Kennedy’s disease
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Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is a rare adult-onset form of spinal muscular atrophy (SMA), first described by neurologist William Kennedy in a 1968 report. It is a progressive neurodegenerative disorder mostly affecting men.
The symptoms usually begin in adulthood, between the ages of 20 and 40, but some research suggests that symptoms can start as early as childhood. Kennedy’s disease is known to cause muscle weakness and atrophy in the face and throat, as well as the limbs. With treatment, someone with Kennedy’s disease can have a near-normal life expectancy.
Kennedy’s disease is also known as Kennedy’s syndrome and X-linked spinal and bulbar muscular atrophy.
Other forms of SMA, which are caused by mutations in the SMN1 gene, are divided into five main types — 0, 1, 2, 3, and 4. Kennedy’s disease is one of the rare SMA types. Other rare types include lower extremity dominant (SMA-LED), SMARD1, Finkel type, and X-linked infantile SMA.
What causes Kennedy’s disease?
Kennedy’s disease is a rare, X chromosome-linked, progressive neuromuscular disorder that is associated with a defect in the androgen receptor (AR) gene, which provides instructions for making the androgen receptor protein.
The AR gene has a DNA segment called CAG trinucleotide repeat (or CAG triplet) that is repeated several times. In most people, the number of CAG repeats varies from about 10 to up to 36; but in people with Kennedy’s disease, the number of repeats is greater — being repeated at least 38 times. This abnormal expansion of CAG repeats in the AR gene results in the production of an abnormally large androgen receptor protein that has an altered structure.
It is not clear how abnormal androgen receptor proteins damage motor neurons — specialized nerve cells that control muscle movement, and which are affected in Kennedy’s disease. It is thought that the abnormal protein may build up inside the cells until it disrupts their normal function and triggers their death.
It is estimated that Kennedy’s disease affects 1 in 40,000 people worldwide.
How is Kennedy’s disease inherited?
As an X-linked disorder, Kennedy’s disease mainly affects men.
Genetically, everyone typically has two copies of every chromosome apart from the sex chromosomes. Females have two X chromosomes, while males have one X and one Y chromosome.
The affected AR gene in Kennedy’s disease is located on the X chromosome. This means that if a woman carries a defective AR gene on one of her X chromosomes, she most likely will not show any symptoms because the gene on the other X chromosome can compensate for the defect.
However, there is a 50% risk of passing the defective gene to their child — a 50% risk of having a son with Kennedy’s disease, and a 50% risk of having a daughter who, like herself, also is a carrier of the mutated gene. This is why the disease affects more men than women.
Due to the way Kennedy’s disease is inherited, men cannot pass X-linked genes to their male children, but will pass it to their female children.
What are the symptoms of Kennedy’s disease?
Kennedy’s disease symptoms are mainly associated with progressive muscle weakness and wasting in the arms and legs. Some of the symptoms include:
- reduced tendon reflexes
- frequent cramps
- hand tremors and shakiness in other limbs
- fatigue.
This commonly results in:
- leg weakness, leading to difficulty walking
- increased risk of falls.
In later stages of the disease, some patients may need to use a wheelchair to move around.
Kennedy’s disease also can cause weakness in the muscles of the face and tongue (bulbar muscles), resulting in difficulty speaking or swallowing. However, these symptoms tend to develop later in the course of the disease. This can include:
- bulbar difficulties, such as chewing, swallowing, talking and other functions of the throat
- coughing and choking, including inhaling small bits of food.
As the mutated gene affects the body’s response to androgens — which are hormones such as testosterone involved in male sexual development — the disease can have other symptoms including:
- infertility
- testicular atrophy (shrinkage)
- a low sperm count
- enlarged breasts
- erectile dysfunction.
Some studies have suggested that people with Kennedy’s disease are more likely to be affected by metabolic disorders, including insulin resistance and fatty liver disease, which can lead to heart disease and serious liver damage.
Kennedy’s disease symptoms vs. ALS
Symptoms of Kennedy’s disease are very similar to that of amyotrophic lateral sclerosis (ALS), a more well-known motor neuron disease, sometimes leading to people receiving an incorrect diagnosis.
In its earlier stages, ALS causes symptoms such as stiff muscles, muscle twitching, and a gradual loss of muscle strength. As the disease progresses, muscles become paralyzed, and patients experience difficulty in speaking, swallowing, and eventually, breathing.
Compared to ALS, Kennedy’s disease progresses much more slowly. The differentiation between the two conditions is usually made based on the person’s medical history and physical examination.
How is Kennedy’s disease diagnosed?
Once Kennedy’s disease is suspected, a blood test can be done to look at creatine kinase levels, as high levels may indicate muscle injury or disease. People with Kennedy’s disease often have elevated levels of this enzyme.
Definite diagnosis of Kennedy’s disease is done by a blood test to detect the CAG triplet repeat expansion in the AR gene. In general, Kennedy’s disease is associated with more than 38 CAG repeats being present in this gene.
The CAG triplet repeat test can diagnose both affected men and women who are carriers.
Kennedy’s disease is frequently misdiagnosed, as the initial symptoms can mimic many other disorders. Moreover, as the disease is rare, it may not be the first suspected cause of the symptoms. Genetic testing will help rule out ALS.
What treatment options are available for Kennedy’s disease?
Currently, there is no known cure for Kennedy’s disease. Treatment is symptomatic and supportive to help people living with SMA.
Treatment includes:
- physical therapy, to maintain strength and flexibility in muscles, and to train how to exercise
- speech therapy, for those experiencing weakness in the facial and throat muscles
- occupational therapy, which focuses on adjustments that help people manage their everyday lives
- medications to decrease tremors and cramps.
The benefits of exercise for people with all types of spinal muscular atrophy include slowing of muscle weakness, improved range of motion, improved motor function, prevented contractures, improved posture and flexibility, and better mental health.
Supportive therapies for SBMA include the use of specialized equipment to assist in symptom management. This can include:
- adaptive strollers
- wheelchairs, walkers, and standers
- bath chairs and feeding chairs.
Certain equipment can directly reduce symptoms such as difficulty swallowing. These can include:
- feeding tubes
- respiratory aids such as BiPAP machines and cough assist machines.
There is no available gene therapy for Kennedy’s disease at this point in time.
What is the life expectancy for people with Kennedy’s disease?
Due to the late-onset nature of Kennedy’s disease, life expectancy is near normal, affected by the slow progression of the disease. This differs from other forms of spinal muscular atrophy, where an early diagnosis is important and can have a positive effect on life expectancy.
SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Kennedy's disease
Kennedy’s disease is caused by mutations in the AR gene, located on the X chromosome, and is more common in men than women, with symptoms usually starting between ages 20 and 40. The disease’s hallmark is progressive weakness and atrophy of the muscles closer to the trunk and those of the mouth and throat. This form of spinal muscular atrophy can cause difficulty breathing, but most patients have a normal life expectancy.
It is rare for a woman to show symptoms of Kennedy’s disease, however, women can be carriers of the gene mutation that causes the disease and pass it onto their children.
At this point in time, there is no cure for Kennedy’s disease. Treatment is supportive in order to maintain quality of life.
Doctors will perform a physical exam followed by blood tests. These blood tests look for elevated levels of creatine kinase, as people with Kennedy’s disease often have elevated levels of this enzyme, and to detect the CAG triplet repeat expansion in the AR gene. In general, Kennedy’s disease is associated with more than 38 CAG repeats present in the AR gene. The CAG triplet repeat test can diagnose both affected men and women who are carriers.
Yes, adult men can develop Kennedy’s disease, usually between the ages of 20 and 40 or later. Women can be carriers of the genetic mutation that causes the disease, but usually do not develop symptoms.
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