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 childhood or adult life. For this entity, the term MYH9 -related disease ( MYH9 -RD) has been proposed [ 5 ].