Huntington Disease

Inheritance	autosomal dominant
Occurrence	1 in 20,000 (approximately 30,000 Americans have HD and 150,000 are at riskof inheriting HD from a parent)
Description	degenerative brain disorder which results in loss of both mental and physical abilities-- adult onset generally
Location of gene and cause of HD	found on chromosome 4-- it is the trinucleotide CAG repeated over and over again. Those with HD will most often have at least 40 of these repeats. Individuals with fewer than 30 repeats will not develop HD.
Testing for HD	is available to individuals through a blood sample

Pedigree Building

Students will need to know the symbols associated with pedigrees (male, female, married, affected). Some basic activities would be appropriate. Have the students draw a pedigree of their family following a simple trait such as tongue rolling, or attached ear lobes. Color in the symbols for those who have attached earlobes or can roll their tongue. Talk about how simple pedigrees contain a lot of information.

Introduce the students to Huntington Disease. (Use the information given in the table above).

Woody Guthrie was a renowned folk singer, most popular today for the song, "This Land Is Your Land." He died in 1967 from Huntington disease. Here is a link to the Woody Guthrie home page. There are many photos of him throughout his life as well as a brief biography. Have the students read the biography and make a pedigree of his family tracing Huntington Disease. This will encourage reading and comprehension as well as provide the necessary information. Students will have to be clever with his pedigree since Woody Guthrie had three wives and children with each wife. When the students have completed his pedigree, it may be appropriate to discuss autosomal dominant inheritance, particularly the information that each child of an affected parent has a 50% chance of inheriting the disease. This is best shown with Punnett squares. Here are some questions to ask.

(3) If neither of your parents has Huntington Disease, what is the probability you will get the disease? 0%, except by fresh mutation

Below is one version of a completed pedigree students should be able to compose after reading Woody Guthrie's biography.

To Test or Not To Test?

Students will need to understand the nature of Huntington Disease. (The previous activity on pedigree building would be a good introduction).

Below are three case studies. Have the class work in groups of two or three. Working in groups will (hopefully) allow for more issues to be brought up and discussed as well as provide the opportunity for students to disagree with other students' positions in an intellectual manner. The groups may discuss each case, or different groups may discuss different cases.

(1) Caren is 41 years old and married with three children. Her mother died from Huntington Disease at the age of 61. Caren never wanted to undergo any form of testing. She wanted to go through life pretending she could never get Huntington Disease. She had always wanted children and felt that if she found out she had Huntington Disease she would never be comfortable knowing she could be passing the disease on to her children. She has lived her life ignoring the issue. Now, however, she is can hardly stand not knowing. Every day she wonders if this will be the day she starts having symptoms. Every time she has a slight muscle spasm she wonders if this is the beginning of the long decline. The uneasiness has caused her to contemplate suicide. In many ways she wishes she had the courage to undergo the test for heterozygosity because if it came back negative she could finally rid herself of all her fears; however, if the test were to come back positive she is not sure she could go on knowing that inevitably she would die such a tragic death. Even worse would be the guilt she would feel knowing that since she has Huntington disease, each of her children now has a 50% chance of also being affected. As Caren's counselor, what would you recommend?

(2) When James was two years old his mother died at the age of 24 in a car accident. James was her only child. When he was eighteen, his father told him that his mother could have had Huntington Disease. Her father had died from it. James' mother had a 50% chance of having Huntington Disease, and, if she had it, James has a 50% chance of having it as well. James is trying to decide whether to be tested. He is engaged and would like to tell his fiance and know his genotype before they have any children. He is a little apprehensive because he does not know how his fiance will react. What would you counsel James to do?

(3) Maria is watching her two older siblings slowly degenerate from Huntington Disease. She wants to get tested but does not know if she could handle knowing for certain. She already feels guilty being younger and not having the disease yet. In many ways she hopes she does have the Huntington Disease allele, because if she does not she wonders how she can go through life having to constantly ask, "Why not me?" "What did they ever do to deserve this?" She would have to live the rest of her life wondering why this happened to her siblings but not to her. Perhaps it would be easier never knowing for certain and living each day wondering if tomorrow it will happen to her as well. How would you advise Maria?

Nancy Wexler

Nancy Wexler, Ph.D. has dedicated her life's work to advance our understanding of hereditary diseases. Specifically she has focused her work on Huntington Disease. She has a personal interest because her mother died of Huntington Disease. Dr. Wexler has a fifty-fifty chance of also inheriting the degenerative disease. Her work was important in developing the test which can identify who carries the allele (gene) that causes Huntington Disease She is president of the Hereditary Disease Foundation and spends a significant amount of her time with a Venezuelan community where Huntington Disease is quite prevalent. With her research and efforts, the hope is someday to eradicate this disease.