Clinical and Molecular Spectrum of MYH9-Thrombocytopenia: Insights from a Single Centric Pediatric Cohort.

Background

MYH9-related disease (MYH9-RD) is the most common form of inherited thrombocytopenia (IT). It is caused by pathogenic variants in the MYH9 gene. It manifests as early-onset macrothrombocytopenia with variable later-onset extra-hematological features, including hearing loss, renal disease, and cataracts. In pediatric patients, early recognition is critical to avoid misdiagnosis as immune thrombocytopenia (ITP) and unnecessary immunosuppressive therapy.

Methods

We conducted a retrospective unicentric study at the Pediatric Oncology and Hematology Department, Fundeni Clinical Institute, Bucharest, Romania, including patients aged 0-18 years with suspected IT, tested between 2017 and 2025 by next-generation sequencing (NGS). Clinical, laboratory, and genetic data were reviewed.

Results

Among 66 patients who underwent genetic testing, 31 (48.5%) had IT-associated genetic variants; 8 (25.8%) carried MYH9 mutations. Four patients (50%) had disease onset before age 1 year, three with neonatal presentation; 3 (37.5%) reported a family history of thrombocytopenia. Six variants were previously reported, and two were novel variants. Five variants (62.5%) were pathogenic, while three (37.5%) were initially classified as variants of uncertain significance (VUS). Most mutations were missense in the coiled-coil tail domain, correlating with milder thrombocytopenia and absence of extra-hematological features. No life-threatening bleeding was recorded; hemorrhagic symptoms were limited to minor mucocutaneous bleeding.

Conclusions

This is the first Romanian pediatric cohort and one of the few existing pediatric cohorts describing the genetic and clinical spectrum of MYH9-RD. Early genetic confirmation enables precise diagnosis, tailored management, and family screening, while preventing inappropriate therapies.