Background/Objectives: MYH9 gene variants cause MYH9-related disease (MYH9-RD), which is also known as Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, and Sebastian syndrome. MYH9-RD is characterized by sensorineural hearing loss, macrothrombocytopenia, thrombocytopenia, hematuria/proteinuria, glomerulonephritis, cataracts purpura, and mucosal bleeding. In addition, the MYH9 gene is also known to be causative of autosomal dominant non-syndromic hearing loss (DFNA17). MYH9-RD is a relatively rare disorder, and the detailed clinical features and mutational spectra remain unclear. Methods: In this study, we performed next-generation sequencing analysis for 15,684 hearing loss patients and identified MYH9-associated hearing loss patients. Detailed clinical information was collected for these patients and summarized. Results: In this study, we identified 24 patients from 18 families with MYH9-associated hearing loss. We clarified the details of hearing deterioration observed in patients based on collected serial audiogram data. Some cases showed rapid hearing deterioration that worsened by about 50 dB within 5 years. Hearing loss is more likely to progress in patients with myosin head domain variants than in patients with myosin tail domain variants, but hearing loss in each set of patients finally deteriorates to bilateral profound hearing loss. Conclusions: In this study, we were able to clarify the detailed characteristics of MYH9-RD- and DFNA17-related hearing loss in a relatively large number of patients, particularly in some cases that showed rapid and asymmetrical hearing deterioration progressing to bilateral profound hearing loss. Our data will be useful for providing more appropriate treatment and follow-up for MYH9-associated hearing loss.

Myosin heavy chain 9-related disease (MYH9-RD) is a rare inherited disorder characterised by macrothrombocytopenia, often misdiagnosed as immune thrombocytopenia (ITP). Early identification is crucial to prevent unnecessary treatments and to ensure appropriate monitoring. The present case aims to highlight the diagnostic challenges and clinical management of MYH9-RD in a toddler, emphasising the importance of early genetic testing. We discuss a 13.5-month-old girl with macrothrombocytopenia lacking Döhle bodies, who initially received intravenous immunoglobulin (IVIg) and corticosteroids without any response. Within two months, whole-exome sequencing identified a pathogenic MYH9 mutation (c.287C>T; p.Ser96Leu). One year later, the patient remains clinically stable without significant bleeding. The occurrence of petechial rash exhibited a more pronounced correlation with platelet mass index (PMI) values compared to platelet count (PLT), underscoring its significance in clinical evaluation. MYH9-RD should be considered in cases of IVIg-resistant thrombocytopenia accompanied by macrothrombocytes. Timely genetic testing can facilitate accurate diagnosis and may help avoid unnecessary procedures, while routine renal and auditory monitoring is important for managing the S96L variant.

MYH9-related disease (MYH9-RD) is an autosomal dominant disorder typically characterized by macrothrombocytopenia, leukocyte inclusion bodies, and variable non-hematologic manifestations such as hearing loss and nephropathy. We herein describe a 16-year-old boy presenting with persistent proteinuria and biopsy-proven membranous nephropathy with focal segmental sclerosis. Genetic testing identified a rare MYH9 variant (p.I1816V), previously reported in association with Epstein syndrome. However, the patient had normal platelet counts, no leukocyte inclusions, and no abnormalities in non-muscle myosin heavy chain IIA (NMMHC-IIA) expression in neutrophils or podocytes. Although globally rare, the p.I1816V variant is more frequent in East Asian populations and is predicted to be benign by multiple in silico tools. This case illustrates the challenges of interpreting rare variants in the absence of supportive clinical findings and highlights the need for cautious evaluation in the era of next-generation sequencing.

We report the case of a 24-year-old patient affected by Epstein syndrome, in whom a CT scan performed in a traumatic context revealed numerous splenic lesions. After hemostatic splenectomy, the pathological examination showed splenic well-limited, non-encapsulated nodules, consisting of dilated venous sinuses, filled with red blood cells with inter-connected anfractuous vascular structures. These lesions had the following double endothelial and histiocytic immunohistochemical profile: CD31+, Factor VIII+, CD34+, ERG+, D2/40-, CD68+, CD21+/-. This is the second case reported in the literature of littoral cell angioma in association with Epstein syndrome.