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.

Low platelet count is rarely caused by inherited thrombocytopenia. May-Hegglin anomaly is an uncommon condition that falls under the umbrella of familial thrombocytopenia. The condition is under-reported in Saudi Arabia; therefore, we report the current case. This is a 24-year-old Saudi lady, presented to the emergency room with vaginal bleeding. No bleeding occurred at any other sites. She has a positive family history of thrombocytopenia among her father and 2 of her siblings. Her platelet count was 16 × 103/µL with normal other blood count as well as renal and liver panels. She was admitted to the regular bed for investigation as sever thrombocytopenia with suspicion of either familial or immune thrombocytopenia. Further studies showed normal hemostatic, virology, and connective tissue disease markers. Peripheral blood film showed low platelet distribution with occasional large/giant platelets and basophilic inclusion bodies in some neutrophils (Dohle body-like). A picture suggestive of May-Hegglin related thrombocytopenia that was confirmed by the presence of a positive myosin heavy chain 9 (MYH9) gene mutation. In conclusion, there are many difficulties in diagnosing and treating May-Hegglin disorders in females of reproductive age. More research and guidelines are needed to manage inherited thrombocytopenia before and throughout pregnancy.

MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital thrombocytopenia, with a risk of developing progressive nephropathy, sensorineural deafness, and presenile cataract. Due to its presentation of isolated thrombocytopenia, it is frequently misdiagnosed as immune thrombocytopenic purpura (ITP). A 10-year-old girl with an initial diagnosis of ITP was evaluated, based on isolated thrombocytopenia and intermittent epistaxis. Clinical assessments included peripheral blood and bone marrow smear examinations to observe cellular morphology. Family history was collected to identify potential hereditary associations. Genetic testing was performed to detect potential pathogenic mutations. Peripheral blood and bone marrow smears revealed giant platelets, along with blue inclusions in neutrophils, eosinophils, and monocytes-key cytological features of MYH9-RD. Family history investigation showed thrombocytopenia in the patient's mother and maternal grandmother; additionally, the mother had mild hearing impairment, and the maternal grandmother had died of renal failure. Genetic testing confirmed the presence of the MYH9 p.E1841K mutation in the patient, which was inherited from her mother. Based on these findings, the diagnosis was revised from ITP to MYH9-RD. This case emphasizes that MYH9-RD should be considered in the differential diagnosis of unexplained thrombocytopenia, particularly when accompanied by characteristic cytological findings (e.g., giant platelets, blue inclusions in leukocytes) and a positive family history of related manifestations. The consistency of phenotypes within the affected family supports the importance of genetic screening and long-term follow-up for relatives of confirmed cases to enable early detection and management of potential complications.

May-Hegglin anomaly (MHA) is a hematologic disorder defined by large platelets (mean platelet volume >12.5 fL) and thrombocytopenia. While it remains unclear whether these patients exhibit clinical coagulopathy, bleeding complications may be confounded in those undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). There are no current guidelines for the perioperative management of patients with MHA. Although some reports favor no treatment, limited case reports have described desmopressin (DDAVP) and platelet transfusion as additional strategies. Thromboelastography® with Platelet Mapping™ (TEG-PM) is one modality capable of monitoring coagulation, which can help guide intraoperative blood product transfusions, particularly in patients with underlying platelet disorders. We report the successful management of a 70-year-old female with a history of MHA who presented for CABG and exhibited persistent bleeding despite adequate heparin reversal with protamine. A post-protamine TEG and TEG-PM were obtained. Prior to sternal closure, platelets were requested to treat ongoing bleeding. While the post-protamine TEG appeared normal, TEG-PM demonstrated platelet inhibition, prompting consideration of DDAVP. As a result, both platelets and DDAVP were administered, leading to hemostasis and cessation of bleeding. Given the limited data, patients with MHA should undergo a thorough perioperative hematologic evaluation, including a history of prior bleeding episodes in addition to conventional laboratory studies. Although an increased risk of hemorrhage has not been definitively demonstrated, preparation with blood products and DDAVP should be considered when a heightened risk of surgical coagulopathy exists, such as during cardiac surgery. In our case, we utilized TEG-PM as an additional tool to evaluate hemostasis, which guided the combined use of platelets and DDAVP. While future studies are needed to assess the utility of TEG-PM in the MHA population, it remains important to consider all available technologies to evaluate potential coagulopathy on an individualized basis.

Introduction: May-Hegglin anomaly (MHA) is a rare autosomal dominant genetic disorder caused by mutations in the MYH9 gene, leading to the presence of Döhle-like inclusions in neutrophils, macrothrombocytes, and thrombocytopenia. This report presents a unique case of a 33-year-old pregnant woman diagnosed with MHA and discusses the diagnostic challenges and management strategies. Case Presentation: A 33-year-old pregnant woman, 17 weeks into her pregnancy, presented with a history of persistent thrombocytopenia. She had previously been diagnosed with immune thrombocytopenia (ITP) and treated with steroids, intravenous immunoglobulin (IVIG), and thrombopoietin receptor agonists (TPO-RA). Her platelet counts had been between 35,000 and 50,000/μL. Upon referral to the hematology clinic, her platelet count was critically low at 15,000/μL, but the mean platelet volume (MPV) remained within normal limits. Despite her low platelet count, her coagulation profile was normal, and physical examination showed no pathological findings. Diagnostic Assessment: The patient's blood smear revealed giant platelets and Döhle-like inclusions in the granulocytes. Genetic testing confirmed a heterozygous mutation in the MYH9 gene, leading to the diagnosis of MHA. Therapeutic Intervention: Due to the risks associated with thrombocytopenia in pregnancy, her prenatal care included routine platelet monitoring and a normal bleeding time assessment. The patient underwent a cesarean delivery under general anesthesia, which resulted in the birth of a healthy baby boy. Conclusion: The case highlights the importance of accurate diagnosis and careful monitoring in managing pregnancy in patients with MHA. A multidisciplinary approach involving obstetricians and hematologists is crucial for optimizing maternal and neonatal outcomes.