Hereditary nephritis with macrothrombocytopenia: phenotypic variety and the genotypic defect

A number of patients present to nephrologists with end-stage renal failure of unknown cause and many have small kidneys, making renal biopsy inadvisable. A small number may have clues to the diagnosis of hereditary nephritis, as in the patient we present here. The propositus was a 22-year-old man, who was admitted to our nephrology ward because of recently discovered renal insufficiency. Ultrasound examination revealed bilateral small kidneys. He was severely hypertensive; audiometry and ophthalmic examinations were normal. Thrombocytopenia with giant platelets was observed in peripheral blood smears. Basophilic cytoplasmic inclusions (Döhle-like bodies) were present in neutrophil and basophilic granulocytes. A family history of nephropathy associated with macrothrombocytopenia was obtained. Epstein syndrome was diagnosed, a rare autosomal dominant disorder. He started hemodialysis and subsequently received a living donor kidney transplant (from his mother). Molecular genetics has considerably clarified the field of hereditary nephritis associated with macrothrombocytopenia by demonstrating that these syndromes involve a similar molecular defect. It was first shown that these syndromes were linked to the same locus on chromosome 22q. Then the gene involved--encoding non-muscle myosin heavy chain 9 (MYH9)--was identified. This entity ("MYH9 disease") must be clearly differentiated from Alport syndrome (type IV collagen disease). In conclusion, this case serves to remind us: 1) that in patients presenting late to nephrologists with bilateral small kidneys, the diagnosis can still be made in some instances on the basis of other clinical signs known to be associated with recognized inherited syndromes; 2) that there are various types of inherited thrombocytopenia associated with nephritis; screening for nephritis is mandatory in all of them.