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MYH9-related disorders
These disorders typically affect blood platelet size and function, increasing the risk of bruising and bleeding. They can also impact hearing, kidneys, and eyes, affecting individuals from childhood onwards.
Overview
MYH9-related disorders are a group of rare, inherited conditions affecting several body systems, most notably the blood. They are caused by pathogenic variants in the MYH9 gene. A key feature is macrothrombocytopenia, meaning a reduced number of unusually large platelets in the blood [PMID:19363073]. Platelets are small blood cells crucial for clotting and stopping bleeding. In addition to blood-related issues, these disorders can also lead to problems with hearing, kidney function, and the eyes.
Symptoms & clinical features
The symptoms of MYH9-related disorders can vary significantly among individuals, even within the same family. Common symptoms related to platelet dysfunction include easy bruising, nosebleeds, heavy menstrual bleeding, and prolonged bleeding after injury or surgery [PMID:19363073]. These bleeding symptoms often appear early in life. Beyond bleeding, individuals may experience progressive high-frequency hearing loss, which can begin in childhood or adolescence. Kidney problems, such as protein in the urine (proteinuria) and kidney impairment, may develop later. Some individuals also develop cataracts or other eye abnormalities.
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Affected organs
MYH9-related disorders primarily affect the blood, specifically the platelets, leading to problems with blood clotting. The ears are frequently affected, with many individuals experiencing progressive hearing loss. The kidneys can also be impacted, potentially leading to kidney disease. Less commonly, the eyes may be affected, with conditions like cataracts observed in some individuals. The range of organs affected and the severity of symptoms can differ greatly.
Risks & severity
The severity of MYH9-related disorders varies, from mild bleeding tendencies to more significant complications. The risk of bleeding is often lifelong, though its impact can range. Hearing loss is typically progressive, meaning it worsens over time, and can start at various ages. Kidney complications, such as chronic kidney disease, may develop in adulthood and can sometimes be severe [PMID:16523919]. The exact prevalence of MYH9-related disorders is not well established due to their rarity and the variable presentation of symptoms.
Genetic causes
MYH9-related disorders are caused by pathogenic variants in the MYH9 gene. This gene provides instructions for making a protein called non-muscle myosin heavy chain IIA (NMMHC-IIA). This protein is essential for various cellular functions, including cell movement, division, and maintaining cell structure. In blood cells like platelets, NMMHC-IIA plays a crucial role in their formation and function. Pathogenic variants in MYH9 lead to an abnormal NMMHC-IIA protein, which disrupts these vital cellular processes, resulting in the characteristic features of the disorder, such as abnormally large platelets and their impaired function [PMID:19363073].
- MYH9 myosin heavy chain 9
Inheritance pattern
MYH9-related disorders are inherited in an autosomal dominant pattern. This means that a person only needs one copy of the altered MYH9 gene in each cell to develop the condition. Typically, an affected individual inherits the altered gene from one parent who also has the condition. In some cases, the genetic variant can occur spontaneously in the affected individual, meaning neither parent carries the variant. Each child of an affected parent has a 50% chance of inheriting the altered gene and therefore developing the disorder.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of MYH9-related disorders often begins with the observation of macrothrombocytopenia (large platelets and reduced platelet count) in a routine blood test. If clinical features like bleeding, hearing loss, or kidney problems are also present, a referral to a clinical geneticist or haematologist may be made. The diagnosis is confirmed through genetic testing, which looks for pathogenic variants in the MYH9 gene. In the UK, genetic testing for these conditions is available through the NHS Genomic Medicine Service (GMS). The relevant R-code for testing for inherited thrombocytopenias, which includes MYH9-related disorders, would be initiated by a specialist clinician.
Management & lifestyle
Management for MYH9-related disorders focuses on addressing the specific symptoms experienced by the individual. For bleeding issues, management may involve avoiding certain medications that thin the blood, and in some cases, treatments to improve clotting during surgery or severe bleeding episodes. Regular monitoring of hearing is important, and hearing aids or other interventions may be considered for progressive hearing loss. Kidney function is typically monitored regularly, and management may include medications to protect kidney function or, in severe cases, dialysis or kidney transplantation. Management plans are always individualised and coordinated by a team of specialists within the NHS.
UK care pathway
In the UK, individuals suspected of having an MYH9-related disorder would typically be referred by their GP to a relevant specialist, such as a haematologist, nephrologist, or clinical geneticist. If a genetic condition is suspected, the individual would be referred to the NHS Genomic Medicine Service (GMS) for genetic counselling and testing. Genetic counsellors provide information, support, and help families understand the inheritance patterns and implications of a diagnosis. The GMS uses specific R-codes for genetic tests, ensuring that the appropriate investigations are carried out.
Frequently asked questions
What does 'macrothrombocytopenia' mean?
Macrothrombocytopenia refers to a condition where a person has a reduced number of blood platelets (thrombocytopenia), and these platelets are unusually large in size (macro-). This is a common feature of MYH9-related disorders.
If I have an MYH9-related disorder, will my children inherit it?
As MYH9-related disorders are inherited in an autosomal dominant pattern, if you have the condition, there is a 50% chance with each pregnancy that your child will inherit the altered gene and therefore the disorder.
Can the symptoms of MYH9-related disorders change over time?
Yes, symptoms can change over time. For example, hearing loss is often progressive, meaning it can worsen. Kidney problems may also develop or become more severe with age. Regular monitoring is important to manage these changes.
Is there a cure for MYH9-related disorders?
Currently, there is no cure for MYH9-related disorders. Treatment focuses on managing the specific symptoms an individual experiences, such as addressing bleeding issues, managing hearing loss, and monitoring kidney function to maintain overall health.
What kind of doctors will be involved in my care?
Your care will likely involve a team of specialists, depending on your symptoms. This may include a haematologist (blood specialist), an audiologist (hearing specialist), a nephrologist (kidney specialist), and a clinical geneticist for overall coordination and genetic counselling.
References
- Althaus K, Greinacher A. MYH9-related platelet disorders. Seminars in thrombosis and hemostasis. 2009. PMID: 19408192
- Singh N, Nainani N, Arora P. CKD in MYH9-related disorders. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2009. PMID: 19726116
- Tabibzadeh N, Fleury D, Labatut D. MYH9-related disorders display heterogeneous kidney involvement and outcome. Clinical kidney journal. 2019. PMID: 31384440
- Runkle JR, Penney SW. May-Hegglin Anomaly. 2026. PMID: 28722981
- Chen Z, Shivdasani RA. Regulation of platelet biogenesis: insights from the May-Hegglin anomaly and other MYH9-related disorders. Journal of thrombosis and haemostasis : JTH. 2009. PMID: 19630815
- Vassallo D, Erekosima I, Kanigicherla D. Myosin heavy chain-9-related disorders (MYH9-RD): a case report. Clinical kidney journal. 2013. PMID: 26015866
- Saposnik B, Binard S, Fenneteau O. Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-Related Disorders. Molecular genetics & genomic medicine. 2014. PMID: 25077172
- Kashtan CE, Segal Y. Genetic disorders of glomerular basement membranes. Nephron. Clinical practice. 2011. PMID: 21071975