Clinical and Genetic Characteristics of 40 Patients with Non-Muscle Myosin Heavy Chain 9-Related Disease (MYH9-RD) Misdiagnosed as ITP: A Retrospective Analysis in China.

Background: Myosin Heavy Chain 9-related diseases (MYH9-RD) are rare autosomal dominant platelet disorders characterised by macrothrombocytopaenia and leukocyte inclusion bodies. They can manifest with non-haematological complications, including deafness, nephropathy, or cataracts. Due to its rarity and its similar clinical presentation with immune thrombocytopaenia (ITP), MYH9-RD is often misdiagnosed as ITP, leading to inappropriate treatment and delayed management of complications.

Objective: The study aimed to evaluate clinical, therapeutic, and genetic aspects of patients with MYH9-RD misdiagnosed with ITP, comparing differences between Chinese paediatric and adult cases of this condition.

Methods: This multi-centre retrospective study included data obtained from Chinese patients diagnosed with MYH9-RD between January 2014 and December 2023 at five centres.

Results: Adults exhibited significantly longer median misdiagnosis (9 years vs. 0.2 years, p < 0.001) and treatment durations (1.5 years vs. 0.1 years, p < 0.001) than children. Non-haematological manifestations were exclusive to adults (10/21). All patients received inappropriate ITP treatments, with adults receiving more different treatments. Genetic analysis revealed 21 spontaneous mutations (52.5%), 12 familial mutations, and 7 mutations of unknown inheritance patterns. Two novel mutations (p.G1517V and p.K1674Q) were identified. Patients with p.R702C mutation demonstrated early-stage kidney injury and hearing loss.

Conclusion: Adult patients with MYH9-RD face elevated risks of misdiagnosis, prolonged inappropriate treatment, and non-haematological complications than paediatric patients. Enhanced awareness, consideration of mean platelet volume, family history, and genetic screening are crucial for accurate MYH9-RD diagnosis and management. The prevalence of spontaneous mutations and identified genotype-phenotype correlations warrant further investigation in the Chinese population.