Clinical and genetic characteristics of 40 patients with nonmuscle myosin heavy chain 9-related disease (MYH9-RD) misdiagnosed as immune thrombocytopenia: a retrospective analysis in China.

Abstract

Background: Myosin heavy chain 9-related diseases (MYH9-RDs) are rare autosomal dominant platelet disorders characterized by macrothrombocytopenia and leukocyte inclusion bodies. They can manifest with nonhematological complications, including deafness, nephropathy, or cataracts. Due to its rarity and its similar clinical presentation with immune thrombocytopenia (ITP), MYH9-RD is often misdiagnosed as ITP, leading to inappropriate treatment and delayed management of complications.

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

Methods: This multicenter retrospective study included data obtained from Chinese patients diagnosed with MYH9-RD between January 2014 and December 2023 at 5 centers.

Results: Adults exhibited significantly longer median misdiagnosis (9 years vs 0.2 years, P < .001) and treatment durations (1.5 years vs 0.1 years, P < .001) than children. Nonhematological 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 with unknown inheritance patterns. Two novel mutations (p.G1517V and p.K1674Q) were identified. Patients with the p.R702C mutation demonstrated early-stage kidney injury and hearing loss.

Conclusion: Adult patients with MYH9-RD have greater risk of misdiagnosis, prolonged inappropriate treatment, and nonhematological complications than pediatric patients. Enhanced awareness, consideration of mean platelet volume, family history, and genetic screening are crucial for accurate MYH9-RD diagnosis and management. The incidence of spontaneous mutations and identified genotype-phenotype correlations warrant further investigation in the Chinese population.