Introduction: MYH9-related disorders are rare inherited platelet disorders which are characterized by macrothrombocytopenia with or without leucocyte inclusion bodies. Four autosomal dominant clinical syndromes May-Hegglin, Fechtner, Epstein, and Sebastian, characterized by macrothrombocytopenia, in addition to one or more of neutrophil Döhle-like bodies, sensorineural deafness, cataracts, and glomerular abnormalities. Nephropathy affects 25–37% of patients with MYH9-RD.Diagnosis relies on the presence of immunofluorescent-positive NMMHC-IIA aggregates in neutrophils and genetic testing which is often misdiagnosis which may result to unnecessary treatment.

Methods We conducted a retrospective analysis of 16 of MYH-9 mutation patients of Arab ethnicity, focusing on demographics, clinical features, laboratory results, treatments, and outcomes.

Result: It is a retrospective analysis of 16 patients who had MYH9-RD at a median age of 19 years (range: 1.8–49 years). The cohort consisted of 10 (62.5%) female and 6 (37.5%) male patients, while 7(43.7%) were identified as consanguineous. MYH9 mutation was heterozygous genotypes in 11(68.7%) patients, whereas 5 (31.2%) %) patients were homozygous. Thrombocytopenia was seen in 13 (81.3) cases, with a median platelet count of 57 ×10⁹/L (range: 6–360 ×10⁹/L). Giant platelets were observed in 10 patients (62.5%), and Döhle like bodies were identified in 3 patients (18.7%). Eight (50%) cases presented with bleeding. Three cases experienced epistaxis and bruising, one patient had per vaginal bleeding and recurrent miscarriages, while another developed an intracranial hemorrhage which responded well to platelet transfusion. Three (18.7%) patients developed sensorineural hearing loss and six patients (37.5%) presented with ocular abnormalities, including cataract, myopia or astigmatism. Renal involvement was observed in seven patients (41%). Of these, five progressed to end-stage renal disease (ESRD), requiring either dialysis or kidney transplantation. The renal biopsies of 4 patients showed C3-predominant glomerulopathy, minimal change disease and focal segmental glomerulosclerosis. Among these patients, 5 recived Eltrombobag, a thrombopoietin receptor agonist, which improved platelet counts. Three patients underwent successful living-related kidney transplantation with perioperative platelet transfusions, and no significant bleeding complications were observed. One patient received matched sibling donor stem cell transplantation for treating coexisting aplastic anemia.

Two cases showed atypical presentations that did not fully meet the established criteria for MYH9-related syndrome, as both exhibited all clinical features except cataract. One patient carried the c.2104C>T (p.Arg702Cys) mutation variant, which is associated with a severe disease phenotype. She had single-digit platelet counts and experienced nine pregnancy losses. Initially misdiagnosed and treated for immune thrombocytopenic purpera (ITP) for 17 years, she underwent a renal transplant at age 27, followed by a second transplant at age 30 due to graft rejection. The patient achieved normal platelet counts after receiving Eltrombopag as a treatment. This case showed that diagnosis of MYH9-RD is often delayed and misdiagnoses can lead to unnecessary treatments.

Conclusion: This series highlights the diverse clinical spectrum of MYH9-RD. Early recognition and multidisciplinary management are essential to address extra-hematological manifestations, such as kidney ,ear and ocular involvement. Bleeding is generally mild but can be clinically significant during surgery, obstetric settings, or invasive procedures which require urgent intervention. Targeted therapies and supportive measures, including eltrombopag and renal transplantation, can achieve favorable outcomes in selected patients. Further studies are needed to explore the role of TPO agonists in MYH9-RD.

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2025
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