Natural history of the severe subtype of MYH9-related disease (Epstein syndrome)

This study aimed to describe the natural history and genotype-phenotype associations concerning nonhematological complications in Epstein syndrome, a high-risk subtype of MYH9-related disease (MYH9-RD).

We conducted a nationwide cross-sectional study using data from congenital thrombocytopenia registries in Japan. Immunofluorescence analysis and gene testing identified patients with Epstein syndrome carrying high-risk MYH9 variants (R702C/H, S96L). We analyzed the onset and progression of nonhematological complications using Kaplan-Meier survival curves.

Among 177 MYH9-RD patients, 40 had Epstein syndrome with high-risk variants. Over 50 % developed renal failure, deafness, and proteinuria by age 19, increasing to 80 % by age 32. Immunofluorescence detected fine myosin-aggregated granules in neutrophils, which facilitated precise genetic diagnosis. Most cases (95 %) involved de novo variants, highlighting the need for early genetic screening.

Patients with Epstein syndrome are at high risk for developing progressive nonhematological complications. Early detection and intervention are critical for improving outcomes. This study highlights the importance of genetic testing and awareness among healthcare providers to prevent misdiagnosis and delayed treatment.