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At a glance

A genetic disorder characterized by platelet disorder (thrombocytopenia with giant platelets), nephritis and subsequently renal failure, and sensorineural deafness. The renal and hearing abnormalities are indistinguishable from those observed in Fechtner Syndrome and Alport Syndrome (see “Other conditions to be considered”).

Synonyms

Alport-like Macrothrombocytopenia Syndrome; Alport Syndrome Type V; Macrothrombocytopathy, Nephritis, Deafness Syndrome.

N.B.: Epstein Syndrome can also refer to a disorder associated with splenomegaly, high platelet count, and prolonged bleeding time. This disorder has also been termed Di Guglielmo Disease II or Di Guglielmo Syndrome, Epstein-Goedel Syndrome, Mortensen Disease/Syndrome, or Revol Disease/Syndrome.

History

First reported in two families by Charles J. Epstein (1933-2011) in 1972. Dr Epstein was a geneticist at the University of California, San Francisco and the Buck Institute for Age Research, in 1972. Dr Epstein was severely injured in 1993 when he became a victim of a mail bomb attack by the Unabomber.

Incidence

Unknown; however, more than 30 families have been reported. No sexual predilection has been reported.

Genetic inheritance

Autosomal dominant with the genetic defect mapping to 22q11.2. It is suspected that a MYH9 mutation contributes to the various inherited giant platelet disorders.

Pathophysiology

The bleeding tendency is a result of thrombocytopenia and the presence of a majority of giant spheroid platelets with a disorganized microtubular system and a lesser number of normal-size discoid platelets. Renal dysfunction occurs secondary to proliferative and sclerosing glomerulonephritis with interstitial nephritis and fibrosis. Hearing loss is gradual and of sensorineural etiology.

Diagnosis

Based on family history, clinical features, hematologic and nephrologic studies, and auditory examination. Hematologic studies reveal thrombocytopenia, prolonged bleeding time, and the above described giant platelets with abnormal ultrastructure, impaired platelet aggregation response to collagen and epinephrine, defective platelet adherence to glass, and impaired release of platelet factor III. The renal abnormality mainly manifests as proteinuria, which remains stable with normal renal function, although deterioration as a result of episodes of acute glomerulonephritis has been described.

Clinical aspects

Patients may develop multiple ecchymoses when they start walking and recurrent episodes of epistaxis beginning in early childhood. Bleeding from other sites is rare and usually not significant. High-frequency sensorineural hearing loss becomes noticeable by approximately 5 to 8 years of age, and progression to almost complete deafness may occur around the middle of the second decade of life. Proteinuria begins in childhood, usually without impairment of renal excretory function. In rare cases, episodes similar to acute glomerulonephritis occur.

Precautions before anesthesia

Laboratory investigations should include a complete blood count and coagulation studies, including bleeding time, platelet count, and a blood smear (thrombocytopenia and ultrastructural and functional studies ...

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