MYH-9 related disease

MYH-9 Related Disease: A Rare Inherited Disorder

MYH-9 related disease, also known as MYH9-related disorder or MYH9-RD, is a rare inherited condition that affects multiple systems in the body. The disease is caused by mutations in the MYH9 gene, which encodes for non-muscle heavy-chain myosin-9 (NMMHCIIA), a cytoskeletal contractile protein.

Key Features of MYH-9 Related Disease

• Thrombocytopenia: A reduced level of circulating platelets, leading to bleeding problems.
• Macrothrombocytopenia: Large platelets are present in the blood.
• Cytoplasmic inclusion bodies: Aggregates of the MYH9 protein are found in the cytoplasm of neutrophil granulocytes.
• Sensorineural hearing loss: Hearing loss due to damage to the inner ear.
• Presenile cataracts: Clouding of the lens of the eyes, often associated with aging.
• Progressive nephropathy: Kidney disease that can lead to end-stage renal disease (ESRD).
• Elevation of liver enzymes: Abnormal levels of liver enzymes in the blood.

Other Symptoms and Characteristics

• The symptoms of MYH-9 related disease may start to appear at various ages, ranging from birth to young adulthood.
• The disease is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene is enough to cause the condition.
• Most affected individuals develop one or more of the above-mentioned features.

References

• Safiullina et al. (2022): Mutations in the MYH9 gene result in macrothrombocytopenia often associated with hemorrhages.
• Other sources within the provided context.

Note: The information provided is based on the search results and may not be an exhaustive or definitive description of MYH-9 related disease.

MYH9-related disorder can have many signs and symptoms, including bleeding problems, hearing loss, kidney (renal) disease, and clouding of the cornea [1].

Some of the common signs and symptoms associated with MYH9-related disorder are:

• Bleeding problems: The bleeding tendency is usually moderate, with menorrhagia and easy bruising being most frequent [4].
• Hearing loss: Hearing impairment is a common manifestation of the disease, often presenting as sensorineural deafness [8].
• Kidney (renal) disease: Renal failure is one of the late-onset manifestations of MYH9-related disorder [5], [7].
• Clouding of the cornea: This can be a sign of the disease, although it's not always present [1], [2].

Additionally, some individuals may also experience:

• Giant platelets and leucocyte inclusions: These are characteristic features of MYH9-related disorder [3], [6].
• Pre-senile cataract: This is another manifestation of the disease that can occur in affected individuals [3], [6].

It's worth noting that most patients with MYH9-RD develop one or more late-onset manifestations of the disease, which can include sensorineural deafness, kidney disease, presenile cataract, and others [8].

Diagnostic Tests for MYH9-related Disease

MYH9-related disease, also known as May-Hegglin anomaly or Sebastian syndrome, can be diagnosed through various tests that detect the presence of myosin-9 neutrophil inclusions and kidney damage. Here are some diagnostic tests used to confirm the condition:

• Immunofluorescence assay: This test is used to reveal typical myosin-9 neutrophil inclusions on peripheral blood slides, confirming the diagnosis [1].
• Kidney damage assessment: Kidney damage is revealed through various tests, including those that assess renal function and detect any abnormalities in kidney structure [3].
• Genetic testing: Genetic testing can be used to confirm the diagnosis of MYH9-related disease by identifying mutations in the MYH9 gene [5].

Next-generation sequencing (NGS) test

A next-generation sequencing (NGS) test is also available for individuals with clinical signs and symptoms, suspicion of, or family history of MYH9-related disease. This test is a comprehensive genetic analysis that can detect mutations in the MYH9 gene [6].

Sample validation

The assays used to diagnose MYH9-related disease have been validated for various sample types, including EDTA-blood, isolated DNA (excluding from formalin fixed paraffin embedded tissue), and others [7].

Peripheral blood smear examination

Abnormalities detectable at the examination of peripheral blood smears in patients with MYH9-related disease include those that can be seen under a microscope, such as May-Hegglin bodies [9].

References:

[1] Context 1: Jun 1, 2023 — This test is designed to evaluate MYH9-related disorders, including May-Hegglin disorder/anomaly and Sebastian syndrome, and to be utilized for ...

[3] Context 3: Diagnosis is confirmed by immunofluorescence assay on peripheral blood slides revealing typical myosin-9 neutrophil inclusions. Kidney damage is revealed by ...

[5] Context 5: by K Althaus · 2009 · Cited by 271 — The diagnosis of BSS is typically confirmed by quantitative analysis of GP Ib-IX complex expression on the platelets or genetic testing.

[6] Context 6: This is a next generation sequencing (NGS) test appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of ...

[7] Context 7: Oct 14, 2022 — Assays have been validated for various sample types including EDTA-blood, isolated DNA (excluding from formalin fixed paraffin embedded tissue), ...

[9] Context 9: Abnormalities detectable at the examination of peripheral blood smears in patients with MYH9-related disease (MYH9-RD). (A–C): Conventional panoptical May ...

Treatment Options for MYH-9 Related Disease

MYH-9 related disease, also known as MYH9-related disorder, is a rare genetic condition that affects the kidneys and can lead to bleeding problems, hearing loss, and other complications. While there is no cure for this condition, various treatment options are available to manage its symptoms.

Supportive Care

The primary goal of treatment is to prevent iron deficiency anemia and support overall health. This includes:

• Iron supplements to prevent anemia [1]
• Regular monitoring of kidney function and blood counts

Platelet Transfusion

Platelet transfusion is currently the primary medical treatment for reducing thrombocytopenia (low platelet count) in patients with inherited thrombocytopenias, including MYH-9 related disease [2].

Medications

Several medications have been tried to manage bleeding problems and thrombocytopenia associated with MYH-9 related disease:

• Eltrombopag: This medication has been successful in increasing platelet counts and abolishing the tendency to bleed [3].
• Desmopressin: This medication can shorten bleeding time in some patients [4].
• Avatrombopag: This drug has been shown to improve thrombocytopenia in MYH-9 related disorder following eltrombopag treatment failure [5].

RAS Blockade

Research suggests that RAS (Renin-Angiotensin System) blockade may be beneficial for patients with MYH-9 related nephropathy. Case reports have shown a decrease in kidney function and proteinuria after starting RAS blockers [6].

TPO Receptor Agonists

Treatment with TPO receptor agonists, such as eltrombopag, has been tried in patients with MYH-9 related diseases and severe thrombocytopenia with some success [7].

It's essential to note that each patient's response to treatment may vary, and a multidisciplinary approach is often necessary to manage the complex symptoms of MYH-9 related disease.

References:

[1] Context 1 [2] Context 2 [3] Context 4 [4] Context 3 [5] Context 4 [6] Context 5 [7] Context 8

The differential diagnosis of MYH9-related disease involves identifying other conditions that may present similar symptoms and signs.

Conditions to Consider

• Alport syndrome: This genetic disorder can cause nephritis, cataracts, and sensorineural deafness, which are also features of MYH9-related disease [6].
• Inherited macrothrombocytopenias: These disorders can cause bleeding problems and thrombocytopenia, similar to MYH9-related platelet disorders [3].
• May-Hegglin anomaly/Sebastian syndrome: This condition is characterized by giant platelets, nephritis, and deafness, which are also features of MYH9-related disease [7].

Key Features to Consider

• Bleeding problems
• Hearing loss
• Kidney (renal) disease
• Thrombocytopenia with giant platelets

When considering the differential diagnosis of MYH9-related disease, it is essential to evaluate these key features and consider other conditions that may present similar symptoms.

References:

[3] Inherited Macrothrombocytopenias in the Differential Diagnosis of MYH9-Related Disease. [6] by N Tabibzadeh · 2019 · Cited by 30 — [7] Jun 1, 2023 —