What is Kennedy disease and what causes it to occur?
Kennedy disease — also known as spinal and bulbar muscular atrophy — is a rare, progressive neurodegenerative disease. It principally affects men because it's an X-linked inherited disorder.
DNA sequences are composed of nucleotides linked together by bonds. Some genes contain areas of trinucleotide repeats, which are sets of three nucleotides present in succession. Trinucleotide repeat disorders are a group of human diseases that are a result of an abnormal expansion of these repetitive sequences in a gene that result in dysfunction of that gene. Kennedy disease is one such disease.
Specifically, Kennedy disease results from an excessive number of trinucleotide repeats in the androgen receptor gene, which is located on the X chromosome. The resulting abnormal androgen receptor protein leads to the neurologic and endocrinologic symptoms and signs of Kennedy disease.
What are symptoms of Kennedy disease?
Symptoms can start as early as in the teenage years, or as late as when a person is in their 70s. Patients with Kennedy disease typically live a normal lifespan, but it does cause significant disability in many.
Typical symptoms are slowly progressive weakness and shrinking, or atrophy, of the limb muscles, muscle cramps, tremors, and weakness of the speaking and swallowing muscles. Fasciculations (visible subtle twitching of the muscles under the skin), particularly of the chin muscles, are characteristic.
There are also endocrinologic manifestations that are common, including male infertility, diabetes and gynecomastia, which means enlarged breast tissue in men.
How rare is Kennedy disease, and why is it difficult to diagnose?
Kennedy disease remains relatively rare. It affects about one in 40,000 men in the United States.
It is difficult to make a rapid diagnosis because Kennedy disease shares so many similar symptoms with other neuromuscular diseases. It has a very indolent, linear course, so the diagnosis of Kennedy disease is often missed or mistaken for another condition for many years.
It’s most frequently misdiagnosed as Lou Gehrig's disease, or ALS, because that also causes wasting and weakness in a progressive manner without pain and has some similar features on electromyography, or EMG, testing.
The other thing that makes it difficult to diagnose is that, although it’s an inherited disorder, the clinical features of Kennedy disease are variably expressed in individuals of the same family. Also, family history may be lacking in as many as a quarter to half of patients, so that also makes the diagnosis harder to reach.
To diagnose a patient, we use the patient’s history, physical exam, and then ancillary testing. Genetic testing is now available to confirm if a person has Kennedy disease by demonstrating an excess number of trinucleotide repeats in the androgen receptor gene. So, once you think of it, it’s an easy diagnosis to make because there’s a definitive DNA test.
In what ways is Kennedy disease treated?
There are currently no specific therapies for Kennedy disease. The current treatments really focus on alleviating the symptoms rather than modifying disease progression.
I advise my patients with Kennedy disease to perform light exercise on a regular basis to maintain joint range of motion and promote cardiovascular health.
We concentrate on symptomatic therapies. For tremors, beta blockers are often effective. There are various medications used to help alleviate painful cramps. We make sure that any swallowing difficulties are addressed with proper diet, speech therapy, or a gastrostomy tube if needed. We address mobility issues with physical and occupational therapy to maintain function as long as possible.
We can’t halt the disease’s progression, so we try to give patients every possible chance to function as best possible with the disabilities that Kennedy disease creates.
What further research is needed about Kennedy disease?
There is a lot of research in terms of why the expansion of the trinucleotide repeats leads to dysfunction of the androgen receptor protein, and how we can take advantage of that understanding and develop new treatments.
There are other trinucleotide repeat disorders, such as Huntington’s disease, that have a similar expansion of a trinucleotide repeat, and we still don’t fully understand why that leads either to a gain of function of that gene, which can be toxic, or a loss of function.
Because of the explosion in targeted gene therapy, I would expect that there will be treatments available in the coming decades — hopefully, in my lifetime.
I do believe that we are on the cusp of change for Kennedy disease.
Now that the “Top Chef” contestant Dan Jacobs is talking about his diagnosis, many people are hearing about Kennedy disease for the first time. Why is raising awareness about this disease so important?
It’s not something that’s stressed in medical school training, so there are many physicians who have never even heard of Kennedy disease. Even in neurology, it’s something that we come across rarely. Being aware of it may make it more likely for patients to get an early diagnosis.
A lot of what we do in neurology is give people the comfort of knowing what is happening, even if there are no specific disease-modifying therapies currently available. And that’s very valuable — knowing your diagnosis holds great value.
There’s also a percentage of the population, in general, who live with disabilities every day. Some are visible, some are not. Just making people aware of people, both celebrities and non-celebrities, who live with disabilities leads to greater acceptance of differences among us.
