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Kennedy Disease

NORD is very grateful to Joseph Kim, NORD Editorial Intern from the University of Notre Dame, and Albert La Spada, MD, PhD, FACMG, Professor of Pediatrics and Cellular & Molecular Medicine; Vice Chair and Division Head of Genetics, Department of Pediatrics & Rady Children's Hospital-San Diego; Associate Director, Institute for Genomic Medicine, University of California, San Diego, for assistance in the preparation of this report.

Synonyms of Kennedy Disease

  • KD
  • Kennedy's syndrome
  • SBMA
  • spinal and bulbar muscular atrophy
  • spinal bulbar muscular atrophy
  • X-linked spinal and bulbar muscular atrophy
  • X-linked spinal bulbar muscular atrophy

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Kennedy disease is a rare, X-linked slowly progressive neuro-muscular disorder. Kennedy disease is typically an adult-onset disease, where symptoms occur mainly between the ages of 20 and 50. The disease is characterized by symptoms such as muscle weakness and cramps in the arms, legs, and facial area, enlarged breasts, and difficulty with speaking and swallowing (dysphagia). Kennedy disease affects fewer than 1 in 150,000 males and does not typically occur in females, who are protected by their low levels of circulating testosterone, accounting for the sex-limited inheritance pattern in this disorder. Treatment is symptomatic and supportive and life expectancy is normal, though a small percentage of patients (~ 10%) succumb to the disease in their 60’s or 70’s.

Kennedy disease is named after William R. Kennedy, MD, who described this condition in an abstract in 1966 and a full report in 1968.


Affected individuals begin to develop neurological symptoms between 20 to 50 years of age. These early symptoms include:

· Weakness/cramps in arm and leg muscles
· Face, mouth, and tongue muscle weakness
· Difficulty with speaking and swallowing (dysphagia)
· Twitching (Fasciculations)
· Tremors and trembling in certain positions
· Enlarged breasts (gynecomastia)
· Numbness
· Infertility
· Testicular atrophy

The disease affects the lower motor neurons that are responsible for the movement of many muscles in the legs, arms, mouth, and throat. Affected individuals will show signs of twitching, often in the tongue, followed by muscle weakness and problems with facial muscles. These neurons, which connect the spinal cord to the muscles, become defective and die, so the muscles cannot contract. The destruction of these nerves is the main reason for the numbness, muscle weakness, and inability to control muscle contraction. With lack of normal neuromuscular function, a patient may experience hypertrophied calves in which the calf muscles thicken due to muscle cramps. In some cases, patients may also have one side of the body more affected than the other side.

The disease also affects nerves that control the bulbar muscles, which are important for breathing, speaking, and swallowing. Androgen insensitivity can also occur, sometimes beginning in adolescence and continuing through adulthood, characterized by enlarged breasts, decreased masculinity, and infertility. Patients may experience problems such as low sperm count and erectile dysfunction.


Kennedy disease is an X-linked genetic disorder that occurs primarily in males. Very rarely, female carriers of the abnormal gene may show symptoms.

Kennedy disease is caused by a mutation in a gene that encodes for a protein known as the androgen receptor (AR) and was mapped to band Xq11-q12 on the X chromosome. The instructions within every gene consist of different arrangements of four basic chemicals (nucleotide bases) called adenine (A), cytosine (C), guanine (G), and thymine (T). Individuals with the disease have an unstable section in the AR gene, which is due to an excessive number of CAG trinucleotide repetitions in the DNA sequence. An unaffected individual has 10-35 CAG repeats in the AR gene while a person with Kennedy disease has more than 36 CAG repeats in the gene.

The androgen receptor is in the cytoplasm of a cell where it responds to signals from male sex hormones (androgens). These receptors are abundant in many body tissues such as the skin, kidney, prostate, the central nervous system and motor neurons in the spinal cord. In an unaffected person, the androgen hormone will bind to the receptor, and then the hormone-receptor complex will relocate into the nucleus, where it will signal genes to increase protein production for various functions.

In Kennedy disease, the exact mechanism for neuronal impairment is unknown, but it has to do with an altered functioning of the androgen receptor.

Chromosomes are present in the nucleus of all human cells and contain an individual’s genetic information. Normal individuals contain 23 pairs of chromosomes for a total of 46. There are 22 autosomes (chromosomes that are not sex chromosomes) numbered 1-22, and sex chromosomes labeled X and Y. Normal males have one X and one Y chromosome, while normal females have two X chromosomes. Each chromosome has two arms: a short arm labeled "p" and a long arm labeled "q". These chromosomes are even further divided into numbered bands. For example, "chromosome Xq11" refers to band 11 on the long arm of the X chromosome. These bands are specific locations for the thousands of genes located on individual chromosomes.

An abnormal gene on the X chromosome causes X-linked disorders, such as Kennedy disease. Normal females have two X chromosomes, in which one is an activated chromosome and the other is inactivated. Female carriers for Kennedy disease typically do not show symptoms because the androgen receptor must bind to its ligand, testosterone, to translocate to the nucleus and perform its functions. As females have low circulating levels of testosterone, Kennedy disease female carriers do not activate their mutant androgen receptors, thus rendering the mutant state of the androgen receptor protein innocuous. Males have only one X chromosome and will develop Kennedy disease if they inherit the X chromosome containing the disease gene. Affected males with X-linked disorders will always pass the gene to their daughters, but will only pass their normal Y chromosome to their sons. Therefore, all of the daughters of an affected male will be carriers for the disease, while sons of an affected male will not have the disease. Sons of female carriers have a 50 percent chance of inheriting the disease, while daughters have a 50 percent chance of becoming carriers.

Affected Populations

Kennedy disease affects fewer than 1 in 150,000 males and is very rare in females. Kennedy disease has been diagnosed in the USA, Europe, Asia, South America, and Australia. The Japanese population appears to have a very high prevalence of Kennedy Disease because of a founder effect.

Related Disorders

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 (AMN), 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 (ALS) is one of a group of disorders known as motor neuron diseases. It is characterized by the progressive degeneration and eventual death of nerve cells (motor neurons) in the brain, brainstem and spinal cord that facilitate communication between the nervous system and voluntary muscles of the body. Ordinarily, motor neurons in the brain (upper motor neurons) send messages to motor neurons in the spinal cord (lower motor neurons) and then to various muscles. ALS affects both the upper and lower motor neurons, so that the transmission of messages is interrupted, and muscles gradually weaken and waste away. As a result, the ability to initiate and control voluntary movement is lost. Ultimately, ALS leads to respiratory failure because affected individuals lose the ability to control muscles in the chest and diaphragm. ALS is often called Lou Gehrig's disease. (For more information on this disorder, choose "amyotrophic lateral sclerosis" as your search term in the Rare Disease Database.) As it turns out, as many as 10% of Kennedy disease patients may be misdiagnosed with ALS prior to determining that they really have Kennedy disease.

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.)

Myasthenia gravis is a neuromuscular disorder primarily characterized by muscle weakness and muscle fatigue. Although the disorder usually becomes apparent during adulthood, symptom onset may occur at any age. The condition may be restricted to certain muscle groups, particularly those of the eyes (ocular myasthenia gravis), or may become more generalized (generalized myasthenia gravis), involving multiple muscle groups. Most individuals with myasthenia gravis develop weakness and drooping of the eyelids (ptosis); weakness of eye muscles, resulting in double vision (diplopia); and excessive muscle fatigue following activity. Additional features commonly include weakness of facial muscles; impaired articulation of speech (dysarthria); difficulties chewing and swallowing (dysphagia); and weakness of the upper arms and legs (proximal limb weakness). In addition, in about 10 percent of cases, affected individuals may develop potentially life-threatening complications due to severe involvement of muscles used during breathing (myasthenic crisis). Myasthenia gravis results from an abnormal immune reaction in which the body's natural immune defenses (i.e., antibodies) inappropriately attack and gradually destroy certain receptors in muscles that receive nerve impulses (antibody-mediated autoimmune response). (For more information on this disorder, choose "Myasthenia gravis" as your search term in the Rare Disease Database.)

Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic muscle disorder with onset during adulthood most often between 40 and 60 years of age. OPMD is characterized by slowly progressive muscle disease (myopathy) affecting the muscles of the upper eyelids and the throat. Affected individuals may develop drooping of the eyelids (ptosis), double vision (diplopia) and/or difficulty swallowing (dysphagia). Eventually, additional muscles may become involved including those of the upper legs and arms (proximal limb weakness). In some cases, muscle weakness of the legs may eventually cause difficulty walking. OPMD may be inherited as an autosomal dominant or recessive trait. ??OPMD belongs to a group of rare genetic muscle disorders known as the muscular dystrophies. These disorders are characterized by weakness and atrophy of various voluntary muscles of the body. Approximately 30 different disorders make up the muscular dystrophies. The disorders affect different muscles and have different ages of onset, severity and inheritance patterns. Unlike OPMD, most forms of muscular dystrophy have onset during childhood or adolescence. (For more information on this disorder, choose "Oculopharyngeal muscular dystrophy" as your search term in the Rare Disease Database.)

Sandhoff disease is a lipid storage disorder characterized by a progressive deterioration of the central nervous system. The clinical symptoms of Sandhoff disease are identical to Tay-Sachs disease. Sandhoff disease is an autosomal recessive genetic disorder caused by an abnormal gene for the beta subunit of the hexosaminidase B enzyme. This gene abnormality results in a deficiency of hexosaminidase A and B that results in accumulation of fats (lipids) called GM2 gangliosides in the neurons and other tissues. (For more information on this disorder, choose "Sandhoff disease" as your search term in the Rare Disease Database.)

Polymyositis is a systemic connective tissue disorder characterized by inflammatory and degenerative changes in the muscles, leading to symmetric weakness and some degree of muscle atrophy. The areas principally affected are the hip, shoulders, arms, pharynx and neck. (For more information on this disorder, choose "Polymositis" as your search term in the Rare Disease Database.)

Guillain-Barré syndrome (GBS) is a rare, rapidly progressive disorder that consists of inflammation of the nerves (polyneuritis) causing muscle weakness, sometimes progressing to complete paralysis. Although the precise cause of GBS is unknown, a viral or respiratory infection precedes the onset of the syndrome in about half of the cases. This has led to the theory that GBS may be an autoimmune disease (caused by the body's own immune system). Damage to the covering (myelin) of nerve axons (the extension of the nerve cell that conducts impulses away from the nerve cell body) results in delayed nerve signal transmission. This causes weakness of the muscles that are supplied by the damaged nerves. The following variants of GBS (acute inflammatory neuropathy or acute inflammatory demyelinating polyradiculoneuropathy) are recognized: Miller Fisher syndrome, acute motor-sensory axonal neuropathy, and acute motor axonal neuropathy. (For more information on this disorder, choose "Guillain-Barré syndrome" as your search term in the Rare Disease Database.)

Standard Therapies

A diagnosis of Kennedy disease is suspected based on physical signs and symptoms. Diagnosis can be confirmed by molecular genetic testing on a blood sample for CAG trinucleotide repeat expansion in the AR gene. Individuals with greater than 36 CAG trinucleotide repeats in the AR gene are diagnosed with the condition.

Clinical Testing and Work-Up
Annual examinations to assess muscle strength may be appropriate.

Currently, there is no known treatment or cure for Kennedy disease. Physical therapy, occupational therapy, and speech therapy are commonly used to adapt to the progressing disease and maintain an individual’s skills. Braces, walkers, and wheel chairs are used for ambulation. Breast reduction surgery is sometimes used as needed in patients with gynecomastia. Testosterone is not an appropriate treatment, as it can make the disease worse.

Investigational Therapies

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

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources, contact:

Contact for additional information about Kennedy disease:

Albert La Spada, MD, PhD, FACMG
Professor of Pediatrics and Cellular & Molecular Medicine
Vice Chair and Division Head of Genetics
Department of Pediatrics & Rady Children's Hospital-San Diego
Associate Director, Institute for Genomic Medicine
University of California, San Diego
Sanford Consortium for Regenerative Medicine Building
2800 Torrey Pines Scenic Drive, Rm 3003
La Jolla, CA 92037-0642
Phone: (858)-246-0149
Fax: (858)-246-0162

Kennedy Disease Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at

Other Organizations:


Russman BS. Spinal Bulbar Muscular Atrophy. In: The NORD Guide to Rare Disorders, Philadelphia, PA: Lippincott, Williams and Wilkins; 2003: 636.

La Spada A. (Updated October 13, 2011). Spinal and Bulbar Muscular Atrophy. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at Accessed June 28, 2012.

Barkhaus PE, Verman S. Kennedy disease. Emedicine. Updated May 30, 2012. Accessed June 28, 2012.

NINDS Kennedy's Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). . Last Updated August 2, 2011. Accessed June 28, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spinal and Bulbar Muscular Atrophy, X-Linked 1; SMAX1. Entry No: 313200. Last Edited September 23, 2010. Available at: Accessed June 28, 2012.

About Kennedy’s Disease. Kennedy Disease Association. Accessed June 28, 2012.

Spinal and bulbar muscular atrophy . Genetics Home Reference. Reviewed May 2006. Accessed June 28, 2012.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2012/07/09 00:00:00 GMT+0

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