Symptoms of Kennedy's Disease (SBMA)

Any time I list the potential symptoms of Kennedy’s Disease, aka Spinal Bulbar Muscular Atrophy (SBMA), there is a tendency for someone to comment, “I have that. Do you think it’s Kennedy’s Disease?”

My answer is always the same. “I don’t know. You need to see your primary care doctor and discuss your symptoms with her/him.”

When my symptoms started, there was no DNA test for Kennedy’s Disease (SBMA). Most doctors and many neurologists did not know about SBMA. Neurologists put you through a series of tests, some not very pleasant, to help determine the cause of the symptoms. Most often, it was an educated guess based upon available evidence. In my case, I was diagnosed with ALS.

Several years later, another doctor diagnosed it as SBMA and sent me to see Dr. Fischbeck for a second opinion. I still remember walking into Dr. Fischbeck’s office that morning. He saw my gate, nodded his head, and said, “You have the walk.” He performed a DNA test and confirmed Kennedy’s Disease.

Today, because of the DNA test, a doctor can draw a little blood and send it off to a lab. Within a few weeks you will have an answer as to if you have Kennedy’s Disease. If not, you will still have to go through more testing, but at least SBMA is ruled out.

In regards to the list of symptoms below, those of us living with Kennedy’s Disease normally do not have all of them. We will have several and some might not appear until later in the progression. The most common early symptoms are severe cramping, hand tremors, unexplained fasciculations, and gynecomastia.

Please note there is a wealth of information available on the Kennedy’s Disease Association website (http://www.kennedysdisease.org/index.php/about-kennedys-disease/what-is-kennedys-disease).

SYMPTOMS (I apologize for the formatting problem below)

Neurological:
Bulbar Signs	The Bulbar muscles are those supplied by the motor nerves coming off the brain stem. They control breathing, swallowing, talking and other functions of the throat. Bulbar signs are problems with these functions.
Dysphagia	Trouble swallowing. (One of the Bulbar signs.)
Intention Tremor	Hand tremors when trying to do something.
Normal Babinski	Normal plantar response, ie., when the bottom of the foot is scraped, the toes bend down. An abnormal response would be an upward bending of the toes indicating a problem in the brain itself.
Lower Motor Neuropathy	The lower motor nerves are those that run from the spinal cord to the muscles that they stimulate to move. Loss of that nerve leads to weakness and wasting of the muscle.
Primary Sensory  Neuropathy	Numbness over certain areas. Loss of sensation.
Decreased or Absent Deep Tendon Reflexes	When a doctor taps the knee with his hammer there is no response.
Muscular:
Fasciculations	Twitching of small muscles without purposeful movement. These can be seen through the skin.
Cramps	Large muscle spasms.
Postural Tremor	Shaky muscles with certain positions.
Muscular Atrophy	Wasting and shrinkage of muscles that occurs when the lower motor nerve does not stimulate the muscle adequately.
Hypertrophied Calves	Calf muscles that become thicker because of cramps.
Thoracic:
Gynecomastia	Enlarged breasts.
Endrocrine
Androgen Deficiency	Loss of masculinizing effect (qualities that are perceived as masculine).
Estrogen Excess	More of an apparent estrogen effect because of the lost of masulinizing effect.
Genito-Urinary:
Impotence	Erectile dysfunction.
Reduced Fertility	Low sperm count.
Testicular Atrophy	Testicles become smaller and less functional.
Miscellaneous Characteristics:
Late Apparent Onset	Symptoms could become apparent in 20's or 30's, but might not appear until the 60's or 70's.
Slow Progression	Near-normal lifespan.
Asymmetry of Clinical Signs	Muscles of one side may be more affected than the same muscles on the other side.
Laboratory:
Elevated Serum Creatine Kinase	Elevation of CPK enzyme in the blood test.  Can be confused with the enzyme released during a heart attack.

Not Everything is Predictable

Those of us living with Kennedy's Disease often like to compare symptoms, CAG Repeats, age of onset, and progression. I believe we do this to feel either better or perhaps worse about ourselves. Unfortunately, not everything is predictable about this gene defect. Allow me to give some examples.

Age of Onset: This could be anywhere from the teens to the 60s. Most often symptoms begin to appear in the 30s and 40s.

CAG Repeats: The number of repeats can be anywhere from the low 40s to the 60s. 34-39 is considered "borderline" and the person might only experience mild symptoms. Researchers now believe the higher the Repeats, the earlier the onset.

Progression and Severity: The earlier the onset, the greater the progression (more severe the condition). This is just a time factor. If onset begins in the 50s for one person and the 30s for another, the 30s person will have experienced 20 years of progression before the 50s person even experiences symptoms.

Symptoms: You would tend to believe that symptoms would be something you could count on, but that is not true either. There is a long list of potential symptoms, but not everyone has the same symptoms, nor do the symptoms appear at the same time in the progression of the disease. Go figure!

What else do we know about the disease?

Pneumonia: This is something that is not kind to us. Almost every doctor encourages us to have the pneumonia vaccination and the booster at age 65. They also recommend the Pneumococcal vaccine today. The flu is something we should also be concerned about because many times it can result in pneumonia. Once again, doctors encourage that you have an annual flu shot.

Exercise: Neurologists have not determined the true value of exercise for those of us with the defect. There is a consensus, however, that exercise if important to our wellbeing. The reason could be as simple as the benefits of endorphins and adrenaline to our general mental, emotional and physical health. Several doctors believe that it is important to continue to stimulate the motor neurons and muscles to keep them healthy as long as possible. And, “muscle memory” is very effective in helping to keep you mobile and upright. Everyone does agree that over-exercising does more harm than good. I can attest to that.

There is also the feeling that exercise and stretching helps "cell inhibition." Cell inhibition is what happens when an activity, such as an exercise, temporarily blocks an unpleasant sensation like a chronic pain. The nerve transmits the pain signal to a cell in the spinal cord that is inhibited by the new "traffic" caused by the stimulus (exercise routine). It is why pinching the cheek blocks the pain from the anesthesia needle in dentistry. Exercise and stretching (working the muscles and joints) produces stimuli for the spinal cord and brain (central nervous system), which is one reason we feel better when we move.

Sedentary Concerns: As the disease progresses, most of us with the defect become less active. We tend to spend more time sitting and do not work our metabolic system. For many of us, "couch potato" is a good phrase that exemplifies our lifestyle as the disease progresses. Weight gain and potential health complications because of the weight, as well as the additional strain on our existing weaker muscles, are always a concern.

Not Everything is KD Related: Just because we have Kennedy's Disease does not mean we are immune to other ailments and health issues. Diabetes, heart and lung disease, kidney failure, as well as many other health concerns are always a possibility as the body ages and based upon hereditary issues.

Continue seeing your regular doctor: Regular physicals and doctor's visits are important for your general health and wellbeing. One man, for example, complained for months about chest pains. He blamed them on Kennedy's Disease and felt he could not do anything about them. The pain finally became severe enough that he saw his doctor. Doctors diagnosed him with having blockage in his arteries.


Please feel free to comment. By taking a moment to share your thoughts you add much to these articles. The articles then become more than just something I said or believe. In addition, by adding a comment, you might just be helping the next reader by sharing your opinion, experience, or a helpful tip.

It Was A Coin Flip...

And, I lost. 

[ This is an update to a 2009 post ]

Spinal Bulbar Muscular Atrophy, aka Kennedy's Disease, is an X-linked disorder. In other words, an X-chromosome is defective (mutated). Kennedy's Disease is caused by a trinucleotide repeat expansion in the androgen receptor gene. This means that the cytosine-adenine-guanine (or CAG) that are normally repeated 10–36 times mutate (expand in our DNA string) to produce a larger repeat size of approximately 40–62.

This CAG sequence is unstable and can change from one generation to the next leading to further expansions. If the person with the defective gene is the father, he cannot pass the gene on to any sons. However, he will pass the defective gene on to any daughters. If the person with the defective gene is the mother, she is a carrier. With a carrier, there is a 50% chance that the defective gene will be passed to any of the offspring.

50% Means One of Two - Right?

Often, there is a misconception that 50% means half of the offspring will have the defective gene. 50% does not mean one out of two chances. It does not work that way. As with any coin flip, heads or tails could come up five, six, or seven times in a row. The 50% means nothing more than over a very large number of flips, half of the time it will be heads.

My mother was a carrier. Her mother had five children and only passed along the defective X-chromosome to my mother. Then, my mother gave birth to ten children (3 girls and 7 boys). Only three of the ten children have the defective gene. I know of other cases where most of the children have the defective gene. The only way to be sure is to take the DNA blood test for Kennedy's Disease.

Now, there is another misconception. Kennedy's Disease does not manifest itself in the same way with everyone. Even if you have the mutated gene, that does not mean that you will have all the symptoms or when the onset of the disease will occur. Not everyone with the defective gene is going to respond the same. Onset could start as early as the teens (this is rare, however), or it could also start in the late sixties. Normally, the onset will occur in the thirties or forties. One person in the family might have most of the symptoms, while another might have only some of the symptoms. The severity of the disorder is also not the same within a family. Researchers currently believe the higher the number of CAG Repeats, the earlier the onset.

So, when my father's sperm fertilized my mother's egg, I lost the coin flip (it came up tails = defective gene). No wonder I have never won the lottery.

No, wait, perhaps it is because I never play the lottery.

Egg-Sperm - https://www.livescience.com/13264

Swallowing markers in spinal and bulbar muscular atrophy

This article was posted on August 17. I have been busy engaged in publishing my latest book, so I did't have a chance to review it before today. Those of us living with Kennedy's Disease often experience problems with swallowing and choking. This article explains the research findings on KD patients and swallowing.You can read the entire article by clicking on the header below.


Swallowing markers in spinal and bulbar muscular atrophy

Swallowing markers in spinal and bulbar muscular atrophy.

Ann Clin Transl Neurol. 2017 Aug;4(8):534-543

Authors: Banno H, Katsuno M, Suzuki K, Tanaka S, Suga N, Hashizume A, Mano T, Araki A, Watanabe H, Fujimoto Y, Yamamoto M, Sobue G

Abstract

OBJECTIVE: We examined the characteristics of dysphagia in spinal and bulbar muscular atrophy, a hereditary neuromuscular disease causing weakness of limb, facial, and oropharyngeal muscles via a videofluoroscopic swallowing study, and investigated the plausibility of using these outcome measures for quantitative analysis.

METHODS: A videofluoroscopic swallowing study was performed on 111 consecutive patients with genetically confirmed spinal and bulbar muscular atrophy and 53 age- and sex-matched healthy controls. Swallowing of 3-mL liquid barium was analyzed by the Logemann’s Videofluorographic Examination of Swallowing worksheet.

RESULTS: Of more than 40 radiographic findings, the most pertinent abnormal findings in patients with spinal and bulbar muscular atrophy, included vallecular residue after swallow (residue just behind the tongue base), nasal penetration, and insufficient tongue movement (P < 0.001 for each) compared with healthy controls. Quantitative analyses showed that pharyngeal residue after initial swallowing, oral residue after initial swallowing, multiple swallowing sessions, and the penetration-aspiration scale were significantly worse in these patients (P ≤ 0.005 for each) than in controls. ...

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There is another article on a 2014 study on tongue pressure in patients with KD. It can be found here:

Tongue pressure as a novel biomarker of spinal and bulbar muscular atrophy.

Image from YouTube video

What is Kennedy's Disease?

Back to the Basics

The Androgen Receptor Gene

The AR gene provides instructions for making a protein called an androgen receptor. Androgens are hormones (such as testosterone) that are important for normal male sexual development before birth and during puberty. Androgen receptors allow the body to respond appropriately to these hormones. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.

The receptors are present in many of the body's tissues, where they attach (bind) to androgens. The resulting androgen-receptor complex then binds to DNA and regulates the activity of androgen-responsive genes. By turning the genes on or off as necessary, the androgen receptor helps direct the development of male sexual characteristics. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.

In one region of the AR gene, a DNA segment known as CAG is repeated multiple times. This CAG segment is called a triplet or trinucleotide repeat. In most people, the number of CAG repeats in the AR gene ranges from fewer than 10 to about 37.

The AR Gene and Spinal Bulbar Muscular Atrophy

Kennedy’s Disease, aka, Spinal Bulbar Muscular Atrophy, results from a particular type of mutation, an expansion of the CAG trinucleotide repeat, in the AR gene. This receptor attaches (binds) to a class of hormones called androgens.

With Kennedy’s Disease, the CAG is abnormally repeated from 38 to more than 60 times causing a disorder of the specialized nerve cells that control muscle movement. Researchers believe that a fragment of the androgen receptor protein containing the CAG repeats accumulates within these cells and interferes with normal cell functions. This buildup leads to the gradual loss of motor neurons, which results in muscle weakness and wasting (atrophy).

People with a higher number of CAG repeats tend to develop signs and symptoms of Kennedy’s Disease at an earlier age. [ FrequentlyAsked Questions about KD ]

Characteristics of Spinal Bulbar Muscular Atrophy

Spinal Bulbar Muscular Atrophy mainly affects males and is characterized by muscle weakness and wasting (atrophy) that usually begins in adulthood and worsens slowly over time. Muscle wasting in the arms and legs results in cramping; leg muscle weakness can also lead to difficulty walking and a tendency to fall.

Certain muscles in the face and throat (bulbar muscles) are also affected, which causes progressive problems with swallowing and speech. Additionally, muscle twitches (fasciculations) are common. Some males with the disorder experience unusual breast development (gynecomastia) and may be unable to father a child (infertile).  [ CommonSymptoms ]

Inheritance Pattern

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females (who have two X chromosomes). [ GeneticChart ]

DNA Test

Fortunately, today there is a DNA test to determine if a person has Kennedy’s Disease. Your doctor can draw some blood and send it to a DNA lab for testing. Test results are normally returned within three-to-six weeks. [ TestDetails ]

Note: Most information provided by the Genetics Home Reference

Can Carriers of Kennedy's Disease experience symptoms?

• Can Kennedy's Disease Carriers experience symptoms? 
• I am a carrier, why do I have severe cramping and difficulty swallowing. 

These type questiona are asked frequently. Researchers believe they know the answer, but since carriers are rarely studied, I am not sure we fully understand why some carriers experience far more severe symptoms and earlier onset. Below is a collection of articles on the subject. If anyone has other sources that might better explain the situation, please let me know.

X-linked dominant inheritance

In X-linked dominant inheritance, when the mother alone is the carrier of a mutated, or defective gene associated with a disease or disorder; she herself will have the disorder. Her children will inherit the disorder as follows:

• Of her daughters and sons: 50% will have the disorder, 50% will be completely unaffected. Children of either sex have an even chance of receiving either of their mother's two X chromosomes, one of which contains the defective gene in question.

When the father alone is the carrier of a defective gene associated with a disease or disorder, he too will have the disorder. His children will inherit the disorder as follows:

• Of his daughters: 100% will have the disorder, since all of his daughters will receive one copy of his single X chromosome.
• Of his sons: none will have the disorder; sons do not receive an X chromosome from their father.

If both parents were carriers of a defective gene associated with a disease or disorder, they would both have the disorder. Their children would inherit the disorder as follows:

• Of their daughters: 100% will have the disorder, since all of the daughters will receive a copy of their father's X chromosome.
• Of the sons: 50% will have the disorder, 50% will be completely unaffected. Sons have an equal chance of receiving either of their mother's X chromosomes.

In such a case, where both parents carry and thus are affected by an X-linked dominant disorder, the chance of a daughter receiving two copies of the X chromosome with the defective gene is 50%, since daughters receive one copy of the X chromosome from both parents. Were this to occur with an X-linked dominant disorder, that daughter would likely experience a more severe form.

• Read the entire article at: Wikipedia    

So, what does happen when a woman has two defective 'X' chomosomes?

Ed Meyertholen provided an explanation in a KDA Forum. Click Here to read more

• This is an abstract of the study Ed mentioned. Click Here for that  

There is another interesting explanation about why symptoms might be more pronounced in some women.  X-inactivation

• Read the entire article at: X-inactivation at Wikipedia    

Back to the Basics

What is Kennedy’s Disease?
 
Kennedy’s Disease (also known as Spinal Bulbar Muscular Atrophy, SBMA, or Kennedy's Syndrome is a rare adult-onset progressive neuro-muscular disease. It is caused by a mutation in the CAG Repeats that affects the function of the androgen receptor. Both the spinal and bulbar neurons are affected causing muscle weakness and wasting (atrophy) throughout the body which is most noticeable in the extremities (legs/arms), it is also noticeable in the face and throat, and can cause speech and swallowing difficulties, along with major muscle cramps as well as other symptoms.


When does a person first start seeing signs of the disease?
 
Symptoms usually beginning to appear in men between the ages of 30 and 50. However, onset has also been reported as early as in the teens and as late as the 60s.


Who gets Kennedy’s Disease?
 
Kennedy's Disease is a genetic disease, passed on from generation to generation in a family. Follow this link for a chart reflecting the genetics of the disorder. Generally males who inherit the defective gene exhibit full symptoms, while females are carriers. Females may also exhibit some symptoms, but normally much later in life.


What are the symptoms?
 
Follow this following link for a list of most of the common symptoms: KD Symptoms 

 
Why haven’t I heard of Kennedy’s Disease before?
 
Kennedy’s Disease is considered a ‘rare disorder’. It is estimated that only 1 in 40,000 individuals worldwide have this condition. However, many people go misdiagnosed or undiagnosed for years.

Is it the forest or the trees?

At least once a year I write an article about this important subject.  And, yesterday, while reading a book, I saw the following quote.

“The only thing potentially worse than not being able to see the forest for the trees is not being able to see the trees because of the forest.”  Anonymous


I loved this quote because it is so true.  We often become blinded with the little knowledge we have and miss important factors concerning our health.  This often happens because we just believe or want to associate most health issues with Kennedy’s Disease.

Twice in the last week I have received emails from men that related symptoms that are not normally associated with Kennedy’s Disease.  I am happy men are asking rather than ignoring the symptoms.

So, let me say it again.  “Do not assume that every health issue is related to Kennedy’s Disease.”  Consult with your family doctor and neurologist whenever a new symptom shows up that is not normally associated with this health condition.

• In 2009 I wrote about this:  Not Everything is Related to KD 
• Again in 2010 I addressed the issue in this article:  Frequently Asked Questions
• And  early this year I again reminded my readers:  Not Every Health Issue is Related to KD 

Each article takes a little different spin on the same subject.  The message can be reduced to seven words …

When in doubt … have it checked out!

Not Every Health Issue is Related to Kennedy’s Disease

Those of us living with Kennedy's Disease have to always be careful that we do not associate (blame) every unusual symptom or health issue on the disease. If it is not listed in the common symptoms for Kennedy's Disease, make certain you check with your GP and neurologist. Just because we have Kennedy's Disease does not mean we are immune to all other health disorders. It is better to play it safe and discuss anything unusual with your doctor.

Examples: A man constantly complained about chest pain and related it to Kennedy's Disease, but later found out he had a heart condition. Another man continually had neck pain and related it to Kennedy's Disease. He finally discussed it with his doctor and after some testing found out it was a pinched nerve.

The key is to have a good open relationship with your neurologist and GP. Sharing general health issues and questions with both doctors will ensure that no medical condition is overlooked or misdiagnosed.