Year : 2009 | Volume
: 20 | Issue : 6 | Page : 1076--1078
Epstein syndrome with rapid progression to end stage renal disease
Esam Alhindawi, Samah Al-Jbour
Pediatric Department, King Hussein Medical Center, Amman, Jordan
Pediatric Department, King Hussein Medical Center, P.O. Box 1643, Tariq, Amman
The association of haematological abnormalities and hereditary nephritis is rare; it is mainly included in a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly, Fechtner, Sebastian, Epstein and Alport syndrome with macro thrombocytopenia. We are presenting a missed case of a boy who presented with epistaxis and his diagnostic work up revealed macrothrombocytopenia, sensorineural hearing loss and chronic nephropathy which constitute the Epstein syndrome, with rapid deterioration of kidney function.
|How to cite this article:|
Alhindawi E, Al-Jbour S. Epstein syndrome with rapid progression to end stage renal disease.Saudi J Kidney Dis Transpl 2009;20:1076-1078
|How to cite this URL:|
Alhindawi E, Al-Jbour S. Epstein syndrome with rapid progression to end stage renal disease. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2020 Aug 3 ];20:1076-1078
Available from: http://www.sjkdt.org/text.asp?2009/20/6/1076/57268
Inherited giant platelet disorders represent a group of rare disorders characterised by thrombocytopenia, giant platelets and variable bleeding symptoms.  All are inherited as autosomal dominant disorders and include: May-Hegglin anomaly, Sebastian, Fechtner, Epstein, and autosomal dominant Alport syndrome with platelet defect.  Epstein syndrome constitute nephritis with no characteristic features associated with nerve conduction deafness and giant thrombocytopenia.  The syndrome belongs to the MYH9 syndromes and was first described in 1972. 
A 10 year old boy presented to the hematology clinic with recurrent epistaxis since early childhood, he was the first child of consanguinous parents, he was known to have mild sensorineural hearing loss since the age of 5 years, and was first found to have thrombocytopenia after investigating him for jaundice and epistaxis and at that time his siblings have acute Hepatitis A infection and he was found to have the same infection as them, the full blood count showed a platelet count of 50-80,000 mm, his WBCs and PCV were normal at that time, and a blood film showed giant form platelets, normochromic normocytic RBCs and normal WBCs with no inclusion bodies. A bone marrow aspirate was done and was normal. He was found to have elevated liver enzymes in the ranges of AST 104, ALT 106 and a liver biopsy was done to rule out liver pathology as a cause of these findings, the liver biopsy showed mild inflammatory cells infil-trate with plasma cells and eosinophils and a work up of liver disease excluded metabolic and autoimmune hepatitis.
He was falling below the third centiles for his height and weight on growth charts and for that a bone age assessment was done and was delayed and showed osteoporotic bone changes, at this point the first urine analysis was done for the patient 1 year after starting investigating him and it showed proteinuria, and hematuria, so was referred to the nephrology clinic for evaluation and there he was found to have blood pressure readings above the 95th centile for his age and height, and his calculated GFR was 65 mL/min/1.73 m, and was considered to have chronic kidney disease and a kidney biopsy was done to diagnose the original pathology, his biopsy findings were consistent with chronic kidney disease with sclerosis and fibrosis in the glomeruli as well as focal loss and atrophy in the tubules [Figure 1].
The patient was screened for hearing and eye abnormalities and his hearing assessment showed bilateral moderate sensorineural hearing loss, and his eye examination was normal. With the findings of chronic nephropathy, giant thrombocytopenia, and sensorineural hearing loss the patient was diagnosed to have Epstein syndrome.
Back to the family history in our patient his mother was known to the Obstetric department because of thrombocytopenia and was diagnosed and followed as a case of chronic idiopathic thrombocytopenic purpura and her blood film contained giant platelets as well, she has normal urine analysis and normal kidney function test with no hearing abnormalities. The father and other siblings were all normal, after diagnosing our patient his mother gave birth to a baby girl who had giant thrombocytopenia and will need follow up for her hearing and kidney function later in life.
To the contrary of what we seen in Alport syndrome our patient showed a rapid deterioration in his kidney function over the last year and was started on hemodialysis recently waiting for completing the tissue matching and other investigations with his father as a possible live related donor for kidney transplant.
The autosomal dominant macrothrombocytopenias which include: May-Hegglin anomaly, Sebastian, Fechtner, Epstein, and autosomal dominant Alport with thrombocytopenia are distinguished by different combinations of clinical and laboratory signs. 
Of the above disorders Epstein syndrome constitute macrothrombocytopenia without neutrophil inclusion bodies in addition to manifestations of deafness and nephritis.  It is an autosomal dominant disease and the hearing and renal abnormalities are indistinguishable from those observed in Fechtner syndrome. 
It belongs to the MYH9 related hereditary macrothrombocytopenia which include the above mentioned disorders  , these pletelets disorders are found to be associated with mutations in the non muscle myosin heavy chain 9 gene (MYH9) which encode non muscle myosin heavy chain IIA (MYHIIA) ,  and this has been located on the chromosome region22q11-q13. 
This disorder was first described by Epstein et al in 1972 when he described two unrelated families with platelet disorder and mild hearing loss as well as renal disease indistinguishable from that of Alport syndrome.  The giant platelets in Epstein syndrome contained granules of normal structure but with an iregular cytoplasm and their survival was normal but the aggregation and excretion in response to collagen, adenosine and thrombin were all decreased,  but the results of platelet dysfunction is variable ranging from normal to grossly impaired,  and the patient usually present with bleeding tendency which is often mild and can be corrected by donor platelet transfusion. Splenectomy does not increase the platelet count,  and steroids has no role in the management of thrombocytopenia in this disorder. 
In Fechtner syndrome the clinical features include the same findings as in Epstein syndrome but in addition there is leucocytes inclusion bodies and eye abnormalities in the form of cataract. 
Patients with Epstein syndrome usually present with renal abnormalities including hematuria, proteinuria, chronic kidney disease, and hypertension or bleeding tendency, the hearing abnormality is usually mild and discovered during routine screening of patients. , The renal abnormalities in Epstein syndrome are variable and has no specific characteristic features with focal segmental glomerulosclerosis being frequently reported as well as features of nephropathy in Alport syndrome,  renal biopsy diagnosis is mandatory in the absence of family members with same features but in the presence of a diagnosed family member it's not necessary and clinical diagnosis suffices. 
We think that our patient is unique for his rapid deterioration of his kidney function since the renal natural history of Epstein syndrome is very similar to Alport syndrome with progression to end stage renal failure in 3rd-4th decade and requirement of renal replacement therapy with both hemodialysis and peritoneal dialysis being suitable modalities of treatment as well as successful renal transplantation. 
So in conclusion it's very important to screen patients with macrothrombocytopenia for urinary abnormalities since the association is very well known, and we also emphasize the importance of a detailed family history in renal problems since hereditary disorders can show different phenotypic features. 
Special acknowledgement to Dr. Issa Hazza'a for his useful suggestions and continued support.
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