Information on the following diseases can be found in the Related Disorders section of this report:

• Emery-Dreifuss Muscular Dystrophy
• Kearns-Sayre Syndrome
• Landouzy-Dejerine Muscular Dystrophy
• Limb-Girdle Muscular Dystrophy
• Myotonic Dystrophy
• Nemaline Myopathy
• Oculogastrointestinal Muscular Dystrophy

X-linked myotubular myopathy is characterized by severe respiratory distress caused by weakness of the respiratory muscles. Infants with this form of the disease may have weakness of the jaw, tongue, lips, cheeks, mouth, throat, and neck muscles, causing poor sucking and an inability to swallow. The upper eyelids may droop downward, and paralysis may be present. Infants may also have excessive birth length, long fingers and toes, and joint contracture (a permanent shortening that produces distortion or deformity).

Like the X-linked form of the disease, autosomal recessive myotubular myopathy is characterized by respiratory distress. Weakness of the upper eyelid, jaw, tongue, lips, mouth, throat, and neck may be present. The generalized muscle weakness that is typically present at infancy or childhood becomes more severe by adolescence or young adulthood. As the disease progresses, curvature of the spine may become apparent, and seizures may develop. Many patients with this form of the disease have a large head, long and narrow face, and high arched palate.

Early symptoms of autosomal dominant myotubular myopathy may be a clumsy gait (walk) and general weakness of the hips and shoulders. Walking becomes increasingly difficult, and eventually, the use of a wheelchair may be necessary. Some patients may have facial weakness, but the muscles of the throat and eyes usually remain unaffected.

Myotubular myopathy can be inherited as an autosomal dominant, autosomal recessive, or X-linked genetic trait.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy, regardless of the sex of the resulting child.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, he or she will be a carrier of the disease, but usually will not show symptoms. The risk of two carrier parents both passing the defective gene and having an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance of having a child who receives normal genes from both parents and is genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than do unrelated parents of both carrying the same abnormal gene, which increases the risk of having children with a recessive genetic disorder.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes; however, one of the X chromosomes is "turned off", and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one X chromosome are carriers of that disorder. Carrier females usually do not display symptoms of the disorder, because it is usually the X chromosome with the abnormal gene that is turned off. Males have one X-chromosome. If a male inherits an X chromosome that contains a disease gene, he will develop the disease. A male with an X-linked disorder passes the disease gene to all of his daughters, and the daughters will be carriers. A male cannot pass an X-linked gene to his sons because the Y chromosome (not the X chromosome) is always passed to male offspring. A female carrier of an X-linked disorder has a 25% chance with each pregnancy of having a carrier daughter, a 25% chance of having a non-carrier daughter, a 25% chance of having a son affected with the disease, and a 25% chance of having an unaffected son.

The X-linked recessive form of myotubular myopathy has been mapped to the long arm of chromosome X (Xq28).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many numbered bands. For example, "chromosome Xq28" refers to band 28 on the long arm of chromosome X.

X-linked myotubular myopathy is a rare disease that affects only males. Autosomal recessive myotubular myopathy affects females slightly more often than males and has been described in many parts of the world. There appears to be a higher incidence among Americans of African descent; however, all races can be affected. Autosomal dominant myotubular myopathy affects males twice as often as females. There have been approximately 20 cases of this form of the disorder reported in the medical literature.

Disease comparisons may be useful for a differential diagnosis. Symptoms of the following disorders can be similar to those of myotubular myopathy.

Emery-Dreifuss muscular dystrophy is a rare and often slowly progressive form of muscular dystrophy. Onset is usually by the age of 10 years. Major symptoms may include muscle wasting and weakness, particularly in the muscles of the shoulder, upper arm, and calf. Cardiac abnormalities and complications are common. The disease can be X-linked recessive, autosomal dominant, or autosomal recessive. (For more information on this disorder, choose "Emery-Dreifuss Muscular Dystrophy" as your search term in the Rare Disease Database.)

Kearns-Sayre syndrome is a rare slowly progressive neuromuscular disorder characterized by immobility of the eye and eyelid droop. An atypical accumulation of pigmented material on the eye membrane may also be present. Other symptoms may include short stature, hearing loss, mild skeletal muscle weakness, heart block (a cardiac conduction defect), inability to coordinate voluntary movement, and impaired cognitive function. (For more information on this disorder, choose "Kearns-Sayre Syndrome" as your search term in the Rare Disease Database.)

Facioscapulohumeral muscular dystrophy, also called Landouzy-Dejerine muscular dystrophy, is a very rare neuromuscular disorder inherited as an autosomal dominant genetic trait. Weakness of the facial muscles, which give a mask-like appearance, as well as weakness of the shoulder girdle, may appear at anytime during the first two decades of life. The degree of muscle weakness can vary from slight to severe. A more severe form of the disease is apparent during infancy and has a rapid progression. (For more information on this disorder choose "Facioscapulohumeral Muscular Dystrophy" as your search term in the Rare Disease Database.)

At least 10 different disorders are included in the limb-girdle muscular dystrophies, which initially affect muscles around the hips and shoulder girdle. Most of the disorders are inherited as an autosomal recessive trait. The symptoms of limb-girdle muscular dystrophy usually first occur during childhood to young adulthood as pelvic muscle weakness. Shoulder weakness, which may lead to loss of mobility, usually occurs over the next 20-30 years. Other muscles may become involved as the disorder progresses. (For more information on this disorder, choose "Limb-Girdle Muscular Dystrophy" as your search term in the Rare Disease Database.)

Myotonic dystrophy is a rare disorder in which muscles lack the power to relax after contraction. Other disease characteristics include mental deficiency, hair loss, and cataracts. Although onset commonly occurs during young adulthood, the disease can present at any age and may vary in severity. The gene for myotonic dystrophy, located on chromosome 19, codes for a protein kinase found in skeletal muscle. (For more information on this disorder, choose "Myotonic Dystrophy" as your search term in the Rare Disease Database.)

Nemaline myopathy is a neuromuscular disease characterized by weakness and "floppiness" of skeletal muscles. Muscle weakness is typically most severe in the face, proximal limb muscles, and flexors in the neck; deep tendon reflexes may be depressed or absent. Six forms of the disorder based on age of onset and severity are currently recognized. The disorder can be inherited as an autosomal dominant or autosomal recessive genetic trait. (For more information on this disorder, choose "Nemaline Myopathy" as your search term in the Rare Disease Database.)

Oculogastrointestinal muscular dystrophy is a very rare form of muscular dystrophy that affects females more often than males. It is inherited as an autosomal recessive trait. The disorder is characterized by droopy eyelids (ptosis); loss of movement of the external eye muscles (external ophthalmoplegia); and a progressive condition in which the intestinal walls are unable to contract normally, causing abdominal pain, diarrhea, constipation, and malabsorption of nutrients. (For more information on this disorder, choose "Oculo-gastrointestinal Muscular Dystrophy" as your search term in the Rare Disease Database.)

Patients with the autosomal recessive and X-linked forms of myotubular myopathy may require the use of mechanical ventilation devices, such as positive end expiratory pressure (PEEP) machines.

Patients with the autosomal recessive form of myotubular myopathy who have seizures may benefit from anti-convulsant drugs.

Patients with the autosomal dominant form of myotubular myopathy may benefit from physical therapy and appliances, such as walkers and wheelchairs.

Genetic counseling may be beneficial to patients and their families. Other treatment is symptomatic and supportive.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Research is being conducted on mytotubular myopathy in Europe and the United States. It focuses on locating the genes responsible and better characterizing the seemingly unrelated medical problems that accompany this disorder.

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