This is part of Rare diseases.
Diagnosis: Kennedy disease
Synonyms: Spinal bulbar muscular atrophy, SBMA
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Date of publication: 2009-04-06
Version: 2.1
Kennedy disease is an inherited neuromuscular disease characterised by slowly progressive wasting and weakening of the muscles. The disorder was first described in 1968 by American neurologist William R. Kennedy. Since then, some thirty different names have been used to describe the condition, including spinal bulbar muscular atrophy (SBMA) and X-linked spinal bulbar neuronopathy.
The physical manifestations of Kennedy disease are in many ways similar to another neurodegenerative disease known as amyotrophic lateral sclerosis or ALS (see separate information text in the rare disease database). However, Kennedy disease has a significantly slower progression, and it is therefore important to distinguish between the two diagnoses.
In Sweden only a few dozen individuals have been diagnosed with Kennedy disease. However, as the disease is rare and the symptoms may be mild, it is likely that there are more individuals with the condition who have not yet received an accurate diagnosis. A higher prevalence of Kennedy disease has recently been reported from western Finland.
The cause of Kennedy disease is a mutation in a gene encoding a protein known as the androgen receptor (AR). In individuals with the disease, a section of the AR gene is unstable. This instability is due to an excessive number of repetitions of a certain DNA-sequence, CAG. Normally there are 17-26 CAG repeats in the AR gene. If there are more than 40 repeats the individual will develop Kennedy disease, and the severity of the disease will increase with the number of excessive repetitions.
Androgen receptors reside in the cell (in the cytoplasm), where they respond to signals from male sex hormones (androgens). The receptors are present in many tissues in the body, including the central nervous system and the motor neurons (the nerve cells that regulate muscle activity) in the spinal cord and brain stem. When an androgen binds to the receptor, it relocates to the nucleus, where it signals to genes that respond by increasing the production of proteins. These proteins are involved in many reactions.
Owing to the genetic mutation that causes Kennedy disease, the androgen receptor is defective and impaired but activated androgen receptors accumulate in the cell cytoplasm instead of being stimulated to move into the cell nucleus. As a result, electrical and chemical signals that are exchanged between the motor neurons and the muscles are disturbed, and the muscles atrophy. Since the cell nucleus does not receive normal signals from the androgen receptor, the effects of the male sex hormones are reduced. Sensory nerves and autonomous nerves, that control sweating for instance, are also affected.
Another mutation in the androgen receptor gene causes the androgen insensitivity syndrome (see separate information text in the rare disease database).
Kennedy disease is an inherited X-linked recessive disorder. This means that the mutation causing the disease is located on the X chromosome, which is one of the sex chromosomes. While women have two X chromosomes, men have one X chromosome and one Y chromosome. Since the mutated gene is recessive, female carriers are protected by having a second X chromosome with a normal gene, whereas men who inherit the mutated gene develop the disease. X-linked recessive disorders are therefore found only in men, but are passed down via female carriers of the mutation. Sons of female carriers run a 50 per cent risk of inheriting the disorder, and daughters run the same risk of becoming carriers. A man with an X-linked recessive disorder cannot pass it down to his sons, but all his daughters will be carriers of the mutation.
The symptoms of muscle weakening and wasting associated with Kennedy disease usually present between the ages of 15 and 60 years. Muscle cramps and postural tremors (tremors that occur when attempting to maintain posture) are common and may present several years before muscle weakness has developed. The muscle weakness is proximal, meaning that the muscles closest to and in the trunk tend to be most affected. Small muscle contractions (fasciculations) in the musculature of the arms, legs, and trunk are also common. Muscle stretch responses are often weak or absent.
The bulbar muscles (relating to the throat, tongue, jaw, and face) are often affected 5 to 10 years after the onset of the disease. The symptoms include increased weakening of the facial muscles and twitches in the face and tongue. Swallowing difficulties (dysphagia) and speech difficulties (dysarthria) are other common symptoms. The symptoms may result in considerable functional disability. However, the degree of disability associated with the condition varies greatly and the experience of functional limitations in daily life is highly individual. Many people with Kennedy disease retain their ability to walk throughout their whole lives, while others may need a wheelchair. Individuals with the disorder are at increased risk of recurring pneumonia, as the cough and gag reflexes are weakened, which makes it easier for bacteria to spread from the upper respiratory tract down to the lungs.
Insensitivity to male sexual hormones presents as enlarged breast glands (gynaecomastia) and impaired sexual function. Reduced sex drive, infertility, impotence, and shrunken testicles are symptoms that affect approximately half of all individuals with Kennedy disease. Fertility problems associated with impaired sperm production may develop as the disease progresses. In mild cases of the disease, sexual function and fertility can be normal.
Other conditions associated with hormonal abnormalities, such as diabetes, sometimes also occur.
The characteristic symptoms, followed by a clinical neurological examination, should raise the suspicion of Kennedy disease.
A neurophysiological examination will show essentially normal peripheral nerve conduction. The sensory nerve conduction may, however, be slightly impaired. An EMG test (electromyography) may detect chronic denervation, indicating that the pathway between the spinal cord motor neurons and the muscle fibres is partially blocked.
In some cases, a muscle biopsy is performed. Like the EMG, it will show signs of denervation.
A blood sample often contains a low level of androgens (testosterone), and a high level of female sex hormones (estradiole).
The diagnosis is confirmed by DNA analysis. Prenatal diagnostics is possible.
There is currently no intervention that prevents the development of the disease. The treatment is therefore directed at easing the symptoms and compensating for functional limitations.
Individuals with Kennedy disease need to maintain regular contact with specialists in neurology and endocrinology. If the onset of symptoms occurs during the teens, contact may be established with a paediatric rehabilitation team. The team includes professionals from different disciplines with specialist knowledge about the impact of functional disabilities on daily life, health, and development. Support and treatment can be coordinated between the medical, pedagogical, psychological, and social support areas. In most cases, however, specialists from different areas of the adult health care system treat individuals with Kennedy disease.
In cases of swallowing and speech problems, the assistance of a speech therapist may be required. Many hospitals have an oral motor team working with evaluation and treatment of eating and swallowing difficulties.
A physiotherapist can provide advice on suitable forms of physical activity and design an appropriate exercise programme to maintain the functional level of the muscles as long as possible. Breathing exercises may be valuable.
Depending on the degree of the functional disability, assistance devices, new routines and individualized adaptations facilitate activities of daily living, such as ambulation, hygiene, dressing and undressing, and eating. If necessary, the home, the car, and the workplace can be adapted to individual needs. A physiotherapist or an occupational therapist should assist in determining what measures need to be taken.
It is important for young people and adults with Kennedy disease to be well informed about their condition. Professional psychological and social support should also be offered, and is normally provided by a psychologist or a rehabilitation counsellor. A rehabilitation counsellor also handles information about the provision of national and regional support, for example personal assistance services, home help services, and residential care facilities.
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Swedish neurologists are familiar with Kennedy disease. However, the resources needed to confirm the diagnosis are not available at all clinics.
Senior Physician Björn Lindvall, Muscle Centre, Örebro University Hospital, SE-701 85 Örebro, Sweden. Tel +46 19 602 10 00, email: bjorn.lindvall@orebroll.se.
Associate Professor Lars-Olof Ronnevi, Department of Neurology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Tel +46 8 517 700 00.
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To date, there is no Swedish association for individuals with Kennedy disease. There is, however, a liaison officer at the Swedish Association for Rare Disorders:
Rare Diseases Sweden, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se.
Rare Diseases Sweden is a federation of rare disease organizations, serving the interests of people with rare disorders.
NHR, The Swedish Association of Persons with Neurological Disabilities. Street address: St Eriksgatan 44, Stockholm. Mailing address: Box 490 84, SE-100 28 Stockholm, Sweden. Tel +46 8 677 70 10, fax +46 8 24 13 15, email:
nhr@nhr.se, Internet:
www.nhr.se.
As Kennedy disease is a very rare disorder, it may be difficult for individuals with the condition to make contact with other people in the same situation. There is an American Internet-based support group that provides the opportunity for individuals with Kennedy disease to meet online: email: info@kennedysdisease.org, Internet: www.kennedysdisease.org.
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There is ongoing genetic research into hereditary neurological and neuromuscular disorders, such as Kennedy disease, with the goal of developing effective treatments. Centres in the USA are at the forefront of this research and a prominent position in the field is held by Dr Kenneth H. Fischbeck at the University of Pennsylvania.
An information folder on Kennedy disease which summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2001-12-143). Address: SE-120 88 Stockholm, Sweden. Tel +46 8 779 96 66, fax +46 8 779 96 67, email: socialstyrelsen@strd.se. Postage will be charged for bulk orders.
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OMIM - Online Mendelian Inheritance in Man
Internet: http://www.ncbi.nlm.nih.gov/omim
Search: kennedy disease
GeneReviews (University of Washington)
Internet: www.genetests.org (select Genereviews)
Search: spinal and bulbar muscular atrophy
The Swedish Information Centre for Rare Diseases produced and edited this information material.
The medical expert who wrote the draft of this information material is Associate Professor Göran Solders, Karolinska University Hospital, Stockholm, Sweden.
The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.
An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.
Date of publication: 2009-04-06
Version: 2.1
Publication date of the Swedish version: 2008-11-10
For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden, tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.