Examples of Multifactorial Disorders

These disorders involve variations in multiple genes, often coupled with environmental causes.

Alzheimers Disease

What is Alzheimer's disease?

Alzheimer's is a disease that causes dementia, or loss of brain function. It affects the parts of the brain that are important for memory, thought, and language.

The brain of a person with Alzheimer's contains abnormal clumps of cellular debris and protein (plaques) and collapsed microtubules (support structures inside the cell). Microtubule collapse is caused by a malfunctioning protein called tau, which normally stabalizes the microtubules. In Alzheimer's patients, tau proteins instead cluster together to form disabling plaques and tangles. These plaques and tangles damage the healthy cells around them, leading to cell death. The brain also produces smaller amounts of neurotransmitters (acetylcholine, serotonin, and norepinephrine), chemicals that allow nerve cells to talk to one another.

Alzheimers Chromosome

The most common form of the disease, which strikes after age 65, is linked to the apolipoprotein E (apoE) gene on chromosome 19. Scientists don't know how apoE4 increases the risk of developing Alzheimer's. They do know that everyone has apoE, which comes in three forms.

One of the forms (apoE4) increases a person's risk of developing Alzheimer's. The other two forms seem to protect against the disease. While people who inherit the apoE4 form of the gene are at increased risk for the disease, they will not necessarily develop it.

Mutations in genes found on chromosomes 1, 14, and 21 are linked to rarer forms of the disease, which strike earlier in life.

Alzheimers Brain Plaques Tangle

How do people get Alzheimer's disease?

Scientists don't know exactly how people develop Alzheimer's, but they believe it is caused by a combination of genes and environmental factors. In other words, it is a multifactorial disorder.

The early-onset forms of Alzheimer's are inherited in an autosomal dominant pattern, which means that only one parent has to pass down a defective copy of the gene for their child to develop the disorder.

What are the symptoms of Alzheimer's disease?

Because Alzheimer's destroys brain cells, people who have the disorder slowly lose their ability to think clearly. At first, they may forget words or names, or have trouble finding things. As the disorder worsens, they may forget how to do simple tasks, such as walking to a friend's house or brushing their hair. Some people with Alzheimer's also feel nervous or sad.

Autosomal Dominant

How do doctors diagnose Alzheimer's disease?

There is no single test for Alzheimer's. Doctors use several different tests to check a patient's memory, language skills, and problem solving abilities. These tests don't diagnose Alzheimer's, but they can rule out other disorders that have similar symptoms.

How is Alzheimer's disease treated?

There is no cure for Alzheimer's, but a few medicines can slow its symptoms. A drug called Aricept increases the amount of the neurotransmitter acetylcholine in the brain. Another medicine, Namenda, protects brain cells from a chemical called glutamate, which can damage nerve cells. Doctors may also give their Alzheimer's patients antidepressants or anti-anxiety medicines to ease some of their symptoms.

People with Alzheimer's often need a caregiver—someone to help them do the things they were once able to do themselves.

Interesting facts about Alzheimer's disease

Alzheimer's was named after the German doctor, Alois Alzheimer, who first named the disorder in 1906.

The older a person gets, the higher his or her risk of getting Alzheimer's. Only about 1 or 2 people out of 100 have Alzheimer's at age 65; whereas, one out of every five people has the disorder by age 80.

As many as 4 million Americans have Alzheimer's disease.

Breast Ovarian Cancer

What is breast cancer and ovarian cancer?

Cells normally grow and divide just enough to grow or to replace damaged tissue. But sometimes the mechanisms that regulate cell growth stop working and cells divide out of control. This out-of-control growth is called cancer. Cancer that develops in breast or ovarian tissue is called breast or ovarian cancer, respectively.

BRCA Chromosome

Most people who develop breast or ovarian cancer have no history of the disease in their family. In fact, only 5 to 10 percent of all breast and ovarian cancers are caused by inherited genetic factors. These rare cases typically result from inherited mutations in either the BRCA1 or BRCA2 gene.

BRCA1 and BRCA2 are called tumor suppressor genes, because they control cell growth. BRCA1 is located on chromosome 17, and BRCA2 on chromosome 13. Scientists believe BRCA1 and BRCA2 work by fixing damaged or broken DNA. Women who inherit a mutated copy of the BRCA1 or BRCA2 gene accumulate broken and deformed chromosomes, and therefore have a greater chance of accumulating mutations that will lead to uncontrolled cell growth and cancer. Men who inherit the defective genes are also more likely to develop breast and/or prostrate cancer. (Yes, men can get breast cancer.)


How do people get breast or ovarian cancer?

High-risk families include those whose members carry a mutation in either the BRCA1 or BRCA2 gene. The mutated BRCA1 and BRCA2 genes are inherited in an autosomal dominant pattern. A child needs to inherit just one copy of the mutated gene to have an increased cancer risk. Children who have a parent with a BRCA1 or BRCA2 mutation have a 1 in 2 chance of inheriting the mutation.

Just because a person inherits the defective gene does not mean he or she will develop cancer, but inheritance greatly increases the risk. Out of every 100 women who inherit a mutated BRCA1 or BRCA2 gene, as many as 60 will develop breast cancer by age 50; by age 70, approximately 80 will develop breast cancer.

How do doctors test for BRCA1 and BRCA2 mutations?

A person with a strong family history of breast or ovarian cancer is a candidate for genetic screening. By analyzing a sample of the patient's blood, doctors can identify whether the person has inherited a BRCA1 or BRCA2 mutation. The test cannot tell if or when the person will develop breast or ovarian cancer; it can only tell if he or she is at risk because of the faulty gene.

Autosomal Dominant

What can a woman do if she inherits these mutations?

Some women who discover that they've inherited a mutated BRCA1 or BRCA2 gene undergo special treatments to protect themselves from breast and ovarian cancer. They can start having mammograms at a younger age to screen for abnormal cell growth in the breasts (most women start having mammograms at age 40).

They may choose to have their breasts and/or ovaries removed, even before cancer begins. And they may take the medicine tamoxifen, which is believed to protect against breast cancer.

Interesting facts about breast and ovarian cancer

The progression from a benign to a malignant cancer typically requires multiple mutations that allow cells to acquire new and abnormal characteristics, such as an increased growth rate, inability to adhere or stick to neighboring cells, propensity to migrate to other places in the body, etc. Genes involved in the repair of DNA damage (such as BRCA1 and BRCA2) are often associated with cancer. This is because they allow mutations to accumulate at a much faster rate.

Usually, people inherit one of several hundred different mutations of the BRCA1 and BRCA2 genes. But for some reason, Eastern European (Ashkenazi) Jews seem to inherit only three of these different mutations. Ashkenazi Jews are also 10 times more likely to have mutations in the BRCA1 and BRCA2 genes than any other ethnic group.

Colon Cancer

What is colon cancer?

Cells normally grow and divide just enough to grow or to replace damaged tissue. But sometimes, the mechanisms that regulate cell growth stop working and cells divide out of control. This out-of-control growth is called cancer. Cancer that develops in the cells lining the colon (the first part of the large intestine), is called colon cancer.

People who have a history of colon cancer in their family are at greater risk of getting the disease themselves. The risk increases when a relative has had the disease before age 50. People in these families are considered high-risk, because they may have inherited one of two rare genetic conditions: FAP (familial adenomatous polyposis) or HNPCC (hereditary non-polyposis colon cancer).

Colon Cancer Gene

FAP is caused by mutations of the APC (adenomatous polyposis coli) gene on chromosome 5. APC is a tumor suppressor gene, which means that it controls cell growth. People who inherit a mutated form of this gene develop growths called polyps in their colon. By age 15, they may have hundreds of these polyps. Polyps are not cancerous at first, but if they aren't treated, they will develop into colon cancer.

HNPCC (also called Lynch syndrome) is caused by mutations in one of several genes that fix damaged DNA. People who inherit one of these mutations have a much greater risk of accumulating mutations that will lead to uncontrolled cell growth and cancer.


How do people get colon cancer?

FAP and HNPCC are both inherited in an autosomal dominant pattern. If a parent has FAP or HNPCC, his or her children have a 1 in 2 chance of inheriting the mutated gene. A person who inherits a defective gene will not necessarily develop a malignant cancer. However, the APC gene strikingly predisposes one to colon cancer. People who inherit one bad copy of the APC gene are practically guaranteed to develop colon cancer by age 40. Similarly, people who inherit one bad copy of a gene associated with HNPCC have an 80 percent chance of getting colon cancer. HNPCC also increases a person's risk of developing other cancers, including ovarian, stomach, brain, and liver.

Autosomal Dominant

What are the symptoms of colon cancer?


Colon cancer affects the stomach and bowels. Common symptoms include diarrhea or constipation, blood in the stool, vomiting, bloating, cramps, and unexplained weight loss.

How do doctors diagnose colon cancer?

Even before a patient shows symptoms of colon cancer, his or her doctor can screen for the disease using one of several tests:

  • Fecal Occult Blood Test (FOBT) - Colon cancer can sometimes cause tiny dots of blood, too small for the eye to see, in the feces. The FOBT test uses a chemical to check the patient's stool sample for these traces of blood.
  • Flexible-Sigmoidoscopy - Using a thin flexible tube called a simoidoscope, the doctor looks inside the patient's colon for growths called polyps.
  • Double Contrast Barium Enema (DCBA) - A silvery-white metallic substance called barium is inserted into the patient's colon through the rectum. The barium outlines the patient's colon on an x-ray screen.
  • Colonoscopy - Using a thin instrument called a colonoscope, the doctor looks inside the patient's colon. During the procedure, the doctor removes pieces of tissue (called a biopsy) to test them for cancer. If the doctor finds any polyps, he or she can also remove them. A newer method, called virtual colonoscopy, looks at the colon without going into the body, with an MRI or CT scan.
  • DNA-Based stool test - This test examines DNA taken from a patient's stool sample to look for genetic defects associated with colon cancer.

How is colon cancer treated?

Colon cancer is very treatable. In fact, about 90 percent of patients survive the disease after treatment. First, doctors stage the disease to see how far it has progressed. If the cancer has not spread to other tissues of the body, it can be treated with chemicals (chemotherapy) or radiation (powerful x-rays) to kill all rapidly dividing cells in the body, including cancer cells or surgery to remove the polyps and/or cancerous part of the colon

Interesting facts about colon cancer

People who have FAP can develop hundreds and even thousands of polyps, whereas people with HNPCC develop relatively few.

The progression from a benign to a malignant cancer typically requires multiple mutations that allow cells to acquire new and abnormal characteristics, such as an increased growth rate, inability to adhere or stick to neighboring cells, and propensity to migrate to other places in the body. At least seven mutations are required to produce a malignant colon tumor.

Inherited cancers often provide clues about the genes mutated in noninherited (sporadic) cancers. For example, mutations in the APC gene are found not only in FAP tumors but in 85% of all sporadic colon tumors as well.


What is hypothyroidism?

Hypothyroidism Chromosome The thyroid is the largest endocrine gland in the body. It sits just below the larynx (voice box) and wraps around the trachea (windpipe). The thyroid gland produces thyroid hormone, which helps the body grow and develop. It also plays an important role in the body's metabolism (the processes in the body that use energy, such as eating, breathing, and regulating heat).

Hypothyroidism (or underactive thyroid) is a common condition in which the thyroid gland makes too little thyroid hormone. About 1 in 5,000 babies is born with congenital hypothyroidism, in which the thyroid fails to grow normally and cannot produce enough hormone. There is no known cause for most cases of congenital hypothyroidism. But about 10 to 20 percent of the time, the condition is caused by an inherited defect that alters the production of thyroid hormone.

The most common inherited form of hypothyroidism is a defect of the TPO (thyroid peroxidase) gene on chromosome 2. This gene plays an important role in thyroid hormone production.

How do people get hypothyroidism?

Hypothyroidism may be caused by (1) an autoimmune disease that attacks the thyroid gland, (2) surgery or radiation to treat thyroid cancer and other conditions, or (3) rare and random genetic events in which a mutation is acquired during early embryonic development.

Autosomal Recessive

What are the symptoms of hypothyroidism?

In babies with the inherited form of hypothyroidism, the condition affects growth and cognitive development. It may cause intellectual disability, delayed puberty, stunted growth, and ataxia (uncoordinated muscle movements).

In adults, hypothyroidism slows the body's metabolism, making the patient feel mentally and physically sluggish. Symptoms may include weakness, fatigue, muscle aches, mood swings, hair loss, memory loss, or slow speech. A person's symptoms will depend upon how little thyroid hormone they make, and for how long they have had the disorder.

When the body has too little thyroid hormone, the pituitary gland works overtime, making extra thyroid-stimulating hormone (TSH). Having too much TSH may enlarge the thyroid, forming a goiter.


How do doctors diagnose hypothyroidism?

Babies are normally screened for hypothyroidism 24 hours after birth. A tiny sample of blood taken from the baby's heel is tested for low thyroid hormone levels or high thyroid-stimulating hormone (TSH) levels.

How is hypothyroidism treated?

Hypothyroidism is treated with hormone replacement therapy: people with hypothyroidism must take a synthetic form of thyroid hormone every day to reduce their symptoms. When treatment is started right away, babies develop normally.

  • Funding

    Funding provided by grant 51006109 from the Howard Hughes Medical Institute, Precollege Science Education Initiative for Biomedical Research.