MYH9-Related Disorder - An Overview

Introduction

The MYH9-related disorder is a condition described by a physician in the 1900s. It is a bleeding condition that can be characterized by features that can be present at the time of birth, such as alteration in the blood cell levels and aggregation of the protein MYH9. Along with the bleeding manifestations, they can also develop problems related to hearing, kidneys, vision, and liver health. This article describes various symptoms of MYH9-related disorder and elaborates on treatment for the same.

What Is an MYH9-Related Disorder?

MYH9 disorder is a platelet bleeding disorder that can be detected in childhood or old age. It is distinguished by certain clinical conditions such as Epstein syndrome (a genetic condition occurring due to MYH9 gene mutation), Sebastian syndrome (a condition characterized by macro thrombocytopenia with nephritis - inflammation of kidney tissues and hearing loss), Hegglin anomaly (genetic disorder due to mutation in the MYH9 gene characterized by large platelets and thrombocytopenia) and Fechtner syndrome( a genetic condition associated with nephropathy, hearing loss, and vision loss). As all the conditions show a common genetic basis, they are categorized into one condition, which is termed a MYH9-related disorder. Commonly, it leads to cataract kidney and hearing issues.

What Are the Causes of MYH9-Related Disorders?

The MYH9-related disorder is an autosomal dominant disorder. It occurs due to a mutation of a gene responsible for making myosin 9 protein.

What Are the Signs and Symptoms of MYH9-Related Disorder?

The MYH9-related disorder can lead to the following symptoms:

• Nose bleeding, bleeding gums, easy bruising, menorrhagia (prolonged menstrual bleeding), bleeding after delivery, and continuous bleeding after a dental treatment or surgery.

• Gastrointestinal bleeding.

• Loss of hearing.

• End-stage kidney failure.

• Vision loss.

What Is the Diagnosis of MYH9-Related Disorder?

• This condition can be diagnosed by laboratory tests that show thrombocytopenia (decreased platelet levels) and enlarged platelets.

• Clumps of inclusion bodies present in leukocytes (white blood cells) can also be observed.

• Clinical symptoms also suggest the presence of an MYH9-related disorder.

Confirmation of the diagnosis can be done with the help of molecular genetic testing that includes single genomic testing and comprehensive gene testing.

What Is the Treatment Plan For MYH9-Related Disorder?

Hematologists and an expert in treating bleeding disorders should be consulted for a proper treatment plan. Treatment is the same as that of other bleeding disorders. The severity of the clinical conditions should also be considered when formulating a treatment plan. Generally, it is treated by avoiding medications that stop platelet function, such as Aspirin and necessary site compressions at the regions of injury. Antifibrinolytics, for example, Tranexamic acid, can be advised. In certain cases, platelet transfusion is also required before surgery.

Certain evaluations should be done after the initial diagnosis, as listed below, to elaborate the treatment plan.

• Microscopic evaluation of the platelet levels.

• Assessment of previous bleeding history and bleeding episodes.

• Complete blood count evaluation to detect anemia.

• Audiogram to rule out hearing loss and deafness.

• Urine analysis to determine the levels of creatinine.

• Evaluation of the eyes.

• Measurement of liver enzymes.

Treatment of Clinical Manifestations:

• Management is a multi-disciplinary approach.

Treatment of Bleeding Tendency and Thrombocytopenia:

• Transfusion of platelets can improve the count of platelets in the short term and help prevent bleeding episodes. It should be noted that the individuals are exposed to certain reactions and transmission of infections due to subsequent transfusion of platelets. The usage of antifibrinolytics can help in recovering from thrombocytopenia. Mild to moderate bleeding can be treated with Tranexamic acid. They can also be used as prophylaxis to cover hemostatic challenges. Thrombocytopenia is a condition that cannot be prevented. The individual must be aware of the medication that affects the functioning of platelets.
• Menorrhagia can be controlled or prevented using oral contraceptives.
• Gum bleeding can be controlled by following regular dental care.

Treatment of Hearing Loss:

• Cochlear implantation and hearing aids are necessary to improve hearing potential.
• Cochlear implantation can help in restore the sharing function in most cases suffering from severe deafness.
• An audiologist or otolaryngologist should devise the proper treatment.
• It is necessary to provide the individual with the necessary education regarding the damaging drugs to prevent the worsening of deafness.

Treatment for Kidney Failure:

• Medications to improve kidney health are advised, such as angiotensin-converting enzyme inhibitors.
• Dialysis or kidney transplantation may also be necessary.
• The nephrologist should advise all the treatments.

Treatment for Vision Loss:

• Cataract surgery, which can be done on an outpatient basis, can be opted for under the advice of an ophthalmologist.

Treatment of abnormal liver enzymes:

• There is no specific treatment.

Surveillance of the Treatment:

Annual assessment of laboratory reports related to bleeding and other hemostatic challenges should be monitored.

• Assessment every three years is necessary in case the patient reports worsening deafness.

• An assessment should be done every six months in individuals with a high risk of kidney damage.

• Cataract surgery should be evaluated every three years.

• Levels of liver enzymes depend on alteration in the severity.

What Are the Agents to Avoid in MYH9 Disorder?

• Drugs inhibiting the platelet function are administered in case of a bleeding tendency. Contact sports are avoided because there is a high risk of bruises or trauma.

• Alteration in liver enzyme levels and hepatotoxic drugs are used with caution.

• As Glucocorticoids can predispose to cataract development, they can be avoided.

What Is Genetic Counseling?

Genetic counseling is the process of providing the patient and their family members with education on the mode of inheritance, the acquisition of genetic disorders, and the nature of the disorder that helps in making medical decisions or personal decisions. It helps in assessing the risk of the disorder to the family members. The chance of the sibling of an individual with the disorder acquiring it is 50 percent, which can be determined by genetic counseling.

The status of the parents of individuals suffering from this condition determines the risk of MYH9 disorder to other family members.

Genetic counseling can also help in family planning when there is a high risk of transferring the disorder to the offspring.

Conclusion

MYH9 disorder occurs due to gene mutations inherited from parents. It needs a multi-disciplinary approach by specialists that include hematologists, nephrologists, ophthalmologists, and otolaryngologists. However, an efficient diagnosis forms the base for the best treatment outcome.