MYH9related

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in the MYH9 gene, which encodes nonmuscle myosin heavy chain IIA (NMHC-IIA). It encompasses a spectrum of related conditions historically described as May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome. The clinical presentation is highly variable, even within families.

The core hematologic feature is macrothrombocytopenia, with consistently low platelet counts and abnormally large platelets. Bleeding tendency is common, ranging from mild mucocutaneous bleeding to more significant hemorrhage, particularly with surgery or dental procedures. A characteristic finding is the presence of Döhle-like bodies in neutrophils on blood smear. Neutropenia may occur in some individuals, contributing to infection risk.

Non-hematologic manifestations include kidney involvement (proteinuria and progressive renal impairment in a subset of patients), and sensorineural hearing loss that may develop over time. The severity and combination of features vary, and extra-hematologic symptoms do not always accompany the hematologic abnormalities. Inheritance is autosomal dominant, and substantial phenotypic variation can occur among affected relatives.

Diagnosis relies on a compatible clinical/hematologic picture and confirmation by genetic testing for MYH9 mutations. Blood smear showing large platelets with Döhle-like neutrophil inclusions supports the diagnosis; sequencing can identify the causative MYH9 variant.

Management is supportive and multidisciplinary. It focuses on bleeding risk reduction (avoiding NSAIDs, planning before procedures), potential platelet transfusions for significant bleeds, and monitoring renal and auditory function. Genetic counseling is recommended due to the inherited nature of the condition. Prognosis is variable, with some individuals maintaining normal function and others developing progressive organ involvement.