centronuclear myopathy 5

Centronuclear Myopathy-5 (CNM5): A Rare Congenital Muscle Disorder

Centronuclear Myopathy-5 (CNM5) is a rare autosomal recessive congenital myopathy characterized by severe neonatal hypotonia, respiratory insufficiency, and difficulty feeding. This condition is often present at birth and can be life-threatening.

Key Features:

• Severe neonatal hypotonia (weakness or floppiness of the muscles)
• Respiratory insufficiency (difficulty breathing)
• Difficulty feeding
• Some patients may die in infancy
• Others may develop dilated cardiomyopathy (a condition where the heart becomes enlarged and cannot pump blood effectively)

Delayed Motor Development:

Children with CNM5 often show severely delayed motor development, which means they may have difficulty crawling, walking, or performing other physical activities.

References:

• [1] Description. Centronuclear myopathy-5 (CNM5) is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Some patients die in infancy, and some develop dilated cardiomyopathy. Children show severely delayed motor development (summary by Agrawal et al., 2014).
• [2] Centronuclear myopathy-5 (CNM5) is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Some patients die in infancy, and some develop dilated cardiomyopathy. Children show severely delayed motor development (summary by Agrawal et al., 2014).
• [10] Centronuclear myopathy-5 (CNM5) is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Some patients die in infancy, and some develop dilated cardiomyopathy. Children show severely delayed motor development (summary by Agrawal et al., 2014). For a discussion of genetic heterogeneity of centronuclear ...

Common Signs and Symptoms of Centronuclear Myopathy

Centronuclear myopathy, a rare inherited neuromuscular condition, can manifest differently in various forms and individuals. Some common signs and symptoms include:

• Muscle weakness: Affecting the skeletal muscles used for movement.
• Hypotonia (lack of muscle tone): Characterized by decreased muscle strength and tone.
• Delayed motor milestones: Difficulty with physical development, such as walking or sitting up.
• Facial weakness: Weakness in the facial muscles, which can lead to droopy eyelids (ptosis).
• Extraocular muscle involvement: Affecting the muscles responsible for eye movement.

These symptoms can vary greatly among individuals and may worsen over time. In some cases, centronuclear myopathy can cause life-limiting symptoms, such as early respiratory failure.

References:

• [5] Some people with centronuclear myopathy do not have identified mutations in the DNM2, BIN1, or TTN genes.
• [6] Extraocular muscle involvement is also common in all forms. Other common signs and symptoms include delayed motor milestones, facial weakness and ptosis.
• [11] Centronuclear myopathy is a condition characterized by muscle weakness (myopathy) and wasting (atrophy) in the skeletal muscles, which are the muscles used for movement.

Centronuclear myopathy-5 (CNM5) is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Diagnostic tests for CNM5 are crucial in confirming the condition.

Typical Histopathological Findings

Diagnostic testing for CNM5 typically involves histopathological findings, which include:

• Increased frequency of central nuclei
• Type 1 fiber predominance and hypotrophy

These findings can be confirmed through muscle biopsy. [4][9]

Genetic Testing

Genetic testing is also available to confirm the diagnosis of CNM5. This involves analyzing the SPEG gene for deletion/duplication analysis. [14]

Other Diagnostic Tests

While not specific to CNM5, other diagnostic tests may be used in conjunction with histopathological findings and genetic testing to rule out other conditions. These include:

• Electromyography (EMG) and nerve conduction studies (NCS)
• Muscle magnetic resonance imaging (MRI)

These tests can help identify muscle weakness and wasting, which are characteristic of CNM5. [7][13]

Comprehensive Myopathy Panel

The Invitae Comprehensive Myopathy Panel analyzes genes associated with inherited myopathies, including those that may be related to CNM5. This panel can provide a comprehensive diagnosis for patients suspected of having CNM5 or other myopathic conditions. [5]

Current Status of Therapeutic Proof-of-Concept Studies for Congenital Myopathies

According to a review by C Gineste in 2023 [5], there is currently no approved therapy for any congenital myopathies, including centronuclear myopathy. However, the review aims to describe the current status of therapeutic proof-of-concept studies.

Unfortunately, these studies have not yet led to an effective treatment or cure for centronuclear myopathy. The management of symptoms remains a crucial aspect of care, with therapies aimed at alleviating discomfort and improving quality of life.

Key Points:

• No approved therapy exists for congenital myopathies [5]
• Therapeutic proof-of-concept studies have not led to an effective treatment or cure [5]
• Management of symptoms is essential, focusing on alleviating discomfort and improving quality of life

Citations: [5] by C Gineste · 2023 · Cited by 21

Differential Diagnosis of Centronuclear Myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous congenital myopathy characterized by muscle weakness, atrophy, and variable degrees of cardiorespiratory involvement. When considering the differential diagnosis for CNM, several other conditions should be taken into account.

• Congenital Myotonic Dystrophy: This condition presents with severe neonatal hypotonia and is a major differential diagnosis for CNM.
• Other Forms of Congenital Myopathies: These include various types of myopathies that can present with similar clinical features to CNM, such as muscle weakness and atrophy.
• Neuromuscular Conditions with Severe Neonatal Hypotonia: Other conditions, such as neuromuscular disorders, can also present with severe neonatal hypotonia and should be considered in the differential diagnosis for CNM.

Key Features to Consider

When attempting to differentiate CNM from other conditions, several key features should be taken into account:

• Muscle Pathology: The presence of centrally located nuclei on muscle biopsy is a characteristic feature of CNM.
• Clinical Examination: A thorough clinical examination can help identify the specific features of CNM and distinguish it from other conditions.
• Investigations: Various investigations, such as muscle imaging and genetic testing, can also aid in the differential diagnosis of CNM.

References

• [5] Centronuclear myopathy. Suggest an update ... The main differential diagnoses include other forms of congenital myopathies or other neuromuscular conditions with severe neonatal hypotonia.
• [12] Centronuclear myopathy (CNM) is a congenital myopathy with the characteristic morphology of centrally located nuclei in the vast majority of muscle fibers.