Teaching About Inherited Human Disorders Through Case Studies

Jack Boroditsky, Hardy DeYoung, and Judith Jones
1994 Woodrow Wilson Biology Institute

This sequence of activities uses a case study method of teaching about inherited human disorders. The goal is to help students understand the genetic basis of various disorders and to participate in the complexities of choosing among the alternatives. The students will use a case study to initiate their investigation into the nature of genes and how altered genes cause changes in cell processes. They will begin to understand how changed cell processes produce overall symptoms in the human organism. Then, the students will find out about the treatments and various alternatives available to individuals and families affected by genetic disorders. Finally, students will make lists of benefits and negatives for each of the choices, including a whole range of issues from the effectiveness of the treatments to family values. Ultimately, students will make their informed decisions.

The following activities follow a logical sequence and may be used that way; however each activity may also be used separately. Inherent in each of these activities is a decision model that is presented in diagram form on the next page and referred to in each of the activities.

Activity 1: Teacher Interactive Presentation

This is a teacher-directed activity that models the behaviors that students would carry out as teams when doing Activity 2. The teacher leads the class in the following process:

  1. teacher presents the case (cystic fibrosis is given only as an example)

  2. teacher asks students to state the dilemma

  3. teacher presents the researched facts about the disorder (see the next activity for a list of the type of information researched)

  4. teacher asks students to restate the dilemma in light of the new information

  5. teacher has students discuss and identify options

  6. as a class, the students list the positives and negatives of each option

  7. students discuss which positives and negatives are directly related to personal values

  8. students vote on the various options according to their understanding of the facts, the positives and negatives of each alternative and their personal values

Activity 2: Students as Genetic Counselors

This is an activity done by teams of students. Students should have a background in Mendelian Genetics, DNA, protein synthesis, and genes. They will be working in teams to prepare a presentation about a specific genetic disorder. The general procedure is outlined below.

  1. The teacher creates and hands out different case descriptions to each team of students; each person in the team is given a copy of that team's case. The cases could involve disorders such as:
    Cystic Fibrosis Marfan's Syndrome Progeria
    Hemophilia Klinefelter's/Turner's Syndromes Tay Sachs
    Down's Syndrome Achondroplasia Thalassemia
    Huntington's Disease PKU-phenylketonuria Ectrodactyly
    Neurofibromatosis Muscular Dystrophy Sickle Cell Anemia

  2. The students follow the procedure outlined in the student activity handout

  3. The teacher helps students locate someone to interview - either someone with a family member affected by the disorder or an expert who knows a great deal about the disorder

  4. The research should include medical and biological sources as well as human interest sources that tell students about real people who have coped with these disorders

  5. The students should include visual aids in their presentations

Activity 3: Using a HyperCard Stack to Present the Report and Vote on Alternatives

These stacks have been prepared so that the student teams can review the issues involved in cystic fibrosis. The stacks contain the same basic information about cystic fibrosis that is contained in the module. Once the layout becomes familiar to students, they may add researched information about other disorders on the supplied blank template. These activities allow students to read and create cards about a variety of genetic disorders and associated issues. Ultimately individuals may register a vote (the second stack will automatically tally student responses) on the alternative choices that are presented. To determine the voting pattern of each class or the daily total, you must open the Voting Stats card. Use the select tool to "frame" the screen and once it is selected, move it to the right to reveal the score. To reset the counter to zero at the start of an activity just click to the right of the number and delete it and replace it with a zero. To cover the counter so that student voting can remain private, you must open the select tool again, surround the screen and move it back over the counter.

HyperCard (2.1) was used to produce this stack on the Macintosh. It will operate on virtually any Macintosh computer with HyperCard installed. If you only have HyperCard Player, be aware that it will limit the creation of new information on the blank templates. HyperCard automatically saves all of your work as you go. Always work with back up copies! None of the original card information has been locked so any changes you make will become permanent! The instructions for the student research are essentially the same as for Activity 2. An example of the cards has been printed in a miniaturized form.

Copies of the stacks are available. Send a cover letter telling where you saw this information, a Macintosh formatted disk, and your self addressed (stamped) mailer to either of the following addresses:
Hardy De Young
Alcoa High School
Faraday Street
Alcoa, TN 37801
Judy Jones
Chapel Hill High School
High School Road
Chapel Hill, NC 27516

Case History A Child with Cystic Fibrosis A Father's Perspective

(adapted from Human Genetics: Concepts and Applications by Ricky Lewis)

Ellen's day began with an inhalation treatment that took a couple of minutes. She used a powerful decongestant mist from an inhaler to loosen the mucus that had settled in her lungs. Then, for half an hour, Ellen was given her postural drainage treatment to accomplish the same end physically. Ellen had to endure eleven different positions, each corresponding to a different section of the lung. Her mother or I pounded on her chest, her back, and her sides, with palms cupped to loosen the mucus. After each position we had to press hard about the lungs with our fingers rolling as we pushed on her...more uncomfortable than the pounding!

Ellen sat up during some positions, but spent others lying flat on our lap. Four of the positions she had to endure nearly upside down with the blood rushing to her head as I pounded away on her chest, rattling her, trying to shake loose the mucus that was trying to take her life away. Ellen complained about the "down" positions, begging not to have them done.

Ellen slowly began to realize that she was singled out for these things and began to grope for the implications. One day when she was four years old, Ellen asked, "I won't have to do therapy when I'm a woman, will I?" It was a difficult question. I knew the score by then! I knew she would not grow up to be a lady unless a cure was found.

Ellen has an older sister who is normal. Their mother and I are considering having another child, but Ellen's illness makes this a troubling dilemma.


  1. How would you answer Ellen's question?
  2. Should Ellen's father tell her the truth about her condition?
  3. What quality of life can Ellen expect?
  4. What are some "short term" issues that Ellen's parents must deal with?
  5. What are some "long term" issues that Ellen's parents should be concerned about?
  6. Should Ellen's parents have another child?

Use the Teacher Background Information sheets to consider the following ideas in answering questions:

  1. What does the word "normal" mean? Who decides?
  2. Who should bear the financial responsibility for genetic conditions?
  3. What are the emotional costs of raising an exceptional child?
  4. What is the child's anticipated quality of life?
  5. What will the quality of life be for family members?
  6. Is there any responsibility not to pollute the "gene pool" any further with defective genes?
  7. How do the risks of having another child with CF compare to the burden of caring for the child?
  8. What are the issues surrounding prenatal diagnosis?

Teacher Background Information

1. Situation (Description)

  • Child with cystic fibrosis (CF). Condition due to an error of metabolism.
  • Condition of the endocrine glands producing mucus, sweat and intestinal secretions which do not function properly,
  • Caused by error in CFTR (Cystic Fibrosis Transmembrane Conductance Regulatory) gene.

2. Interesting Facts

  • Attacks about 1200 Americans annually.
  • 85 groups of scientists in over 20 countries collaborating in search for new CF mutations.
  • 30,000 people under treatment for CF.
  • Cellular defect that underlies CF protects against even deadlier disease - cholera (balanced polymorphism).
  • For further information contact:
  • The Cystic Fibrosis Foundation
  • 6931 Arlington Rd.
  • Bethesda, Maryland 20814
  • (301) 951-4422

3. Clinical Findings

  • Production of large amounts of thick mucus in lungs (congestion, coughing, wheezing)
  • Salty sweat
  • Failure to gain weight
  • Serious respiratory infections (pneumonia)
  • Stubby fingers
  • Foul smelling stools
  • Swelling of the abdomen
  • Terrible pains and stomach troubles
  • Gagging, vomiting, difficulty sleeping
  • Chronic hunger
  • Nasal polyps

4. Complications

  • Inability of intestines to absorb fat due to mucus-plugged pancreas which cannot release digestive enzymes
  • Excess mucus in lungs creates an environment for growth of microorganisms that do not normally inhabit the lungs (sinusitis)
  • Progressive destruction of the lungs
  • Lungs are forced to work extra hard, lose their elasticity, so the breathing is difficult.
  • Reduced fertility in males and females

5. Defect

  • Defective gene codes for an abnormal protein (CFTR).
  • CFTR gene is located in region q-31 of the long arm of chromosome 7.
  • 70% of the mutations involve a 3 base pair deletion (from the 250,000 base pairs in the gene) that causes loss of one amino acid of the 1,480 in the CFTR protein. The protein is still in the membrane, it just doesn't function normally.

6. Pathogenesis

  • Defect in the membrane channels leading from certain glands
  • Chloride ions are trapped inside cells, drawing water into them which thickens the mucus in affected tissues.
  • CFTR works like a 2-way pump, regulating the transport of sodium and chloride across cell membranes. In CF this process fails and the chloride channel stays closed. As a result water is retained in the cell, instead of going out in the dehydrated mucus that causes the condition.

7. Treatment

  • Antibiotic therapy, physical therapy, intake of pancreatic enzymes before each meal to supplement clogged pancreas
  • Inhalation treatment to loosen mucus in lungs
  • Postural drainage treatment to loosen mucus physically. Eleven different positions to catch mucus.
  • Diagnosis early in life before irreversible changes take place
  • Better understanding of "psychosocial" effects of CF on patient and family
  • Diligent self-care with respect to postural drainage and diet control and exercise
  • Support groups to provide important information for parents and patients.

8. Prognosis

  • Shortened life span
  • Today only 10% of affected children survive into their 30's, and a few reach 50.
  • 95% of CF patients die from lung complications and heart failure. 5% die of liver damage.
  • Supplementary O2 may be needed.

9. Detection of Carriers

  • Genetic screening possible but difficult due to the many mutations that cause the condition.
  • Genetic counseling helps couples to make informed decisions before conception.
  • 1 in 20 are carriers.
  • Carriers are asymptomatic
  • Can be detected "indirectly" in the relatives of a CF individual by using DNA-linkage studies.
  • "Direct" PCR DNA testing for the individual is possible.
  • DNA banking (cryopreservation) of a DNA sample from blood, etc. to preserve a family options for testing in the future.

10. Prevention

  • Pre-natal diagnosis for CF gene. Using a combination of biochemical and DNA- linkage tests on amniotic fluid (12-18 weeks), or cells from chorionic villus biopsy (9-11 weeks), or PUBS (Percutaneous Umbilical Blood Sampling) (20 weeks)
  • Screen for CF gene when a couple gets a marriage license.
  • Marry someone who is not a carrier.
  • Artificial insemination with "normal" sperm
  • Adoption
  • In-vitro fertilization of wife's "normal" eggs (predetermined) with husband's sperm.

11. Research Outlook

  • Gene therapy to deliver the protein (virus vector) where the body needs them to prevent the symptoms
  • Mutation detection to develop effective treatment
  • Engineered cells to produce normal CFTR protein using a retro-virus vector
  • Aerosol spray to replace the defective gene in the lung cells. (Genetically engineered virus using CFTR gene is inhaled into the lungs. Theoretically, the gene is replaced and produces normal protein
  • Designer drugs to alter the protein function so it no longer causes the disease
  • Antibody tests for the abnormal protein to speed up diagnosis
  • Gene-probes to detect carriers
  • Heart-Lung transplants
  • Inhalation of Amiloride-used to treat high-blood pressure-thins mucus in lungs making it easier to cough up
  • Using transgenic mice with CF gene to study CF in-vitro
  • Using ATP and UTP which enables the chloride to leave the cells
  • Preimplantation genetic diagnosis probes defective gene(s) in an 8-cell pre-embryo

12. Issues

  • Cost of pancreatic enzymes is high ($20/day)
  • When using antibiotics, one cannot stay out in the sun
  • Antibiotics may cause liver damage
  • Medications run about $10,000 annually
  • Postural drainage treatment sometimes must be administered two or three times a day
  • Who should be screened? The incidence of CF varies in different ethnic groups
  • How do we prevent insurance companies from obtaining screening information and using it to deny health care coverage to people with genetic defects ?
  • At what age should people be screened?
  • Depression and rebellion are common
  • Confusion about test results could lead to stigma
  • Confidential or mandatory
  • Financial and emotional stress on family
  • New therapies are on the horizon
  • Infertility is common; should CF patients have children?
  • Medical risks of pregnancy for a woman with CF
  • Electing or declining pre-natal diagnosis
  • Using donor eggs or sperm from non- carriers
  • Preimplantation diagnosis
  • Limiting family size

13. Related Facts

a) Risk of occurrence
1. autosomal recessive disorder. People who inherit the defective gene from only one parent remain healthy. Those unlucky enough to inherit a defective gene from both parents develop the condition.

b) Age of Detection
1. Reasonable to screen for CF gene when a couple gets a marriage license.
2. "Sweat test" in infancy. Confirmed by an elevated electrolyte test performed at a CF center.
3. Diagnosed in the first five years of life. It is a progressive condition that greatly shortens life expectancy.
4. Diagnosis can be confirmed by DNA analysis

c) Statistics
1. 1 in 2,000 newborns with CF annually (in whites).
2. 1 in 17, 000 black births show CF condition (1/65 are carriers).
3. 1 in 25 American whites carry the gene for a CF causing defect.
4. Very rare in Orientals and American Indians

d) Variations
1. Most common mutation called Delta F-508 deletion which deletes a codon for phenylalanine (accounts for 70% of carriers of northern European descent).
2. Over 100 different CF mutations
3. Severity of the condition is highly variable.
4. 85% of CF patients have both respiratory and digestive problems. 15% have only respiratory symptoms.
5. Although inherited as an autosomal recessive condition, CF is very pleiotropic with variable expression. (Different people display different symptoms and to different degrees.)

Appendix 1

Pedigree Analysis for a Family with Cystic Fibrosis

(not Ellen's family from the case study)

1. Consider III-5, the sister of two affected siblings.

  • what is the probability that she has CF?
  • what is the probability that she is as carrier for the CF gene?
  • what is the probability that she could have an affected child?

2. What pattern of inheritance is shown by this pedigree chart?

3. Determine the genotypes (AA, Aa, or aa) of all of the people in the above pedigree chart. Put a question mark (?) in the symbols of those individuals who could be carriers.

Appendix 2

Recessive Conditions: One in Four Chance

Parents: Carrier Father
x Carrier Mother
Children: AA

Both parents carry a single defective gene (a), but are "normal" phenotype because of the presence of the normal gene (A) which is generally sufficient to protect them. Two defective copies of the gene are required (aa) to produce the condition. Each child has a 1 in 2 (50%) chance of being a carrier like his or her parents and a 1 in 4 chance (25%) of inheriting the disorder.

Appendix 3

Risk of Occurrence

When there is a history of CF, the chance of being a carrier may be increased depending on the degree of relationship to the affected individuals.

Individual Carrier Probability
No known family history of CF1/25 or 4%
Parent of individual with CF1/1 or 100%
Sibling of individual with CF 2/3 or 67%
Niece or nephew with CF1/2 or 50%
Aunt or uncle with CF1/3 or 33%
First cousin with CF1/4 or 25%

To calculate the probability that a child will be affected with CF, multiply the "carrier" probability for each individual by 1/4 (chance both will contribute the CF gene) e.g., if an individual has a sibling with CF and his or her partner has no family history of CF, the chance of having an affected child would be 2/3 x 1/25 x 1/4 = 1/150 chance.


Ball State University, Genethics Workshop, 1992. Cystic Fibrosis Reference Material.

Howard Hughes Medical Institute; 1991, Blazing a Genetic Trail, 2nd Report, 6701 Rockledge Drive, Bethesda, Maryland 20817 pp. 7-32.

Health Sciences Center, University of Manitoba, Dept. of Pediatrics and Child Health, Human Genetics. Report on Human Genetics-Traditional and Non-traditional Inheritance.

Lewis, Ricki, 1994; Human Genetic-Concepts and Applications, Wm. C. Brown Publishers, Dubuque, Iowa pp. 16-18, 217-218, 301-303, 334-335.

Instructions for Genetic Counselor Project


  1. You will work in a team of 2 people.

  2. Each pair of students will receive a different case description; this case will describe people who have a particular genetic disorder in their family.

  3. Each pair of students will follow the procedure described below in order to make thoughtful decisions about the dilemmas suggested by the case descriptions. In the first part, you will assume the role of genetic counselors. In the second part, you will assume the role of the people in a case description from some other team.

Part I: Genetic Counselors:

  • Your team receives a case study.
  • Your team reads the case and writes down an initial description of the dilemma suggested by the case description.
  • Each person in the team gathers more information through library research and an interview with an expert.(Below are details of the research assignment.)
  • Now, you will restate the dilemma based on the research that you have done.
  • . As a team, make a list of all the options for the people in your case. You should have at least 3 alternatives.
  • Begin to list the positive and negative features of each alternative. Your positives and negatives should involve costs, pain, treatment complexities, side effects, family demands, etc. You should NOT talk about religion or other personal values.
4. You and your partner will now make a presentation. You will be role-playing the part of genetic counselors. Another team of students from the class will act as the people in your original case description. They will tell you and the class why they have come to you. You will assume that these people want your expertise as genetic counselors. In preparing your presentation, you should state the dilemma, include the research information listed below, and present the options and the positives and negatives of each option.

5. When you finish the other team will do the following:

  • List the other positives and negatives that have to do with personal values such as religion, family values, and priorities regarding lifestyle, health, money, personal freedom, etc.
  • Weigh all the options and their positives and negatives and rank the options.
  • Select the option that they prefer and explain their choice according to values.


  • Explain the inheritance pattern of the disorder, if known, including the probability of inheritance.
  • Construct a pedigree.
  • Explain where the gene is located (if known) and what it does at the cellular level.
  • Explain the characteristics (symptoms) of the disorder - phenotype.
  • If there is variable expressivity, explain why.
  • Describe actual cases of other individuals with the disorder and what their lives are like.
  • Explain whether the disorder can be detected before birth and whether carriers can be identified.
  • Explain the available treatments and/or preventions.
  • Explain the economic implications (costs) of having the disorder.
  • Any other details that you discover as you conduct your research.

6. The whole class will take notes on your presentation and vote on the options that you present.

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