Kennedy Disease

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Kennedy Disease is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


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

Disorder Subdivisions

  • None

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.

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




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.


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Muscular Dystrophy Association

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Kennedy's Disease Association

P.O. Box 1105

Coarsegold, CA 93614-1105

Tel: (559)658-5950

Fax: (559)658-5950



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

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Tel: (301)251-4925

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Tel: (888)205-2311

TDD: (888)205-3223


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