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MYH9-related disease

Synonym(s) MYH9-RD
MYH9-related disorder
MYH9-related syndrome
MYH9-related syndromic thrombocytopenia
Prevalence 1-9 / 1 000 000
Inheritance Autosomal dominant
Age of onset Neonatal
  • D69.4
MeSH -
MedDRA -


Disease definition

MYH9-related disease (MYH9-RD) is an inherited giant platelet disorder with a complex phenotype characterized by congenital thrombocytopenia and possible subsequent manifestations of sensorineural hearing loss, presenile cataracts, elevation of liver enzymes, and/or progressive nephropathy often leading to end-stage renal disease (ESRD). Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly and Sebastian syndrome, previously described as distinct disorders, represent some of the different clinical presentations of MYH9-RD.


Prevalence in Italy is estimated at 1/400,000-1/300,000. More than 300 MYH9-RD pedigrees have been reported worldwide.

Clinical description

Thrombocytopenia is present at birth and can be associated with spontaneous bleeding (usually mild or moderate). Bleeding symptoms include easy bruising, epistaxis, gum bleeding, and/or menorrhagia. Life-threatening hemorrhage is rare. Patients have an increased risk of hemorrhages after surgery, biopsy, or deliveries. Hearing loss is seen in almost all cases with the age of onset ranging from the 1st to 6th decade and the severity of hearing loss varying greatly (from mild defects to profound deafness). Proteinuric nephropathy occurs in about 30% of patients and in 75% is diagnosed before the age of 35. The majority of patients with kidney damage progress to ESRD within a few years. Patients that develop kidney involvement later in life often have a slower progression towards ESRD. Cataracts occur in about 20% of patients, are often bilateral and usually appear in early adulthood, but congenital cases have been reported.


MYH9-RD is due to mutations in the MYH9 gene (22q13.1), encoding the heavy chain of the isoform A of the non-muscle myosin of class II (myosin-9). Myosin-9 is expressed in most cell types and tissues, including blood cells, cochlea, kidney, and hepatocytes. Neutrophil inclusions originate from co-precipitation of mutant myosin-9 with wild-type proteins within the cytoplasm.

Diagnostic methods

Diagnosis is suspected on hematological findings and possible association with extra-hematological manifestations. Diagnosis is confirmed by immunofluorescence assay on peripheral blood slides revealing typical myosin-9 neutrophil inclusions. Kidney damage is revealed by proteinuria with or without renal failure. Audiometric and ophthalmologic examinations identify a hearing defect and/or cataract, respectively. About 50% of patients have chronic or intermittent elevation of liver enzymes. Molecular genetic testing can identify the causative MYH9 mutation, which can predict the clinical evolution.

Differential diagnosis

Differential diagnoses include Bernard-Soulier syndrome, Alport syndrome and immune thrombocytopenia purpura (see these terms).

Antenatal diagnosis

Prenatal diagnosis is possible in families where a disease causing mutation has been identified.

Genetic counseling

MYH9-RD is inherited in an autosomal dominant manner with sporadic de novo mutations also being observed. Genetic counseling is possible.

Management and treatment

In cases of severe hemorrhages or before major hemostatic stresses (pregnancy, surgery), platelet transfusions (when possible from HLA-matched donors) are recommended. Eltrombopag has been successful in increasing platelet counts and abolishing the tendency to bleed. Desmopressin can shorten bleeding time in some patients; a test dose should be given to observe responsiveness. Surgery treats cataracts. A cochlear implant was beneficial in one patient with severe deafness. Angiotensin receptor blockers and/or angiotensin-converting enzyme inhibitors may reduce proteinuria in those with renal involvement. ESRD requires treatment with dialysis or kidney transplantation. Regular blood counts, annual urine analysis as well as audiometric and ophthalmologic evaluations are recommended. Medications that interfere with platelet function should be avoided.


Overall life-expectancy is not affected. Quality of life can be seriously affected in patients who develop kidney involvement and deafness, as well as in rare cases with severe spontaneous bleeding.

Expert reviewer(s)

  • Dr Alessandro PECCI

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Detailed information

Review article
Clinical practice guidelines
Clinical genetics review
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