MYH9-Related Disease

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: MYH9-related disease (MYH9-RD) is characterized in all affected individuals by hematologic features present from birth consisting of platelet macrocytosis (i.e., >40% of platelets larger than 3.9 μm in diameter), thrombocytopenia (platelet count <150 x 109/L), and aggregates of the MYH9 protein in the cytoplasm of neutrophil granulocytes. Most affected individuals develop one or more additional extrahematologic manifestations of the disease over their lifetime, including sensorineural hearing loss, renal disease (manifesting initially as glomerular nephropathy), presenile cataracts, and/or elevation of liver enzymes.

Diagnosis/testing: The diagnosis of MYH9-related disease is established in a proband with suggestive findings and a heterozygous pathogenic variant in MYH9 identified by molecular genetic testing.

Management: Treatment of manifestations: For most active hemorrhages, consider local measures as the first-line treatment; transfusion of platelet concentrates should be used for active hemorrhages that cannot be otherwise managed, life- or organ-threatening hemorrhages, and/or bleeding at critical sites. Whenever necessary, eltrombopag or platelet transfusion should be used to prepare affected individuals for elective surgery. Antifibrinolytic agents and desmopressin are also used for covering hemostatic challenges or treating hemorrhages. Hearing loss, renal complications, and cataracts are managed in a standard fashion; individuals with severe/profound deafness benefit from cochlear implantation.

Surveillance: For individuals with moderate or severe thrombocytopenia: at least annual (and in case of bleeding and/or changes in bleeding diathesis) microscopic assessment of platelet count and blood count to screen for anemia. Screening for individuals not currently under treatment for the following: annually (or every 6 months in individuals with high-risk MYH9 genotypes) for nephropathy, and every three years for hearing loss, cataracts, and abnormal liver enzymes.

Agents/circumstances to avoid: Drugs that inhibit platelet function or reduce platelet count, and drugs that are ototoxic, nephrotoxic, or hepatotoxic should be used only after assessment of risk-to-benefit ratio. Hazardous noise and activities with high risk of injury should be avoided.

Evaluation of relatives at risk: Clarify the status of all first-degree relatives of an affected individual in order to establish appropriate management (including treatment and surveillance) and awareness of agents and circumstances to avoid.

Pregnancy management: Deliveries should be managed as they are in women with other forms of thrombocytopenia; in general, a platelet count of ≥50 x 109/L is recommended for delivery.

Genetic counseling: MYH9-RD is inherited in an autosomal dominant manner. Approximately 35% of probands represent simplex cases, most of whom have a documented de novo pathogenic variant. Each child of an individual with MYH9-RD has a 50% chance of inheriting the MYH9 pathogenic variant. Once the MYH9 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.

Publication types

  • Review