Hereditary Thrombocytopenia, Deafness, and Renal Disease

Abstract

The syndrome of hereditary thrombocytopenia, deafness, and renal disease was manifest in at least eight members in three generations of a family. They had a lifelong history of bleeding, usually as epistaxis, bilateral sensorineural deafness starting in late childhood or the teenage years, and persistent proteinuria with varying degrees of renal dysfunction. Two members died at a young age, one from central nervous system hemorrhage, the other from chronic renal failure. Splenectomy and steroid therapy have been of transient benefit. There was dominant inheritance of the syndrome. Hematologic studies showed thrombocytopenia, large platelets, and megakaryocytic hyperplasia of the bone marrow. In contrast to a previous report, our studies showed that affected members had normal in-vitro platelet function and normal ultrastructural platelet morphology. At autopsy, histologic changes in the kidney of one affected family member were indistinguishable from those reported in classic hereditary nephritis with nerve deafness (Alport's syndrome).

Immunofluorescence Analysis of Neutrophil Nonmuscle Myosin Heavy Chain-A in MYH9 Disorders: Association of Subcellular Localization with MYH9 Mutations

“…4). From the first description of EPS as a variant form of Alport syndrome, EPS has been characterized as having no leukocyte inclusion bodies (Eckstein et al, 1975;Epstein et al, 1972). However, our analysis clearly demonstrated that it is merely unrecognizable on standard MGG-stained blood smears.…”

Platelets of the Wistar Furth rat have reduced levels of alpha-granule proteins. An animal model resembling gray platelet syndrome.

“…Large mean platelet volume is a characteristic of several hereditary clinical platelet disorders and anomalies including Bernard-Soulier syndrome (3,4), May-Hegglin anomaly (5,6), gray platelet syndrome (7)(8)(9)(10)(11)(12)(13), Mediterranean macrothrombocytopenia (14)(15)(16)(17), as well as other less well defined thrombocytopathies (18)(19)(20)(21)(22)(23)(24)(25). Of these, Bernard-Soulier syndrome and gray platelet syndrome have well defined platelet biochemical abnormalities: decreased or abnormal glycoprotein Ib-IX complex in the case ofBernard-Soulier syndrome (26)(27)(28)(29)(30)(31)(32), and deficiency of alpha-granule proteins in gray platelet syndrome (9,33,34 (Fig.…”

Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome

“…8 FTNS and EPS, however, manifest a number of nonhematologic traits similar to those observed in Alport syndrome cases, such as nephritis, high-tone sensorineural deafness, and bilateral cataracts, all of which are present with variable expressivity. 1,9,10 The discovery that the genetic loci for all of these syndromes mapped to chromosome 22q12.3 Ϫq13.2, 11-13 and the identification of mutations in the MYH9 gene for each of them, showed that this group of pathologies represent allelic variations of a single genetic disorder. [14][15][16][17][18] MYH9, a 5.8-kb (kilobase) mRNA transcript, encodes for the nonmuscle myosin heavy chain A (also known as NMMHC-A), a large cytoplasmic protein that forms part of the myosin II hexameric complex.…”