Centronuclear myopathy

Centronuclear myopathy is a condition that primarily affects skeletal muscles, which are the muscles that are used for movement. Researchers have described two forms of centronuclear myopathy, which are differentiated by their pattern of inheritance: autosomal dominant and autosomal recessive.

People with autosomal dominant centronuclear myopathy typically have normal early development. However, muscle weakness usually becomes evident during adolescence or early adulthood. The first symptoms are usually muscle pain during exercise and difficulty walking. Muscle weakness progressively worsens, and some people with this condition require wheelchair assistance in mid- to late adulthood. People with this condition may have weakness in the muscles that control eye movement (ophthalmoplegia) and droopy eyelids (ptosis). Rarely, affected individuals have disturbances in nerve function (neuropathy) or intellectual disability. Some people with autosomal dominant centronuclear myopathy are more severely affected and experience muscle weakness in infancy. These individuals walk at a later age than their peers, and they typically need wheelchair assistance in childhood or adolescence.

Autosomal recessive centronuclear myopathy is also characterized by progressive muscle weakness, which is usually apparent at birth or begins in childhood. People with this condition may also have foot abnormalities, a high arch in the roof of the mouth (high-arched palate), and abnormal side-to-side curvature of the spine (scoliosis). Some people experience mild to severe breathing problems related to the weakness of muscles needed for breathing. Rarely, the heart muscle is weakened (cardiomyopathy). Affected individuals frequently have ptosis, but ophthalmoplegia is less common.

Centronuclear myopathy is a rare condition; fewer than 50 affected families have been reported in the scientific literature. The autosomal dominant type is more common than the autosomal recessive type.

Centronuclear myopathy is caused by mutations in the DNM2 and BIN1 genes.

The DNM2 gene provides instructions for making a protein called dynamin 2. This protein is involved in endocytosis, a process that brings substances into the cell. Dynamin 2 also associates with tube-like structures called microtubules, which are part of a cell's structural framework (cytoskeleton). The BIN1 gene provides instructions for making a protein that interacts with other proteins (including dynamin 2) and is likely involved in cell membrane structure.

Normally, the nucleus is found at the edges of rod-shaped muscle cells. However, in people with centronuclear myopathy, the nucleus is located in the center of these cells. How this change in location of the nucleus affects muscle cell function is unknown. It is not well understood how mutations in the DNM2 or BIN1 genes lead to muscle weakness and the other specific features of centronuclear myopathy. Mutations in the DNM2 or BIN1 genes probably disrupt the transport of molecules within muscle cells (intracellular trafficking). DNM2 gene mutations may also impair microtubule association, while BIN1 gene mutations lead to abnormal muscle fiber structure.

Some people with centronuclear myopathy do not have identified mutations in the DNM2 or BIN1 genes. In these affected individuals, the cause of the condition is unknown.

Read more about the BIN1 and DNM2 genes.

When centronuclear myopathy is caused by mutations in the DNM2 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered DNM2 gene in each cell is sufficient to cause the disorder.

When this condition is caused by mutations in the BIN1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the BIN1 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.