MYH9-related syndromic thrombocytopenia

MYH9-related syndromic thrombocytopenia (Orphanet code 182050) is a group of rare inherited disorders caused by mutations in the MYH9 gene, which encodes non-muscle myosin heavy chain IIA. This condition encompasses several previously distinct clinical entities, including May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome, now recognized as a single disease spectrum collectively referred to as MYH9-related disease (MYH9-RD). The hallmark feature present from birth is macrothrombocytopenia — a reduced number of abnormally large platelets — which can lead to variable bleeding tendencies ranging from mild bruising to more significant hemorrhage. Beyond the hematologic manifestations, MYH9-related syndromic thrombocytopenia can affect multiple organ systems over time. Key non-hematologic complications include sensorineural hearing loss, which may develop during childhood or adulthood and can be progressive; nephropathy, which can range from mild proteinuria to progressive kidney disease potentially leading to end-stage renal failure; and presenile cataracts. Characteristic Döhle-like inclusion bodies (aggregates of abnormal myosin) may be observed in neutrophils on peripheral blood smear, which is an important diagnostic clue. The severity and combination of these features vary considerably among affected individuals, even within the same family. Diagnosis is confirmed through genetic testing identifying pathogenic variants in MYH9. Management is primarily supportive and symptom-based. Platelet transfusions may be required for significant bleeding episodes or prior to surgical procedures, though many patients have only mild bleeding symptoms. Hearing aids or cochlear implants may be needed for hearing loss. Nephropathy requires monitoring and standard renal protective measures, and kidney transplantation may be necessary in severe cases. Cataract surgery can address visual impairment. Importantly, the thrombocytopenia in MYH9-RD is often misdiagnosed as immune thrombocytopenia (ITP), leading to unnecessary treatments such as corticosteroids or splenectomy, which are ineffective in this condition. Eltrombopag, a thrombopoietin receptor agonist, has shown some efficacy in increasing platelet counts in certain patients.

Common questions about MYH9-related syndromic thrombocytopenia