Genetic Disorders

WHAT ARE GENETIC DISORDERS?

A genetic disorder is a disease that is caused by an abnormality in an individual's DNA. Abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or set of chromosomes.

LEVEL 1 DISORDER Single Gene Disorder

These disorders result when a mutation causes the protein product of a single gene to be altered or missing.

LEVEL 2 DISORDER Chromosomal Abnormalities

In these disorders, entire chromosomes, or large segments of them, are missing, duplicated, or otherwise altered.

LEVEL 3 DISORDER Multifactorial Disorder

Multifactorial disorders result from mutations in multiple genes, often coupled with environmental causes.

Some level 3 disorders:

HYPOTHYROIDISM

What is hypothyroidism?

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 produces 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 of its 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 3) Rare and random genetic events in which a mutation is acquired during early development.

What are the symptoms of hypothyroidism?

In babies with the inherited form of hypothyroidism, the condition affects growth and cognitive development. It may cause mental retardation, delayed puberty, stunted growth, and ataxia (inability to coordinate 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 produce, and for how long they have had the disorder.

When the body is deprived of thyroid hormone, the pituitary gland works overtime, producing extra thyroid-stimulating hormone (TSH). This glut of TSH may enlarge the thyroid into a condition called a goiter.

COLON CANCER

What is colon cancer?

Cells normally grow and divide only when they are needed to keep our bodies functioni properly. But sometimes, the mechanisms that regulate cell growth stop working and ce divide out of control to form tumors. This is called cancer. When cancer develops in the ce lining the colon (the first part of the large intestine), it is called colon cancer. People who have a history of colon cancer in their family are at greater risk of getting t disease themselves. The risk increases when a relative has had the disease before age 5 These families are considered high-risk, because they may have inherited one of two ra genetic conditions: FAP (familial adenomatous polyposis) or HNPCC (hereditary non-polypos colon cancer). FAP is caused by mutations of the APC (adenomatous polyposis coli) gene on chromosome APC is a tumor suppressor gene, which means that it prevents uncontrolled cell growth. Peop who inherit a mutated form of this gene develop growths called polyps in their colon. By age 1 they may have hundreds of these polyps. Polyps are not cancerous at first, but if they are treated, they will develop into colon cancer. HNPCC (also called Lynch syndrome) is caused by mutations in one of several genes that damaged DNA. People who inherit one of these mutations have a much greater risk 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 run a 50 percent risk of inheriting the mutated gene. Usually when a person inherits a defective gene it does not necessarily mean he or she will 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 before. HNPCC also increases a person's risk of developing other cancers, including ovarian, stomach, brain, and liver.

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? When 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 special 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 up 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.