulated an abnormality in the cytoskeleton of megakaryocytes such that formation of the demarcation membrane system and the expulsion of platelets do not occur normally. Rocca et al. (1993) reported a 4-generation family in which 10 of 14 individuals had macrothrombocytopenia with leukocyte inclusions. Some, but not all, affected members had Alport-like symptoms, such as deafness, nephritis, and cataracts. For example, members aged less than 50 years had clinically silent ocular abnormalities, mainly lens opacities. These observations were consistent with 'reduced expression of Alport manifestations,' thus showing similarity to Sebastian syndrome. Heath et al. (2001) identified a heterozygous mutation in the MYH9 gene (E1841K; 160775.0002) in the family reported by Rocca et al. (1993).
The May-Hegglin/Fechtner Syndrome Consortium (2000) identified 2 different mutations in the MYH9 gene (160775.0005-160775.0006) in patients with Fechtner syndrome. This same group identified other mutations in the MYH9 gene in probands from families with May-Hegglin anomaly and Sebastian ... The May-Hegglin/Fechtner Syndrome Consortium (2000) identified 2 different mutations in the MYH9 gene (160775.0005-160775.0006) in patients with Fechtner syndrome. This same group identified other mutations in the MYH9 gene in probands from families with May-Hegglin anomaly and Sebastian syndrome, indicating that these disorders are allelic.