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Centronuclear myopathy is a condition that is characterized by muscle weakness (myopathy) in the skeletal muscles, which 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 droopy eyelids (ptosis) and weakness in the muscles that control eye movement (ophthalmoplegia). 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; the autosomal dominant type is more common than the autosomal recessive type.
Centronuclear myopathy can be caused by mutations in the DNM2 or BIN1 gene. 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. Mutations in other genes associated with this condition are found in a small percentage of cases. In some people with centronuclear myopathy, the cause of the disorder is unknown. Researchers are looking for additional genes that are associated with centronuclear myopathy.
Changes in these genes are associated with centronuclear myopathy.
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. Rarely, BIN1 gene mutations that are inherited in an autosomal dominant pattern can cause centronuclear myopathy.
Usually, BIN1 gene mutations that cause centronuclear myopathy are 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.
Other cases of centronuclear myopathy are typically inherited in an autosomal recessive manner, although some follow an autosomal dominant pattern.
These resources address the diagnosis or management of centronuclear myopathy and may include treatment providers.
You might also find information on the diagnosis or management of centronuclear myopathy in Educational resources and Patient support.
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
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You may find the following resources about centronuclear myopathy helpful. These materials are written for the general public.
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Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).
autosomal ; autosomal dominant ; autosomal recessive ; cardiomyopathy ; cell ; cell membrane ; cytoskeleton ; disability ; endocytosis ; gene ; inheritance ; inherited ; intracellular ; microtubule ; muscle cell ; muscle cells ; neuropathy ; nucleus ; ophthalmoplegia ; palate ; pattern of inheritance ; protein ; ptosis ; recessive ; scoliosis
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
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