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

Human Gene Editing

I have written posts a few times in the past about CRISPR, a technology that allows the editing of human genes. In my current book I'm writing, the idea of gene editing is an important aspect of creating super-healthy children.

The New York Times published the following article today. As with anything revolutionary in nature, their is controversy surrounding it.

Human Gene Editing Receives Science Panel’s Support

"An influential science advisory group formed by the National Academy of Sciences and the National
Academy of Medicine on Tuesday lent its support to a once-unthinkable proposition: the modification of human embryos to create genetic traits that can be passed down to future generations.

This type of human gene editing has long been seen as an ethical minefield. Researchers fear that the
techniques used to prevent genetic diseases might also be used to enhance intelligence, for example, or to create people physically suited to particular tasks, like serving as soldiers.

The advisory group endorsed only alterations designed to prevent babies from acquiring genes known to cause “serious diseases and disability,” and only when there is no “reasonable alternative.” The report provides an explicit rationale for genetic research that the federal government has avoided supporting until now, although the work is being pursued in countries like Sweden and China.

So-called germ line engineering might allow people to have biological children without fear that they have passed on the genes for diseases like Huntington’s, Tay-Sachs and beta thalassemia, and without discarding embryos carrying the disease-causing mutations, as is often done now. Though such cases are likely to be rare, the report says they should be taken seriously. ..."

Follow the link above to read the rest of the article.

Infant DNA Tests Speed Diagnosis of Rare Diseases

I just read an article in the Health section of the New York Times that was interesting.  The whole article can be read by following the link above, but I have pasted a couple of sections below for your reading.

I believe the most interesting comment was, “… families greatly valued the diagnosis.”  Knowing if often far better than not knowing.  Or, as I have often said, “the best surprise is not surprise at all.”

I can understand the value of this type of testing over the older, more established methods of trial and error, … testing based upon symptoms that show up.

__________________ 

…. The idea behind the test is to take advantage of what is known about disease symptoms to narrow the search for genetic aberrations. And that, said Dr. Joe Gray, an expert in genome analysis at Orego
 
“It’s a big genome,” said Dr. Gray, who was not involved with the study. “How do you know what part of it to search?” 
 
While more research needs to be done before the test is ready for widespread use, he applauded the effort. “If people don’t push the envelope like this, then we won’t get there,” Dr. Gray said. 
 
About one in 20 babies in newborn intensive care units has a genetic disease, and all too often, no one can figure out what it is. Scientists identified the faulty genes for about 3,500 of 7,500 known genetic diseases, said the paper’s authors, adding that about 500 have treatments.

__________________ 

 

… With the new method, a computer program searches for genes based on the baby’s symptoms. And because it focuses only on genes that cause diseases in newborns, it avoids an ethical problem: findings that are unrelated to the problem at hand. In sequencing and analyzing the entire DNA, researchers may discover, for example, aberrations leading to conditions that occur only in adults. Do parents really want to know that their sick baby has a gene that increases the risk of Alzheimer’s disease? 
 
“They did it right, and you rarely hear that from an ethicist,” said Dr. Lainie Friedman Ross, an ethicist and professor of pediatrics at the University of Chicago. Dr. Ross, who praised the researchers for deliberately avoiding such incidental findings, was also not involved with the study.
The method is expensive, though, costing about $13,500. It is not yet covered by insurance. 
 
But Dr. Stephen F. Kingsmore, director of Children’s Mercy’s center for pediatric genomic medicine, expects to show it is cost effective and hopes insurers will pay for it. He noted that each day a baby spends in intensive care costs about $8,000, so any test that reduces that time would quickly pay for itself. A test that reveals a uniformly fatal genetic disease, for example, can allow parents and doctors to know that continuing life support in the hope the baby will improve is futile and only causing suffering. In the meantime, Dr. Kingsmore said, he is hoping a philanthropist will help defray the costs.

__________________ 

 

… The biggest surprise for Dr. Kingsmore, though, was that the families greatly valued having a diagnosis. 
 
When a baby has a mysterious disease, he said, the family often embarks on a terrifying diagnostic odyssey. “Test after test is performed,” he said. “Some tests are invasive; the child is suffering. The child is getting worse and worse — most spend their entire lives in the hospital, and there is no answer.” 
 
Just knowing the answer can be a comfort. “Providing a definitive diagnosis somehow brings closure,” Dr. Kingsmore said. “It is something they can name.”

Genetics Test for ALS now available

The Summer MDA Newsletter had the following article:

“The Athena Diagnostics Division of Quest Diagnostics announced that on April 30, 2012 the first clinically available testing service designed to detect the C9ORF72 repeat expansion mutation that can cause both ALS and frontotemporal dementia (FTD). The C9ORF72 mutation was identified in September 2011 and appears to be the most common known cause of familial ALS, FTD and ALS with FTD. The mutation underlies approximately 40% of familial ALS cases, and also has been found to be responsible for about 8% of sporadic ALS. (Familial ALS refers to situations in which there is more than one known occurrence of ALS in the family; sporadic ALS refers to situations in which there is no known occurrence of the disease in other family members.)


The new genetic test is offered to help speed the diagnosis of ALS. It will be available to clinicians as a standalone test or as part of multigene testing. For testing locations, visit the National Center for Biotechnology Information’s Genetic Testing Registry at http://ncbi.nih.gov/gtr/tests/?term=C1862937.


Those considering genetic testing should speak with their physician. Consultation with a genetic counselor, who can help obtain and interpret the results of genetic testing, is recommended.”


You might ask why this announcement is important to those of us living with Kennedy’s Disease. The most common misdiagnosis for for the mutated CAG triplets repeat gene is ALS. I was one of the people initially misdiagnosed and I know dozens of others that also were misdiagnosed with familial ALS. The initial misdiagnosis of ALS has shattered many lives causing unnecessary stress and often life changing decisions. Having a DNA test that covers approximately 48% of the occurrences of ALS will help rule out that particular disorder when the doctor is unaware of Kennedy’s Disease.