#153640
ICD+
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| FECHTNER SYNDROME; FTNS | |||||||||||||||||||||||||||
| Alternative titles; symbols | |||||||||||||||||||||||||||
| MACROTHROMBOCYTOPENIA, NEPHRITIS, DEAFNESS, AND LEUKOCYTE INCLUSIONS ALPORT SYNDROME WITH MACROTHROMBOCYTOPENIA, FORMERLY; APSM, FORMERLY | |||||||||||||||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||||||||||||||
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| Clinical Synopsis | |||||||||||||||||||||||||||
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| A number sign (#) is used with entry because Fechtner syndrome is caused by heterozygous mutation in the gene encoding nonmuscle myosin heavy chain-9 (MYH9; 160775) on chromosome 22q11. | |||||||||||||||||||||||||||
| Description | |||||||||||||||||||||||||||
| 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. | |||||||||||||||||||||||||||
| Clinical Features | |||||||||||||||||||||||||||
| 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). | |||||||||||||||||||||||||||
| Mapping | |||||||||||||||||||||||||||
| In an extended Israeli family with Fechtner syndrome plus impaired liver functions and hypercholesterolemia in some individuals, Toren et al. (1999) mapped the disease-causing gene to the long arm of chromosome 22. Six markers yielded a lod score of more than 3.00. A maximum 2-point lod score of 7.02 was obtained with the marker D22S283 at a recombination fraction of 0.0. Recombination analysis placed the disease-causing gene in a 5.5-Mb interval between markers D22S284 and D22S1167. Toren et al. (1999) stated that no collagen genes or genes comprising the basement membrane had been mapped to this region, 22q12.1-q13.2. Toren et al. (2000) mapped Epstein syndrome (153650) to the same region of chromosome 22q, suggesting that it is allelic to Fechtner syndrome. | |||||||||||||||||||||||||||
| Molecular Genetics | |||||||||||||||||||||||||||
| 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. | |||||||||||||||||||||||||||
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