Congenital Myopathies

Centronuclear myopathies, including myotubular myopathy

The centronuclear myopathies are named for the mislocation of cell nuclei in the muscle fibers. Normally, these nuclei are arranged around the periphery of the fiber. In these disorders, many of them are centrally located instead.

What is myotubular myopathy?

Myotubular myopathy is the most common and severe form of centronuclear myopathy, a type of inherited myopathy that causes problems with the tone and contraction of skeletal muscles.

What are the symptoms of myotubular myopathy?

Myotubular myopathy causes muscle weakness and hypotonia (lack of muscle tone) noticeable at birth. The weakness and hypotonia interfere with posture and movement, and can cause life-threatening difficulties with feeding and respiration. Sometimes, failure or infection of the lungs causes death in early infancy, but other infants with this disease survive into childhood. Usually, these children require a feeding tube and assisted ventilation.

Contractures (joints frozen in place because of muscle weakness) may develop, particularly in the hips and knees. Spinal curvature (scoliosis) also may develop in childhood.

What causes myotubular myopathy?

This disease is caused by defects or deficiencies of myotubularin, a protein thought to promote normal muscle development. It is inherited in an X-linked recessive pattern, meaning it primarily affects boys, who inherit the disease through their mothers. If girls are affected, the condition is typically much less severe than in boys. For more, see Causes/Inheritance.

What is the progression of myotubular myopathy?

Myotubular myopathy is congenital (present at birth). If respiratory insufficiency is compensated for, infants may survive beyond infancy, after which the weakness appears nonprogressive.

What is the status of research on myotubular myopathy?

In recent decades, MDA-supported researchers discovered that defects in or loss of a previously unknown protein called myotubularin cause myotubular myopathy. MDA continues to support scientists in their quest to understand the molecular basis of myotubular myopathy and to find effective treatments. See Research.

See also Taking a Closer Look at Myotubular Myopathy: A range of outcomes.

What are autosomal centronuclear myopathies?

Autosomal centronuclear myopathies are relatively mild forms of centronuclear myopathy, a group of inherited myopathies that causes problems with the tone and contraction of skeletal muscles. They are called autosomal in reference to their inheritance pattern. The genetic mutations that underlie these myopathies are not on the X or Y (sex) chromosomes; they’re on the autosomes, or numbered chromosomes.

Autosomal dominant means only one copy of the flawed gene is enough to cause the disease. Autosomal recessive means two copies, one from each parent, are required for the disease to occur.

What are the symptoms of autosomal centronuclear myopathies?

Autosomal centronuclear myopathies are rarely fatal in childhood and do not seriously weaken the respiratory muscles the way the X-linked form does (see above). Weakness is diffuse but generally has a preference for either the proximal (near the center of the body) or distal (away from the center of the body) muscles. Drooping of the upper eyelids is common. Contractures may occur.

What causes autosomal centronuclear myopathies?

Several genes have been found that, when flawed, cause autosomal forms of centronuclear myopathy. One gene is for the amphiphysin 2 protein, which normally is involved in maintenance of the membrane surrounding muscle fibers. Another gene is for the dynamin 2 protein, which is part of the transportation system for substances inside cells. A third is for myogenic factor 6, a protein that helps regulate muscle development and regeneration. For more, see Causes/Inheritance.

What is the progression of autosomal centronuclear myopathies?

Autosomal dominant centronuclear myopathy (the dynamin 2 type) often has a very gradual onset and is slowly progressive. It may not cause a person to seek medical attention until young adulthood. Autosomal recessive centronuclear myopathies (the dynamin 2 and myogenic factor 6 types) tend to begin earlier and be more severe. Children with autosomal recessive centronuclear myopathies typically have some neuromuscular impairment as they grow and develop.

What is the status of research on autosomal centronuclear myopathies?

In recent years, MDA-supported scientists have learned that centronuclear myopathies encompass a larger group of diseases than just X-linked myotubular myopathy, and that these types often have a better prognosis than the X-linked type. Researchers are building on this knowledge to deepen their understanding of centronuclear myopathies and to find effective treatments. See Research.

See also Taking a Closer Look at Myotubular Myopathy: A range of outcomes, an article that covers the centronuclear myopathies, including myotubular myopathy.