A novel variant of MYH9 mutation associated macro-thrombocytopenia: A case series

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder characterized by macro-thrombocytopenia and variable extra-hematological manifestations including sensorineural hearing loss (SNHL), nephropathy, and cataracts. Due to its phenotypic overlap with immune thrombocytopenia (ITP), it is often misdiagnosed, leading to inappropriate treatment.

To report a novel MYH9 gene variant in a family with syndromic macro-thrombocytopenia and to highlight the therapeutic benefit of thrombopoietin receptor agonists in symptomatic individuals.

The index case, a 22-year-old male with mucocutaneous bleeding and bilateral SNHL, showed poor response to corticosteroids. NGS identified a novel heterozygous variant in the MYH9 gene (c.130_131delinsAA; p.Ala44Asn), located in the conserved head domain of NMMHC-IIA. The variant segregated in four other affected family members, two of whom had SNHL and one had cataract. Symptomatic individuals treated with Eltrombopag achieved sustained improvements in platelet counts and resolution of bleeding.

This report identifies a novel pathogenic MYH9 variant associated with syndromic macro-thrombocytopenia and emphasizes the importance of recognizing inherited thrombocytopenia. Early diagnosis avoids unnecessary immunosuppression and allows for appropriate use of thrombopoietin receptor agonists, genetic counselling, and surveillance for extra-hematological complications.