Centronuclear myopathy

A group of rare congenital myopathies

Centronuclear myopathy (CNM) is a group of rare congenital myopathies characterized by muscle weakness and distinctive histological features, notably the presence of centrally located nuclei in muscle fibers. These myopathies are genetically heterogeneous and can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.

Classification

Centronuclear myopathy is classified based on the mode of inheritance and the specific genetic mutations involved. The main types include:

• X-linked centronuclear myopathy: Caused by mutations in the MTM1 gene, this form is also known as myotubular myopathy. It primarily affects males and is the most severe form, often presenting in infancy.

• Autosomal dominant centronuclear myopathy: Often associated with mutations in the DNM2 gene, this form can present at any age and varies in severity.

• Autosomal recessive centronuclear myopathy: This form can be caused by mutations in several genes, including BIN1, RYR1, and TTN. It typically presents in childhood or adolescence.

Pathophysiology

The hallmark of centronuclear myopathy is the abnormal positioning of nuclei in the center of muscle fibers, rather than at the periphery. This is thought to result from defects in muscle cell development and maintenance. The specific pathophysiological mechanisms vary depending on the genetic mutation involved. For example, mutations in the MTM1 gene affect the protein myotubularin, which is involved in phosphoinositide metabolism, while DNM2 mutations affect dynamin 2, a protein involved in endocytosis and membrane trafficking.

Clinical Features

The clinical presentation of centronuclear myopathy can vary widely depending on the type and severity of the condition. Common features include:

• Muscle weakness, particularly in the proximal muscles
• Hypotonia (reduced muscle tone)
• Delayed motor milestones
• Respiratory difficulties, especially in severe cases
• Facial muscle weakness, leading to a characteristic facial appearance

Diagnosis

Diagnosis of centronuclear myopathy typically involves a combination of clinical evaluation, muscle biopsy, and genetic testing. Muscle biopsy reveals the characteristic central nuclei in muscle fibers. Genetic testing can identify specific mutations responsible for the condition.

Management

There is currently no cure for centronuclear myopathy, and management focuses on supportive care to improve quality of life. This may include:

• Physical therapy to maintain muscle strength and flexibility
• Respiratory support, such as non-invasive ventilation
• Orthopedic interventions to address skeletal deformities
• Nutritional support to ensure adequate caloric intake

Prognosis

The prognosis for individuals with centronuclear myopathy varies widely depending on the type and severity of the condition. X-linked myotubular myopathy often has a poor prognosis due to severe respiratory involvement, while other forms may have a more favorable outcome with appropriate management.

Related pages

• Congenital myopathy
• Muscle biopsy
• Genetic testing
• Respiratory support