• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
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Kennedy Disease


Last updated: 8/8/2023
Years published: 1994, 1996, 2003, 2012, 2015, 2018, 2023


NORD gratefully acknowledges Joseph Kim, NORD Editorial Intern from the University of Notre Dame, and Albert La Spada, MD, PhD, FACMGG, Distinguished Professor, Pathology & Laboratory Medicine, Neurology, and Biological Chemistry; Associate Dean for Research; Director, UCI Center for Neurotherapeutics, University of California Irvine, for assistance in the preparation of this report.

Disease Overview


Kennedy disease is a rare, X-linked slowly progressive neuromuscular disorder. Kennedy disease is typically an adult-onset disease, where symptoms present 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, fasciculations of the tongue / face, enlarged breasts and sometimes difficulty with speaking and swallowing (dysphagia). Kennedy disease affects approximately 1/200,000 people worldwide and mostly occurs in males. 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 due to swallowing complications (aspiration pneumonia, asphyxiation) resulting from the bulbar weakness.


Kennedy disease is named after William R. Kennedy, MD, who described this condition in an abstract in 1966 and a full report in 1968, although the disease was recognized in Japan previously, where the frequency is much more common.

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  • 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
  • spinobulbar muscular atrophy
  • X-linked spinobulbar muscular atrophy
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Signs & Symptoms

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 (proximal > distal)
· Face, mouth and tongue muscle weakness
· Difficulty with speaking and swallowing (dysphagia)
· Twitching (fasciculations)
· Tremors and trembling in certain positions
· Enlarged breasts (gynecomastia)
· Numbness
· Reduced fertility
· 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 show signs of twitching, often in the tongue, face and/or hand, 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 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. Some patients may 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 masculine appearance and infertility. Patients may experience problems such as low sperm count and erectile dysfunction.

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Kennedy disease is caused by a change (variant or mutation) in the AR gene that encodes for a protein known as the androgen receptor 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 abnormal 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, skeletal muscle and the central nervous system motor neurons in the spinal cord and brainstem. In an unaffected person, the androgen hormone will bind to the receptor and then the hormone-receptor complex will translocate into the nucleus, where it will signal genes to increase protein production for various functions. The exact mechanism for neuronal impairment is unknown, but it has to do with an altered functioning of the abnormal androgen receptor.

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

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 harmless.

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 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.

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Affected populations

Kennedy disease affects approximately 1/200,000 people worldwide 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.

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A diagnosis of Kennedy disease is suspected based on physical signs and symptoms, and sometimes family history. 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. It has recently been noted that Kennedy disease patients are at increased risk of developing heart disease and liver disease due to hyperlipidemia and insulin resistance. Some patients develop arrhythmias or occasionally hypertrophic cardiomyopathy, and hyperlipidemia and insulin resistance may predispose to coronary artery disease. Some patients display significant metabolic changes consistent with non-alcoholic fatty liver disease. Hence, Kennedy’s disease patients should receive an ECG and annual lipid, cholesterol and blood sugar testing.

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Standard Therapies

Currently, there is no known treatment or cure for Kennedy disease. Physical therapy, occupational therapy and speech therapy are commonly used to help patients adapt to progressing disease and maintain skills. Braces, walkers, and wheelchairs 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.

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Clinical Trials and Studies

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 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
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

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

For information about clinical trials conducted in Europe, contact:

Contact for additional information about Kennedy disease:

Albert La Spada, MD, PhD, FACMG
Distinguished Professor
Pathology & Laboratory Medicine, Neurology, and Biological Chemistry
Associate Dean for Research
Director, UCI Center for Neurotherapeutics
Vice Chair, Dept. of Pathology & Laboratory Medicine
Vice Chair, Dept. of Neurology
University of California Irvine School of Medicine
ISEB Room 2044
419 S. Circle View Drive
Irvine, CA 92697
Phone: (949)-824-7407
Email: alaspada@uci.edu

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

La Spada A. Spinal and Bulbar Muscular Atrophy. 1999 Feb 26 [Updated 2022 Dec 15]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1333/ Accessed August 7, 2023.

Barkhaus PE, Verman S. Kennedy Disease. Medscape. Sep 29, 2019. https://emedicine.medscape.com/article/1172604-overview Accessed August 7, 2023.

NINDS Kennedy’s Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). https://www.ninds.nih.gov/Disorders/All-Disorders/Kennedys-Disease-Information-Page Accessed August 7, 2023.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Spinal and Bulbar Muscular Atrophy, X-Linked 1; SMAX1. Entry No: 313200. Last Edited02/21/2019. Available at: https://omim.org/entry/313200 Accessed August 7, 2023.

Spinal and bulbar muscular atrophy. Genetics Home Reference. June 1, 2020. https://ghr.nlm.nih.gov/condition/spinal-and-bulbar-muscular-atrophy . Accessed August 7, 2023.

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Programs & Resources

RareCare® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations

National Organization for Rare Disorders