nemaline myopathy 2

Muscle Weakness and Hypotonia

Nemaline myopathy 2, also known as nemaline myopathy, is a genetic disorder that affects the muscles. The primary signs and symptoms of this condition include:

• Severe muscle weakness: People with nemaline myopathy experience significant weakness in their muscles, particularly in the face, neck, and upper limbs.
• Hypotonia: Muscle tone is often reduced or absent, leading to a lack of strength and coordination.

Respiratory Difficulties

In some cases, nemaline myopathy can also affect the respiratory muscles, making it difficult for individuals to breathe properly. This can lead to:

• Feeding and swallowing difficulties: Infants with nemaline myopathy may struggle to feed or swallow due to weak facial and neck muscles.
• Respiratory problems: In severe cases, nemaline myopathy can cause respiratory failure, requiring immediate medical attention.

Other Symptoms

Additional symptoms associated with nemaline myopathy include:

• Foot deformities
• Abnormal curvature of the spine (scoliosis)
• Joint deformities (contractures)

It's essential to note that the severity and age of onset for nemaline myopathy can vary greatly from person to person. Some individuals may experience mild symptoms, while others may have more severe manifestations.

References:

• [1] Congenital Nemaline Myopathy: This is the most common form and is typically evident at birth. It manifests with severe muscle weakness and respiratory difficulties.
• [5] People with Nemaline myopathy have muscle weakness (myopathy) throughout the body, but it is typically most severe in the muscles of the face, neck, and limbs.
• [10] Nemaline myopathy 2 is an inherited skeletal muscle disorder that causes severe muscle weakness, hypotonia, and reduced or absent reflexes.

Diagnostic Tests for Nemaline Myopathy

Nemaline myopathy can be diagnosed through a combination of clinical evaluation, muscle biopsy, and molecular testing.

• Muscle Biopsy: A muscle biopsy is a surgical procedure that involves removing a small sample of muscle tissue. In the case of nemaline myopathy, a biopsy will show thread- or rod-like shapes (nemaline bodies) in the muscle tissue [1]. This can confirm a diagnosis of nemaline myopathy.
• Molecular Testing: Molecular testing can be used to identify genetic variants associated with nemaline myopathy. In families where the mutation is known, molecular testing may be available to confirm the diagnosis [4].
• Genetic Testing: Genetic testing can also be used to diagnose nemaline myopathy. This involves analyzing DNA samples from affected individuals and their family members to identify specific genetic variants associated with the condition [3].

Additional Diagnostic Tests

Other diagnostic tests that may be used in conjunction with muscle biopsy and molecular testing include:

• Imaging Studies: Imaging studies such as MRI or CT scans may be used to rule out other conditions that may cause similar symptoms.
• Electromyography (EMG): EMG is a test that measures the electrical activity of muscles. It can help diagnose muscle disorders, including nemaline myopathy.

References

[1] Context 1: A diagnosis of nemaline myopathy is suspected based upon a thorough clinical evaluation, a detailed patient and family history, identification of characteristic findings and molecular testing for genetic variants. [2] Context 5: Nemaline myopathy (NM) encompasses a large spectrum of myopathies characterized by hypotonia, weakness and depressed or absent deep tendon reflexes, with pathologic evidence of nemaline bodies (rods) on muscle biopsy. [3] Context 4: For this reason, the muscle sample must be considered along with the physical signs and/or molecular tests, in order for a diagnosis of nemaline myopathy to be made. [4] Context 6: Molecular testing can also be used to identify genetic variants associated with nemaline myopathy.

Current Status of Drug Treatment for Nemaline Myopathy

Nemaline myopathy, a congenital muscle disorder, currently lacks an effective drug treatment to halt its progression. However, research is ongoing to explore various therapeutic options.

• No specific therapy: As of now, there is no specific therapy available to treat muscle weakness in nemaline myopathy [6].
• Treatment possibilities: Researchers have identified potential treatment possibilities for each genotype and level of evidence, including drug targets and treatment options in development [5].
• Tirasemtiv and omecamtiv mecarbil: Studies have shown that tirasemtiv, a fast skeletal muscle activator, and omecamtiv mecarbil, a MYH7 activator, may improve force production of type I fibers, demonstrating therapeutic potential to treat nemaline myopathy [6][7].
• Chemotherapy-based approach: A chemotherapy-based approach is the preferred treatment for sporadic late-onset nemaline myopathy with a monoclonal protein [4][9].

Future Directions

While no effective drug treatment exists currently, research continues to explore new therapeutic options. Gene therapy clinical trials have shown promise in restoring expression of absent muscle proteins in patients with various congenital myopathies, including nemaline myopathy [13]. These findings suggest that targeted therapies may be developed to address the underlying causes of nemaline myopathy.

References

[4] Chemotherapy-based approach is the preferred treatment for sporadic late-onset nemaline myopathy with a monoclonal protein. Int J Cancer. 2021 Jun 1;148(11):2807-2814. [5] Keywords included but were not limited to ‘nemaline myopathy,’ ‘molecular therapy,’ ‘drug therapy,’ ‘gene therapy,’ ‘gene transcription,’ ‘exon skipping’ and ‘RNA splicing.’ [6] by JM de Winter · 2021 · Cited by 15 — To date, no specific therapy is available to treat muscle weakness in nemaline myopathy. [7] by AE Eşkazan · 2021 · Cited by 2 — Chemotherapy-based approach is the preferred treatment for sporadic late-onset nemaline myopathy with a monoclonal protein. Int J Cancer. 2021. [13] Again, despite lack of treatment, small gene therapy clinical trials performed in patients with several of these diseases show promise and suggest that expression of absent muscle proteins can be successfully and safely restored.

The differential diagnosis for nemaline myopathy (NM) is complex and includes several neuromuscular diseases that can display similar symptoms, such as:

• Myotonic dystrophy type 1: This condition can cause muscle weakness, wasting, and stiffness, which may be similar to NM.
• Congenital muscular dystrophy: This condition can also present with muscle weakness, hypotonia, and feeding difficulties, making it a differential diagnosis for NM.
• Prader–Willi syndrome: This genetic disorder can cause muscle weakness, hypotonia, and feeding problems, which may be similar to NM.
• Dermatomyositis: This condition can cause muscle weakness, skin rash, and other symptoms that may be similar to NM.
• Centronuclear myopathies: These conditions can also present with muscle weakness, bulbar weakness, and other symptoms that may be similar to NM.

According to [10], significant bulbar weakness leading to insufficient sucking and swallowing is a prominent feature in nemaline myopathy, MTM1-related myotubular myopathy, and the centronuclear myopathies associated with severe DNM2 and severe RYR1 mutations. The most important differential diagnoses are Prader–Willi syndrome, CMS, DM1, and severe SMA (type 0).

It's essential to exclude life-threatening causes before following a diagnostic algorithm and performing additional tests [11].