MYH9-related disorders display heterogeneous kidney involvement and outcome

Abstract

Background: MYH9-related diseases (MYH9-RD) are autosomal dominant disorders caused by mutations of the MYH9 gene encoding the non-muscle myosin heavy chain IIA. They are characterized by congenital thrombocytopenia, giant platelets and leucocyte inclusions. Hearing impairment, pre-senile cataract and nephropathy can also occur. We aimed to evaluate renal involvement and outcome in MYH9-RD patients followed-up by nephrologists.

Methods: We conducted a retrospective multicentre observational study of 13 patients among 9 families with MYH9 mutation diagnosed by genetic testing and immunofluorescence assay referred to nephrologists.

Results: At initial referral, median age was 30 (range 14-76) years. Median estimated glomerular filtration rate was 66 mL/min/1.73 m² (0-141) and two patients had already end-stage renal disease (ESRD). Renal presentation associated proteinuria (n = 12), haematuria (n = 6) and hypertension (n = 6). Three patients developed a rapid onset ESRD whereas five others had a relatively stable kidney function over a 3-year median follow-up (1-34). Extra-renal features varied widely, with hearing impairment in six patients, cataract in two and mild liver dysfunction in seven. Thrombocytopenia existed at referral in 11 patients. Time to diagnosis varied from 0 to 29 years (median 3 years). Initial diagnoses such as idiopathic thrombocytopenic purpura (n = 4) and focal segmental glomerulosclerosis (n = 1) led to corticosteroid administration (n = 4), intravenous immunoglobulins (n = 3), cyclophosphamide (n = 1) and splenectomy (n = 1).

Conclusions: Renal involvement and outcome in MYH9-RD are heterogeneous. The diagnosis is often delayed and misdiagnoses can lead to unnecessary treatments. MYH9-RD should be considered in any patient with glomerular involvement associated with a low or slightly decreased platelet count and/or hearing loss and liver dysfunction.

Keywords: FSGS; MYH9; deafness; hereditary nephropathy; thrombocytopenia.

FIGURE 1

Pedigree chart of the Family A. Proband’s (Patient 1) grandfather died at the age of 82 years of so-called ‘uraemia’. The bottom right part of each box (in plain black) corresponds to renal involvement; the bottom left part (in fine stripes) to thrombocytopenia and the upper right part (in large stripes) to hearing disability.