Fechtner syndrome

Fechtner syndrome, like the May-Hegglin anomaly (155100) and the Sebastian syndrome (605249) (2 giant-platelet disorders) are caused by allelic mutations in the gene encoding nonmuscle myosin heavy chain-9 (MYH9; 160775) on chromosome 22q.

The name of the syndrome is derived from teh surname of a family in which 8 members of 4 generations developed nephritis, deafness, congenital cataracts, macrothrombocytopenia, and leukocyte inclusions in various combinations. 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. 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.

A second family was reported on by Gershoni-Baruch et al. in 1988 in which 16 members were affected.

Diagnosis
The blood smear can show giant platelets which are the size of granulocytes. By light microscopy, there is the appearance of the inclusions that resemble that of toxic Dohle bodies and inclusions of May-Hegglin anomaly, but their ultrastructural appearance is unique. In some patients, there is impaired liver function and hypercholesterolemia.

Differentiation from Sebastian Syndrome
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.

Because of the phenotypic similarities between May-Hegglin anomaly and Fechtner syndrome and the demonstration that the 2 disease loci are mapped to overlapping regions on chromosome 22, the May-Hegglin/Fechtner Syndrome Consortium (2000) suggested that they, as well as Sebastian syndrome, might be allelic. MYH9 was a strong candidate gene because it is located within that region of chromosome 22, is expressed in platelets, and is upregulated during granulocyte differentiation. The May-Hegglin/Fechtner Syndrome Consortium (2000) identified 6 MYH9 mutations (1 nonsense and 5 missense) in 7 unrelated probands from families with one or another of these 3 syndromes.