Renin-angiotensin system blockade is effective in reducing proteinuria of patients with progressive nephropathy caused by MYH9 mutations (Fechtner-Epstein syndrome)

Abstract

Fetchner syndrome (FTNS, OMIM 153640) is an autosomal dominant disorder characterized by the association of macrothrombocytopaenia, leukocyte inclusions, sensorineural deafness, cataracts and nephropathy often leading to end-stage renal disease (ESRD) [1]. Epstein syndrome (EPTS, OMIM 153650) presents the same features of FTNS, with the exception of leukocyte inclusions and cataracts [2]. Recently, it was shown that both FTNS and EPTS derive from mutations of MYH9, the gene for the heavy chain of non-muscle myosin IIA [3,4]. The same gene was found to be also responsible for two non-syndromic forms of inherited macrothrombocytopaenia with leukocyte inclusions, May-Hegglin anomaly (MHA, OMIM 155100) and Sebastian syndrome (SBS, OMIM 605249) [3]. Further studies demonstrated that patients initially diagnosed as having MHA/SBS can subsequently develop nephropathy, deafness and/or cataracts, while affected relatives of FTNS or EPTS patients present for all their lifetime a clinical picture indistinguishable from that of MHA/SBS subjects [5]. Moreover, immunofluorescence studies showed that leukocyte inclusions containing the MYH9 protein are present not only in MHA/SBS and FTNS, but also in all patients with EPTS [5]. Therefore, it was clear that FTNS, EPTS, MHA and SBS are not distinct entities, but rather they represent different clinical presentations of a single disease, characterized by the constant finding of congenital thrombocytopaenia and leukocyte inclusions, and possible development of nephropathy, deafness and/or cataracts in