SciELO - Scientific Electronic Library Online

vol.40 issue2Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitisThe enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand




Related links


Brazilian Journal of Nephrology

Print version ISSN 0101-2800On-line version ISSN 2175-8239

J. Bras. Nefrol. vol.40 no.2 São Paulo Apr./June 2018  Epub May 17, 2018 

Case Reports

Macrothrombocytopenia, renal dysfunction and nephrotic syndrome in a young male patient: a case report of MYH9-related disease

Gabriela Sevignani1 

Giovana Memari Pavanelli1 

Sibele Sauzem Milano1 

Bianca Ramos Ferronato2 

Maria Aparecida Pachaly1 

Hae II Cheong3 

Mauricio de Carvalho2 

Fellype Carvalho Barreto1 

1Universidade Federal do Paraná, Departamento de Medicina Interna, Divisão de Nefrologia, Curitiba, PR, Brasil.

2Universidade Federal do Paraná, Hospital das Clínicas, Departamento de Medicina Interna, Curitiba, PR, Brasil.

3Seoul National University, Children's Hospital, Department of Pediatrics, Seoul, Korea.


MYH9-related disease is an autosomal dominant disorder caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA on chromosome 22q12. It is characterized by congenital macrothrombocytopenia, bleeding tendency, hearing loss, and cataracts. Nephropathy occurs in approximately 30% of MYH9-related disease in a male patient carrier of a de novo missense mutation in exon 1 of the MYH9 gene [c.287C > T; p.Ser(TCG)96(TTG)Leu]. He presented all phenotypic manifestations of the disease, but cataracts. Renal alterations were microhematuria, nephrotic-range proteinuria (up to 7.5 g/24h), and rapid loss of renal function. The decline per year of the glomerular filtration rate was 20 mL/min/1.73m2 for five years. Blockade of the renin-angiotensin system, the only recommended therapy for slowing the progression of this nephropathy, was prescribed. Although MYH9-related disease is a rare cause of glomerulopathy and end-stage renal disease, awareness of rare genetic kidney disorders is essential to ensure accurate diagnosis and proper management of orphan disease patients.

Keywords: Renal Insufficiency, Chronic; Thrombocytopenia; Nephrotic Syndrome; Genetic Diseases, Inborn; Rare Diseases


MYH9-related disease (MYH9-RD) is a genetic disorder of autosomal dominant inheritance caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA (NMMHC-IIA) on chromosome 22q12. Around 200 affected families have been described in the literature, which suggest a very low prevalence of this disease.

MYH9-RD is characterized by congenital macrothrombocytopenia, leading to bleeding tendency, along with cytoplasmic inclusion bodies within leukocytes (Döhle-like inclusions), sensorineural deafness, cataracts, and nephropathy. The latter usually presents at a juvenile age with proteinuria, sometimes causing nephrotic syndrome, with or without microhematuria. It often progresses to end-stage renal disease (ESRD).1

Herein, we sought to describe the case of a young male patient affected by MYH9-RD that developed nephrotic-range proteinuria, microhematuria, and rapid loss of kidney function.


A twenty-year-old male has been followed up at the Clinic Hospital of Federal University of Paraná due to medical history of epistaxis, ecchymosis, and petechiae since infancy. At first, Bernard-Soulier syndrome was suspected due to macrothrombocytopenia and tendency of bleeding. When he was 17 years old, hearing loss and hypertension were detected along with mild renal failure, microhematuria and nephrotic-range proteinuria. Renal biopsy could not be performed due to risk of bleeding (platelets count: 7000/µL). Cataracts were excluded by ophthalmological evaluation. Due to the clinical suspicion of MYH9-RD, genotyping of the patient and of his parents was performed. A de novo missense mutation in exon 1 of the MYH9 gene [c.287C > T; p.Ser(TCG)96(TTG)Leu] was detected (Figure 1). Actually, neither his parents nor his brother and sister had clinical manifestation of MYH9-RD. Enalapril (20 mg/day) was initiated for renal protection. The patient did not adhere to treatment and was lost to follow-up. Two years later, he returned to the outpatient clinic complaining of foamy urine, peripheral edema, and hypertension (160/120 mmHg). Laboratory tests detected worsening of renal function and persistent proteinuria. Table 1 shows the evolution of laboratory parameters during the follow-up.

Figure 1 Molecular test of the index case and of his parents; Footnote: a de novo heterozygous c.287C>T in exon 1 of MHY9 [p.Ser(TCG)96(TTG) Leu] was detected (i). His father (ii) and his mother (iii) did not have the mutation. 

Table 1 Laboratory evolution. 

Laboratory June 2012 March 2013 June 2015 June 2017
creatinine (mg/dL) 0.9 1.2 1.7 3.4
eGFR (mL/min/1.73m2) 126 88.4 57.2 24.4
urea (mg/dL) 34 27 32 80
proteinuria (g/24h) NA 7.5 5.5 5.7
albumin (g/dL) 3.4 3.1 3.5 3.1
cholesterol (mg/dL) 185 205 249 241
platelets count (n/µL) 4000 7000 6500 3000

Abbreviations: eGFR: CKD-EPI estimated glomerular filtration rate; NA: not available.


MYH9-RD is characterized by congenital macrothrombocytopenia associated with variable degrees of sensorineural hearing loss, pre-senile cataract, and renal disease. Nephropathy occurs in approximately 30% of the patients with MYH9-RD and has a progressive and severe evolution. It usually presents at a juvenile age with proteinuria, sometimes causing nephrotic syndrome, with or without microhematuria. Our patient presented all clinical manifestation of MYH9-RD, but cataract. In most patients, nephropathy progresses to ESRD before the fourth decade of life.1

A genotype-phenotype correlation has been recognized in MYH9-RD. A higher incidence and a worse prognosis of kidney impairment have been associated with mutations affecting the head domain of NMMHC-IIA, compared with mutations in tail domain.2 Most patients with MYH9-RD present an autosomal dominant inheritance, and around 30% of them have a de novo mutation.1 Our patient presented a de novo missense mutation in exon 1 of MYH9 [c.287C > T; p.Ser(TCG)96(TTG)Leu] in the head domain. To date, more than 30 mutations within the 40 exons of the MYH9 gene have been detected, among them the one of our patient.3 In agreement with the genotype-phenotype correlation, our patient developed a rapid deterioration of renal function. The decline per year of the glomerular filtration rate was 20 mL/min/1.73m2 during the last five years.

Due to the overlap of clinical manifestations, MYH9-RD associated with renal impairment was considered a variant of Alport syndrome, designated as Fechtner syndrome. Recently, these syndromes were recognized as distinct disorders. They can be distinguished by the presence of thrombocytopenia, the hallmark of MYH9-RD and not a feature of Alport syndrome. Moreover, the latter is caused by mutations in the COL4A3, COL4A4, and COL4A5 genes, leading mainly to alterations in the glomerular basement membrane.4 The clinical features together with the presence of a pathogenic mutation in the MYH9 gene allowed a prompt and reliable diagnosis of MYH9-RD.

Renal biopsy is not usually performed in MYH9-nephropathy because of the risk of bleeding, reserved for cases in which the differential diagnosis is necessary. Renal histopathological findings are variable and unspecific, encompassing mesangial expansion or proliferation and segmental glomerulosclerosis. Electron microscopy commonly reveals glomerular basement membrane thickening and podocyte foot process effacement1. The pathogenesis of MYH9-nephropathy is not completely understood. NMMHC-IIA is an important component of podocyte foot process. Thus, MYH9-nephropathy may result from an alteration in the podocyte cytoskeleton.5

Blockade of the renin-angiotensin system might be effective in reducing proteinuria and slowing the progression of MYH9 nephropathy.6 As our patient did not adhere to the treatment, we could not evaluate the efficacy of this strategy, though.

To the best of our knowledge, this is the first case of MYH9-nephropathy described in Brazil. The learning points of this case need to be highlighted. In case of macrothrombocytopenia of uncertain diagnosis, urinalysis must be performed and proteinuria should be monitored to start renin-angiotensin system blockage as early as possible. Genotyping is a valuable tool for guiding diagnosis and prognosis. Finally, awareness of rare genetic kidney disorders is essential to ensure accurate diagnosis and proper management of orphan disease patients.


This study was carried out at the Clinic Hospital of the Federal University of Paraná and supported by a grant (HI12C0014) from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea.


1 Oh T, Jung Seo H, Taek Lee K, Jo Kim H, Jun Kim H, Lee JH, et al. MYH9 nephropathy. Kidney Res Clin Pract 2015;34:53-6. [ Links ]

2 Pecci A, Klersy C, Gresele P, Lee KJ, De Rocco D, Bozzi V, et al. MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations. Hum Mutat 2014;35:236-47. [ Links ]

3 Arrondel C, Vodovar N, Knebelmann B, Grünfeld JP, Gubler MC, Antignac C, et al. Expression of the nonmuscle myosin heavy chain IIA in the human kidney and screening for MYH9 mutations in Epstein and Fechtner syndromes. J Am Soc Nephrol 2002;13:65-74. [ Links ]

4 Savige J, Storey H, Il Cheong H, Gyung Kang H, Park E, Hilbert P, et al. X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations. PLoS One 2016;11:e0161802. [ Links ]

5 Bostrom MA, Freedman BI. The spectrum of MYH9-associated Nephropathy. Clin J Am Soc Nephrol 2010;5:1107-13. [ Links ]

6 Pecci A, Granata A, Fiore CE, Balduini CL. Renin-angiotensin system blockade is effective in reducing proteinuria of patients with progressive nephropathy caused by MYH9 mutations (Fechtner-Epstein syndrome). Nephrol Dial Transplant 2008;23:2690-2. [ Links ]

Received: August 01, 2017; Accepted: August 18, 2017

Correspondence to: Fellype Carvalho Barreto. E-mail:

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.