FACTS ABOUT KENNEDY DISEASE
(SBMA)

What is it called!?

A common name is Kennedy Disease. It is also referrred to as Kennedy's Disease or Kennedy Syndrome or just KD. It gained this name from Dr. W. R. Kennedy, a neuromuscular researcher who was among the first to identify the disease as separate from other neurological conditions.
It can be also called by other names including spinal and bulbar muscular atrophy, SBMA, bulbo-spinal muscular atrophy, X-linked spinal and bulbar muscular atrophy, X-SBMA, X-linked spinobulbar muscular atrophy, hypertrophy of the calves, X-chromosonal recessive bulbospinal neuronopathy, X-BNS, Kennedy-type spinal and bulbar muscular atrophy, Kennedy-Stefanis Disease, SMAX1,

What are the symptoms?

Kennedy Disease, also known as SBMA, is a progressive adult-onset neurodegenerative disorder resulting from the loss of lower motor neurons. Kennedy disease is a form of motor neuron disease that is slowly progressive, only affects males, and causes only "lower motor neuron" weakness, atrophy, and fasciculations, without spasticity and hyperreflexia.
Uncontrollable twitching (fasciculations) followed by weakness and wasting of the muscles becomes apparent sometime after the age of fifteen. However, noticeable weakness usually starts in adulthood, in the third to fifth decade of life, is often associated with muscle cramps, and is symmetrical and proximal, affecting initially the hip & shoulder muscles.
Affected males first observe reduced stamina, with difficulty walking distances and problems getting out of low seats. Initial signs are often mistaken for aging. Mobility continues to decrease slowly. In addition SBMA patients frequently exhibit bulbar muscle weakness and atrophy. The muscles of the face, lips, tongue, mouth, throat, vocal cords, trunk, and upper extremities may be affected.
Fasciculations of the face, lips, and tongue are frequently observed. Other features that aid in diagnosis, but are not always present, are gynecomastia and infertility.
Female carriers are clinically asymptomatic.
See a summary of clinical features for a more detailed list of signs and symptoms at Kennedy Disease Signs and Symptoms.

Can it be misdiagnosed?

Kennedy's Disease is very rare. It so rare that it is in a class known as "orphan diseases". Its physical manisfestations are similar to many other neurodegenerative conditions, including Lou Gehrig's Disease (amyotrophic lateral sclerosis, or ALS), multiple sclerosis (MS), spinocerebellar ataxia type 1 (SCA1), adult onset spinal muscular atrophy (SMA), lead poisoning, pesticide poisoning, spinal cord injury, and other diseases and injuries affecting the neuromuscular system. Therefore, it is easy for a practitioner to ascribe to another cause the symptoms a patient may have.

How is it definitively diagnosed?

Many medical tests may be conducted initially. These are used to rule out other more life-threatening conditions. Physical exams will determine strength, balance, and reflexes. Imaging technology, such as X-rays, CT scans, and MRIs may be used to check the skull, spine, brain, and nerve tissue. Blood and other bodily fluid tests may be conducted to rule out poisoning or metabolic disorders. Neurologic tests such as nerve conduction studies and electromyography may be used to determine the operation of muscles and nerves. Biopsies may be performed to microscpically analyze muscle and nerve tissue.
However, the definitive diagnosis for Kennedy Disease is by a DNA analysis. This molecular test is accurate and inexpensive to perform, requiring only a blood sample. A simple and accurate blood test for Kennedy disease is available through the Molecular Diagnostic Laboratory at the University of Pennsylvania and the University of Texas Medical Center at Houston, among others.

What causes it?

Kennedy disease is caused by a specific mutation (an expansion of the normally polymorphic CAG trinucleotide repeat) in the first exon of the androgen receptor gene (which encodes polyglutamine tracts) which is located on the X-chromosone. In the disease, a normal three-base sequence in the genetic code -- cytosine, adenine and guanine, or CAG -- is abnormally repeated. The CAG repeat range in the general population is approximately 12 to 32 repeats. In patients with Kennedy disease, the repeats may number as many as 40 to 55 repeats.
Androgen activity in the central nervous system is mediated by the androgen receptor. The expanded number of repeats apparently interferes with the activity of androgen receptors in cells. Androgen receptor abnormality appears to lead to the motor neuron degeneration observed in Kennedy disease. However, this area is still under research. The biochemical effects of these expansions have not yet been positively elucidated and therefore effective therapeutic intervention cannot currently be designed for affected individuals. However, the identification of the number of repeats through relatively inexpensive and easy blood testing provides a positive means of diagnosis. The availability of accurate prenatal testing has already had a significant impact on the welfare of the patient groups.
Expansion of trinucleotide repeats has subsequently been associated with several other neuromuscular disorders, including myotonic dystrophy, hereditary dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich's ataxia, fragile X syndrome, spinocerebellar ataxia types 1 and 2 (SCA1 and SCA2), Machado-Joseph disease (MJD/SCA3), and Huntington's disease (HD).
At present there are no effective treatments to slow or prevent the progression of the disease.
Symptoms appear when the repeats exceed about 40. A larger number of repeats has been suggested to cause symptoms to begin earlier in life and progress more rapidly.

Who contracts the disease?

Because of its mechanism as an X-linked disorder, men who are possess the trait get the disease (have the symptoms). The theory is that a man has but one X-chromosone and is therefore affected by its effects if it is defective. Women who possess the trait do not have symptoms. The theory is that a woman usually has two X-chromosones, of which one is normal and suppresses the effects of the abnormal chromosone. Such a woman is thus less affected by the a defective X chromosone if only one of them is defective. People who possess a genetic trait but are not physically affected are known as carriers: thus women who have the Kennedy's Disease genetic trait are said to be carriers of the disease. Because the disease is genetic in origin, it can be passed to a carrier's offspring.
The chance that an affected male will pass his defective X-chromosone to his son is almost zero: boys get their one X-chromosone from their mother. The chance that a affected male will pass his defective X-chromosone to his daughter approaches 100%: girls get one of their two X-chromosones from their father, the other from their mother.
The chance that a carrier female will pass her defective X chromosone to her son is 50%: boys get their one X chromosone from their mother. They have an equal chance of getting either their mother's unaffected X chromosone or her defective X-chromosone. The chance that a carrier female will pass her defective X chromosone to her daughter is also 50%: girls get one of their two X chromosones from their father, the other from their mother. As with her brother's case, she might get an unaffected or a defective X-chromosone.
If an affected male has only sons, the disease will die out in his generation. Likewise, if a carrier female passes only unaffected (non-defective) X-chromosones to her children, then the disease will stop at that generation. If an affected male fathers daughters, or if a carrier female passes the defective X-chromosone to her offspring, then the disease will continue in the family tree.
In the case where only girls are born to a family, it may be said that the disease "skips a generation". However, this is only apparently true because females may be carriers and not manifest clinical disease symptoms. Thus, some of the daughters may have the trait and be carriers, and others may not have the trait and not be carriers. The chance is 50% of either occurring.
In my personal situation, my mother came from a family of five girls and no boys. Of course, none of the girls developed SBMA. However, it has become apparent that two were carriers: my Mom and one of her sisters. Currently I have been posiively diagnosed, as have one of my male cousins.

What are the current treatment options?

Currently, no demonstrably effective treatment exists for Kennedy's Disease. Carefully managed exercise and physical therapy can help the patient maintain as much strength as possible. Rehabilitation therapy can help the patient learn to manage physical limitations. Psycho-social counselling can help the patient adapt mentally to physical limitations. Assistive living therapy can help a patient whose symptoms have progressed to the extent that normal daily activities are challenging.
An experimental protocol using the anti-androgen luprolide (Lupron) has been set up at Ohio State University by Dr. Jerry Mendell. There is good reason to believe that this agent, which is now being used in the treatment of prostate cancer, may block the toxic effects of the mutated androgen receptor in Kennedy's disease. Physicians interested in the experimental treatment protocol should contact Patrick Vaglienti at Ohio State University (614) 292-1234).
Another approach currently being investigated is using androgen administration, which can be via injection, oral, or transdermal patch. This approach is to boost the testosterone levels which would promote muscle growth and strength. This clinical trial showed increased muscle strength, but the long term benefits are yet unclear. In addition, androgen therapy may result in negative side effects which pose risk to the patient.
Because of its rarity, Kennedy Disease does not have its own support group or web site. However, other groups have reached out to offer support. Patients are urged to contact local chapters of ALS, MS, SMA, and other groups, or to make contact over the internet. Because of the similarity in symptoms, advice and support for Kennedy Disease patients is abundant from other kinds of patients and groups.

Are there any "non-standard" treatments?

Every illness that has no specific cure has numerous folk or non-traditional treatments, diets, and therapies. Consider the common cold and all the remedies available. A patients's best recourse is to discuss the issue with his physician. Ask for consultations with physicians of other specialties.
Kennedy disease has other implication in addition to neuromuscular deficit. Diet and exercise become more important. Diabetes mellitus may be related in some way. Androgen deprivation is emerging as an important risk factor for osteoporosis in men. There is evidence that testosterone deficiency causes significant bone mass loss.
Contact other support groups. Do your own research on the Internet, at the library, at a local university, or at a local hospital library. Discuss your results with your physician. Above all, do no harm. But never give up.

What does the future hold?

Most research appears to be centered on trying to understand the exact mechanism in which expansion of trinucleotide repeats causes the symptoms previously indicated. Dr. Kenneth H. Fischbeck of the University of Pennsylvania Medical School, the researcher who identified the androgen receptor gene mutation as cause of the symptoms, is investigating the disorder at the molecular biological level. Other researchers are correlating the type and severity of symptoms and age of onset with population genetic factors and the number of CAG repeats.

There are some researchers who are looking for a cure or treatment. However, the basic research to determine the exact mechanism remains to be completed. Some current research is aimed at developing a model system for Kennedy Disease by introducing the mutated gene into cultured neurons and transgenic mice. I personally donated some tissue samples for that purpose. The hope is that such a model system could be used to develop a rational and effective treatment in the future.
For example, SCA1 is another CAG-repeat disorder. "For the 10,000 or so Americans who have SCA1 and their families, this discovery means that we will soon have a relatively inexpensive test to confirm diagnosis, even though we don't yet have a cure," said NINDS director Dr. Murray Goldstein. "In addition, new techniques to screen for these repeats may be a shortcut to finding genes causing other disorders; the sooner we find a disease-related gene, the we can learn what goes wrong in the cell. There may be common mechanisms of action, and this study provides a clear lead."

The National Institute of Neurological Disorders and Stroke (NINDS), one of the National Institutes of Health located in Bethesda, MD, is the nation's leading supporter of research on the brain and nervous system and a lead agency for the Congressionally mandated Decade of the Brain. See Current Rare Diseases Clinical Trials for more information. Internationally, there is significant research being conducted in Japan, France, and Italy, among other places.

To help you in your own personal research, or to provide information to your family practitioner, I've begun a SBMA References Page. It, too, is a work in progress. :-)