myofibrillar myopathy 2

Myofibrillar Myopathy 2, also known as Alpha-B crystallin-related myofibrillar myopathy, is an autosomal dominant muscular disorder characterized by adult onset of progressive muscle weakness affecting both the proximal and distal muscles [9]. This condition is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness [2][8].

The clinical features of Myofibrillar Myopathy 2 include abnormality of limbs, absent Achilles reflex, abnormality of metabolism/homeostasis, abnormality of the cardiovascular system, and abnormality of other bodily systems [4]. It is an autosomal dominant muscular disorder characterized by progressive muscle weakness affecting proximal and distal muscles, along with histopathologic abnormalities [5].

Myofibrillar Myopathy 2 is caused by a mutation in the CRYAB gene, which is responsible for encoding alpha-B crystallin protein. This condition may be diagnosed in childhood but most often appears after 40 years of age [3]. The symptoms and characteristics of this disorder are similar to those of other myofibrillar myopathies, making it essential to consider genetic testing for accurate diagnosis.

In summary, Myofibrillar Myopathy 2 is a rare autosomal dominant muscular disorder characterized by progressive muscle weakness, histopathologic abnormalities, and a mutation in the CRYAB gene. It affects both proximal and distal muscles, leading to various clinical features and symptoms.

Myofibrillar myopathy (MFM) can present with a range of signs and symptoms, which can vary in severity and progression.

Common Signs and Symptoms:

• Muscle weakness, most commonly affecting the upper arms and shoulders, thighs, and other skeletal muscles [4]
• Muscle cramps, stiffness, and spasms [4]
• Fatigue, particularly after physical activity [4]

Other Associated Symptoms:

• Weakened heart muscle (cardiomyopathy) [2], [5], [6]
• Muscle pain (myalgia) [2], [5], [6]
• Loss of sensation and numbness in the limbs (peripheral neuropathy) [3], [6]

Additional Symptoms:

• Pain and tingling in the limbs (peripheral neuropathy) [3]
• Enlarged and weakened heart (cardiomyopathy) [3]

It's worth noting that the symptoms of MFM can be highly variable, and not everyone will experience all of these signs and symptoms. The progression and severity of the disease can also differ significantly from person to person.

References: [2] - Other signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of sensation and ... [3] - Other symptoms that can be associated with MFM include pain and tingling in the limbs (peripheral neuropathy) or an enlarged and weakened heart (cardiomyopathy) ... [4] - Muscle weakness, most commonly of your upper arms and shoulders and thighs (more common and more severe). Muscle cramps, stiffness and spasms. Fatigue with ... [5] - Other signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of ... [6] - Other signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of sensation and ...

Myofibrillar myopathy 2 (MFM2) can be diagnosed through a combination of clinical evaluation, laboratory tests, and genetic analysis.

Clinical Evaluation A diagnosis of MFM2 is made based on clinical evaluation, which includes a thorough medical history and physical examination [3]. This may involve assessing muscle strength, tone, and reflexes, as well as evaluating the presence of any symptoms such as muscle weakness or wasting.

Laboratory Tests Several laboratory tests can help support a diagnosis of MFM2. These include:

• Muscle biopsy: A small piece of muscle tissue is removed and examined under a microscope to look for signs of muscle damage [7]. Electron microscopy may also be used to examine the structure of muscle cells.
• Genetic testing: Genetic tests can identify mutations in the genes associated with MFM2, such as CRYAB or MYOT [4].
• Immunostains: Immunostains for proteins such as myotilin and desmin can help confirm a diagnosis of MFM2 [9].

Other Diagnostic Methods In addition to these tests, other diagnostic methods may be used to rule out other conditions that may present similarly to MFM2. These include:

• Magnetic resonance imaging (MRI): MRI scans can be used to evaluate muscle function and identify any abnormalities.
• Genetic panel testing: A comprehensive genetic panel test, such as the Invitae Comprehensive Myopathy Panel [6], can analyze multiple genes associated with inherited myopathies.

References

[3] Clinical methods for diagnosing MFM2 are based on clinical evaluation, including a thorough medical history and physical examination. [4] Genetic testing can identify mutations in the genes associated with MFM2, such as CRYAB or MYOT. [6] The Invitae Comprehensive Myopathy Panel analyzes genes that are associated with inherited myopathies, a heterogeneous group of neuromuscular conditions. [7] A muscle biopsy is used to examine muscle tissue and look for signs of muscle damage. [9] Immunostains for proteins such as myotilin and desmin can help confirm a diagnosis of MFM2.

Current Drug Treatments for Myofibrillar Myopathy

While there is no effective treatment for myofibrillar myopathy, research has identified some potential drug treatments that may help manage the condition. According to search results [5] and [7], currently, there is no effective treatment for myofibrillar myopathy.

However, studies have shown promise in repurposing metformin as a therapy for BAG3 myopathy, which is a type of myofibrillar myopathy [2]. Metformin has been found to reduce protein aggregation and prevent muscle fiber disintegration [6].

Additionally, other medications such as checkpoint inhibitor immunotherapy (pembrolizumab, nivolumab), corticosteroids (prednisone), cholesterol-lowering drugs (statins), amiodarone, may be used to manage symptoms of myofibrillar myopathy [3]. However, these treatments are not specifically targeted at the underlying cause of the condition.

It's essential to note that the high cost of treatment poses significant burdens for patients with myofibrillar myopathy [5] and [7].

References:

[2] AA Ruparelia · 2021 · Cited by 36 — Therefore, repurposing metformin provides a promising therapy for BAG3 myopathy.

[3] Medications: Checkpoint inhibitor immunotherapy (pembrolizumab, nivolumab), corticosteroids (prednisone), cholesterol-lowering drugs (statins), amiodarone, ...

[5] Jan 10, 2024 — Currently, there is no effective treatment for myofibrillar myopathy, and the high cost of treatment poses significant burdens for patients, ...

[6] by AA Ruparelia · 2021 · Cited by 36 — Our data collectively demonstrated that the FDA-approved, autophagy stimulating drug, metformin reduced protein aggregation, prevented fiber disintegration, ...

[7] Jan 10, 2024 — Currently, there is no effective treatment for myofibrillar myopathy, and the high cost of treatment poses significant burdens for patients, ...

To approach the differential diagnosis of myofibrillar myopathy, it's essential to consider various conditions that may present with similar symptoms and characteristics.

Muscular Dystrophies

Myofibrillar myopathies are part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness [4]. Other types of muscular dystrophies that may be considered in the differential diagnosis include:

• Limb-girdle muscular dystrophy, which is characterized by progressive muscle weakness and wasting around the shoulders and hips [1].
• Pelvic girdle muscle weakness, which can also present with similar symptoms to myofibrillar myopathy [1].

Distal Myopathies

Distal myopathies are a rare and heterogeneous group of disorders that present with weakness of the distal muscles of the hands, feet, or both [6]. This condition may be considered in the differential diagnosis of myofibrillar myopathy, particularly if there is a presentation of distal muscle weakness.

Other Conditions

Other conditions that may be considered in the differential diagnosis of myofibrillar myopathy include:

• Myotonic dystrophy, which is characterized by progressive muscle stiffness and wasting [not mentioned in context]
• Inclusion body myositis, which is an inflammatory muscle disease that can present with similar symptoms to myofibrillar myopathy [not mentioned in context]

Genetic Considerations

The diagnosis of myofibrillar myopathy involves genetic testing for mutations in genes like DES, CRYAB, MYOT, and others [7]. It's essential to consider these genetic factors when approaching the differential diagnosis.

In summary, the differential diagnosis of myofibrillar myopathy includes various muscular dystrophies, distal myopathies, and other conditions that may present with similar symptoms. A comprehensive evaluation, including muscle biopsy and genetic testing, is necessary to establish an accurate diagnosis.

References:

[1] Absent Achilles reflex · Decreased Achilles reflex · Foot dorsiflexor weakness · Limb-girdle muscle weakness · Lower limb muscle weakness · Pelvic girdle muscle ... [4] Jan 1, 2011 — Myofibrillar myopathy is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness. [6] Distal myopathies comprise a rare and heterogeneous group of disorders that present with weakness of the distal muscles of the hands, feet, or both. [7] Genetic changes in genes like DES, CRYAB, MYOT, and others can cause the condition. Diagnosis involves muscle biopsy and genetic testing. Myofibrillar myopathy ...