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MYH9-related disorder

Reviewed April 2011

What is MYH9-related disorder?

MYH9-related disorder is a condition that can have many signs and symptoms, including bleeding problems, hearing loss, kidney (renal) disease, and clouding of the lens of the eyes (cataracts).

The bleeding problems in people with MYH9-related disorder are due to thrombocytopenia. Thrombocytopenia is a reduced level of circulating platelets, which are cell fragments that normally assist with blood clotting. People with MYH9-related disorder typically experience easy bruising, and affected women have excessive bleeding during menstruation (menorrhagia). The platelets in people with MYH9-related disorder are larger than normal. These enlarged platelets have difficulty moving into tiny blood vessels like capillaries. As a result, the platelet level is even lower in these small vessels, further impairing clotting.

Some people with MYH9-related disorder develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). Hearing loss may be present from birth or can develop anytime into late adulthood.

An estimated 30 to 70 percent of people with MYH9-related disorder develop renal disease, usually beginning in early adulthood. The first sign of renal disease in MYH9-related disorder is typically protein and/or blood in the urine. Renal disease in these individuals particularly affects structures called glomeruli, which are clusters of tiny blood vessels that help filter waste products from the blood. The resulting damage to the kidneys can lead to kidney failure and end-stage renal disease (ESRD).

Some affected individuals develop cataracts in early adulthood that worsen over time.

Not everyone with MYH9-related disorder has all of the major features. All individuals with MYH9-related disorder have thrombocytopenia and enlarged platelets. Most commonly, affected individuals will also have hearing loss and renal disease. Cataracts are the least common sign of this disorder.

MYH9-related disorder was previously thought to be four separate disorders: May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome. All of these disorders involved thrombocytopenia and enlarged platelets and were distinguished by some combination of hearing loss, renal disease, and cataracts. When it was discovered that these four conditions all had the same genetic cause, they were combined and renamed MYH9-related disorder.

How common is MYH9-related disorder?

The incidence of MYH9-related disorder is unknown. More than 200 affected families have been reported in the scientific literature.

What genes are related to MYH9-related disorder?

MYH9-related disorder is caused by mutations in the MYH9 gene. The MYH9 gene provides instructions for making a protein called myosin-9. This protein is one part (subunit) of the myosin IIA protein.

There are three forms of myosin II, called myosin IIA, myosin IIB and myosin IIC. The three forms are found throughout the body and perform similar functions. They play roles in cell movement (cell motility); maintenance of cell shape; and cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. While some cells use more than one type of myosin II, certain blood cells such as platelets and white blood cells (leukocytes) use only myosin IIA.

MYH9 gene mutations that cause MYH9-related disorder typically result in a nonfunctional version of the myosin-9 protein. The nonfunctional protein cannot properly interact with other subunits to form myosin IIA. Platelets and leukocytes, which only use myosin IIA, are most affected by a lack of functional myosin-9. It is thought that a lack of functional myosin IIA leads to the release of large, immature platelets in the bloodstream, resulting in a reduced amount of normal platelets. In leukocytes, the nonfunctional myosin-9 clumps together. These clumps of protein, called inclusion bodies, are a hallmark of MYH9-related disorder and are present in the leukocytes of everyone with this condition.

Related Gene(s)

Changes in this gene are associated with MYH9-related disorder.

  • MYH9

How do people inherit MYH9-related disorder?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. Approximately 30 percent of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of MYH9-related disorder?

These resources address the diagnosis or management of MYH9-related disorder and may include treatment providers.

  • Gene Review: MYH9-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK2689/)
  • Genetic Testing Registry: Epstein syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0398641)
  • Genetic Testing Registry: Fechtner syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0403445)
  • Genetic Testing Registry: Macrothrombocytopenia and progressive sensorineural deafness (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834478)
  • Genetic Testing Registry: May-Hegglin anomaly (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0340978)
  • Genetic Testing Registry: Sebastian syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1854520)
  • Lab Tests Online: Platelet Count (http://labtestsonline.org/understanding/analytes/platelet/tab/test)
  • MedlinePlus Encyclopedia: Glomerulonephritis (http://www.nlm.nih.gov/medlineplus/ency/article/000484.htm)
  • MedlinePlus Encyclopedia: Thrombocytopenia (http://www.nlm.nih.gov/medlineplus/ency/article/000586.htm)

You might also find information on the diagnosis or management of MYH9-related disorder in Educational resources (http://www.ghr.nlm.nih.gov/condition/myh9-related-disorder/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/myh9-related-disorder/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about MYH9-related disorder?

You may find the following resources about MYH9-related disorder helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Encyclopedia: Glomerulonephritis (http://www.nlm.nih.gov/medlineplus/ency/article/000484.htm)
    • Encyclopedia: Sensorineural Deafness (http://www.nlm.nih.gov/medlineplus/ency/article/003291.htm)
    • Encyclopedia: Thrombocytopenia (http://www.nlm.nih.gov/medlineplus/ency/article/000586.htm)
    • Health Topic: Cataract (http://www.nlm.nih.gov/medlineplus/cataract.html)
    • Health Topic: Hearing Disorders and Deafness (http://www.nlm.nih.gov/medlineplus/hearingdisordersanddeafness.html)
    • Health Topic: Kidney Diseases (http://www.nlm.nih.gov/medlineplus/kidneydiseases.html)
    • Health Topic: Platelet Disorders (http://www.nlm.nih.gov/medlineplus/plateletdisorders.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/180/resources/resources/1)

  • Additional NIH Resources - National Institutes of Health

    • National Eye Institute: Facts About Cataract (http://www.nei.nih.gov/health/cataract/cataract_facts.asp)
    • National Heart Lung and Blood Institute: What Is Thrombocytopenia? (http://www.nhlbi.nih.gov/health/health-topics/topics/thcp/)
    • National Kidney Disease Education Program (http://www.nkdep.nih.gov/)

  • Educational resources - Information pages

    • Boys Town National Research Hospital: Types of Hearing Loss (http://www.boystownhospital.org/knowledgeCenter/articles/hearing/Pages/TypesofHearing.aspx)
    • Centers for Disease Control and Prevention: Hearing Loss in Children (http://www.cdc.gov/ncbddd/hearingloss/index.html)
    • Children's Hospital Boston: Cataracts (http://www.childrenshospital.org/az/Site666/mainpageS666P0.html)
    • Children's Hospital Boston: Glomerulonephritis (http://www.childrenshospital.org/az/Site965/mainpageS965P0.html)
    • Children's Hospital Boston: Thrombocytopenia (http://www.childrenshospital.org/az/Site1740/mainpageS1740P0.html)
    • Cleveland Clinic: Thrombocytopenia (http://my.clevelandclinic.org/disorders/thrombocytopenia/hic_thrombocytopenia.aspx)
    • Johns Hopkins Heart and Vascular Institute: What are Platelets and Why are They Important? (http://www.hopkinsmedicine.org/heart_vascular_institute/clinical_services/centers_excellence/womens_cardiovascular_health_center/patient_information/health_topics/platelets.html)
    • Merck Manual Home Edition for Patients and Caregivers: Glomerulonephritis (http://www.merckmanuals.com/home/kidney_and_urinary_tract_disorders/kidney_filtering_disorders/glomerulonephritis_nephritic_syndrome.html)
    • Merck Manual Home Edition for Patients and Caregivers: Thrombocytopenia (http://www.merckmanuals.com/home/blood_disorders/bleeding_and_clotting_disorders/thrombocytopenia_itp_ttp.html)
    • Orphanet: Epstein Syndrome (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1019)
    • Orphanet: Fechtner Syndrome (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1984)
    • Orphanet: May-Hegglin Thrombocytopenia (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=850)
    • Orphanet: MYH9-Related Thrombocytopenia (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=182050)
    • Orphanet: Sebastian Syndrome (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=807)

  • Patient support - For patients and families

    • Family Village: Deaf/Hard of Hearing (http://www.familyvillage.wisc.edu/lib_deaf.htm)
    • National Kidney Foundation (http://www.kidney.org/)
    • National Organization for Rare Disorders (NORD): May Hegglin Anomaly (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/160/viewAbstract)
    • University of Kansas Medical Center Resource List: Hard of Hearing/Deafness (http://www.kumc.edu/gec/support/hearing.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK2689/)

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Epstein syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0398641)
    • Genetic Testing Registry: Fechtner syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0403445)
    • Genetic Testing Registry: Macrothrombocytopenia and progressive sensorineural deafness (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834478)
    • Genetic Testing Registry: May-Hegglin anomaly (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0340978)
    • Genetic Testing Registry: Sebastian syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1854520)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?term=%22MYH9-related%20disorder%22%20%5BDISEASE%5D%20OR%20%22MYH9-related%20macrothrombocytopenias%22%20%5BDISEASE%5D%20OR%20%22Epstein%20syndrome%22%20%5BDISEASE%5D%20OR%20%22Fechtner%20syndrome%22%20%5BDISEASE%5D%20OR%20%22May-Hegglin%20anomaly%22%20%5BDISEASE%5D%20OR%20%22Sebastian%20syndrome%22%20%5BDISEASE%5D%20OR%20NCT01133860%20%5BID-NUMBER%5D)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Thrombocytopenia%5BMAJR%5D)%20AND%20((myh9-related%20disorder%5BTIAB%5D)%20OR%20(MYH9%5BTIAB%5D)%20AND%20(thrombocytopenia%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)

  • OMIM - Genetic disorder catalog

    • EPSTEIN SYNDROME (http://omim.org/entry/153650)
    • FECHTNER SYNDROME (http://omim.org/entry/153640)
    • MACROTHROMBOCYTOPENIA AND PROGRESSIVE SENSORINEURAL DEAFNESS (http://omim.org/entry/600208)
    • MAY-HEGGLIN ANOMALY (http://omim.org/entry/155100)
    • SEBASTIAN SYNDROME (http://omim.org/entry/605249)

What other names do people use for MYH9-related disorder?

  • autosomal dominant MYH9 spectrum disorders
  • MYH9RD
  • MYH9-related macrothrombocytopenias

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about MYH9-related disorder?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding MYH9-related disorder?

autosomal ; autosomal dominant ; blood clotting ; capillaries ; cell ; cell division ; clotting ; cytokinesis ; cytoplasm ; end-stage renal disease ; ESRD ; gene ; incidence ; inclusion bodies ; kidney ; menstruation ; mutation ; myosin ; myosin II ; nucleus ; platelets ; protein ; renal ; renal disease ; sensorineural ; sensorineural hearing loss ; sign ; spectrum ; stage ; subunit ; syndrome ; thrombocytopenia ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Althaus K, Greinacher A. MYH9-related platelet disorders. Semin Thromb Hemost. 2009 Mar;35(2):189-203. doi: 10.1055/s-0029-1220327. Epub 2009 Apr 30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19408192?dopt=Abstract)
  • Gene Review: MYH9-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK2689/)
  • Kunishima S, Saito H. Advances in the understanding of MYH9 disorders. Curr Opin Hematol. 2010 Sep;17(5):405-10. doi: 10.1097/MOH.0b013e32833c069c. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20601875?dopt=Abstract)
  • Sekine T, Konno M, Sasaki S, Moritani S, Miura T, Wong WS, Nishio H, Nishiguchi T, Ohuchi MY, Tsuchiya S, Matsuyama T, Kanegane H, Ida K, Miura K, Harita Y, Hattori M, Horita S, Igarashi T, Saito H, Kunishima S. Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. Kidney Int. 2010 Jul;78(2):207-14. doi: 10.1038/ki.2010.21. Epub 2010 Mar 3. (http://www.ncbi.nlm.nih.gov/pubmed/20200500?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2011
Published: May 20, 2013