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

• Adrenoleukodystrophy
• Amyothrophic Lateral Sclerosis
• Kugelberg-Welander Syndrome

Neurologic symptoms of Kennedy Disease typically begin between 20 and 50 years of age. Uncontrollable twitching of muscles (fasciculations) is usually the first symptom of this disorder. Twitching in the muscles of the face, trunk and/or arms and legs slowly progresses to muscle weakness and wasting. The lips, tongue, mouth, chin, throat and vocal chords may be affected. Some patients may have difficulty with speech and swallowing (dysphagia). Some affected individuals have muscle cramps and others have rhythmic, involuntary movements (action tremors). Some patients with Kennedy Disease may only be affected on one side of the body. Abnormally large calves of the legs (hypertrophied calves) have been found in almost half of the patients with this disorder.
Difficulty walking and a tendency to fall may also occur. Climbing stairs may be difficult 10-20 years after onset of symptoms. Approximately one-third of those affected will require a wheel chair 20 years after the onset on Kennedy disease. Most individuals with Kennedy disease have a normal life expectancy. Approximately 10% of elderly, non-ambulatory patients are at risk for life-threatening breathing problems.

Androgen insensitivity leads to symptoms that occur in adolescence such as abnormal swelling of the breasts (gynecomastia). Sexual function is normal until the onset of the disease at which time the patient may not be able to achieve an erection. A decrease or lack of sperm may cause infertility.
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Kennedy Disease is inherited as an X-linked recessive genetic trait. This condition is caused by a mutation in the androgen receptor (AR) gene that has been mapped to Xq11-q12. Individuals with Kennedy disease have more than 35 extra copies (trinucleotide repeats) of the CAG repeat region of the AR gene.

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 bands that are numbered. For example, "chromosome Xq11" refers to band 11 on the long arm of the X chromosome . The numbered bands specify the location of the thousands of genes that are present on each chromosome.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but 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 of their X chromosomes are carriers for 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. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male can not pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
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Kennedy Disease affects approximately one in 50,000 male births. This condition is known to occur in Caucasian and Asian ethnic groups. Kennedy disease is more common in the Japanese population than any other ethnic group.
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Symptoms of the following disorders can be similar to those of Kennedy disease. Comparisons may be useful for a differential diagnosis:

Adrenoleukodystrophy (ALD) is one of many different leukodystrophies. The adolescent or adult onset form of the disorder is called adrenomyeloneuropathy and symptoms of this form of ALD may be similar to those of Kennedy disease. Symptoms typically appear between the ages of 21 and 35. They may include progressive leg stiffness, spastic partial paralysis of the lower extremities and ataxia (clumsiness in walking). Decreased function of the sex glands may be present. Adult onset ALD progresses slowly, however it can ultimately result in deterioration of brain function. (For more information on this disorder, choose "adrenoleukodystrophy" as your search term in the Rare Disease Database.)

Amyotrophic lateral sclerosis is a disease of muscle nerve cells called motor neurons. It generally affects both the upper and lower body and results in the progressive wasting and weakening of those muscles that have lost their nerve supply. There are a number of different forms of ALS, all exhibiting some of the classical symptoms. (For more information on this disorder, choose "amyotrophic lateral sclerosis" as your search term in the Rare Disease Database.)

Kugelberg-Welander syndrome is a type of spinal muscular atrophy and is inherited as an autosomal recessive genetic trait. Major symptoms may include wasting and weakness in the muscles of the arms and legs, twitching, clumsiness in walking, and eventually loss of reflexes. Kugelberg-Welander syndrome is not apparent at birth but typically appears during the first ten to twenty years of life. (For more information on this disorder, choose "Kugelberg-Welander syndrome" as your search term in the Rare Disease Database.)
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Diagnosis
The diagnosis of Kennedy disease can be confirmed by performing molecular genetic testing on a blood specimen. Individuals with greater than or equal to 38 repeats of the CAG repeat region of the androgen receptor gene have Kennedy disease. Individuals with 35, 36 or 37 repeats may or may not have Kennedy disease depending on their symptoms. Longer repeat number has been associated with earlier onset of disease and more rapid progression, but this is not the case for all affected individuals.

Treatment
Treatment of Kennedy Disease is symptomatic and supportive. Physical therapy may be prescribed and braces and walkers may be helpful. Neither antiandrogen therapies nor testosterone are effective therapies. Some patients have breast reduction surgery because of gynecomastia.

Genetic counseling may be of benefit for patients and their families.
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Research on inherited disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future. Since scientists know the area where the Kennedy Disease gene is located on the X chromosome, it is hoped that once the gene is isolated it can be studied to determine the biochemical defect that causes this disorder.

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