Information on the following diseases can be found in the Related Disorders section of this report:

• Familial Polyposis
• Peutz-Jeghers Syndrome
• Cronkhite-Canada Disease
• Turcot Syndrome

Symptoms of Gardner syndrome most frequently appear during late childhood or early adulthood. In rare cases, individuals with Gardner syndrome may not exhibit symptoms (asymptomatic). Multiple benign (non-cancerous) growths develop in the colon (colonic adenomas or polyps). These growths are associated with bleeding from the rectum, diarrhea, constipation, abdominal pain, and/or weight loss. Affected individuals have a predisposition to develop malignant (cancerous) tumors in areas outside the colon including thyroid, adrenal, and/or abdominal tumors. Individuals with Gardner syndrome have a much greater risk than the general population of developing colon cancer later in life, especially during middle age.

Bony tumors (osteomas) may affect individuals with Gardner syndrome. Osteomas most frequently occur on the skull and/or jaw, but can affect any bone of the body. The number and size of osteomas varies. Soft tissue tumors (epithelial cysts) may also occur in the skin and fibrous tumors may develop in other parts of the body. Epithelial cysts most commonly affect the legs, face and scalp. In rare cases, individuals with Garner syndrome develop desmoid tumors, benign fibrous tissue tumors that usually affect the abdomen or abdominal wall.

Individuals with Gardner syndrome also have dental abnormalities. Affected individuals have extra teeth (supernumerary) that may cause dental problems such as overcrowding and a misaligned bite. In addition, affected individuals have unerupted teeth, absence of one or more teeth at birth (congenital), and tumors affecting the teeth (odontomas). Individuals with Gardner syndrome may be prone to developing cavities (caries).

Some individuals with Gardner syndrome present with an overgrowth of pigmented tissue in the retina of the eyes (congenital hypertrophy of retinal pigment epithelium or CHRPE). The retina is the nerve-rich membrane that lines the eyes and multiple small patches of brown or black tissue may be seen on the retina.

Individuals with Gardner syndrome may have a greater risk of developing certain types of cancer than the general population. The cancers that are most commonly associated with Gardner syndrome include a malignant liver tumor (hepatoblastoma) and cancer affecting the thyroid or pancreas.
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Gardner syndrome is inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

A gene that causes this disorder, known as the APC gene (for "adenomatous polyposis coli"), has been located on the long arm of chromosome 5 (5q21-22q). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Chromosomes are further subdivided into bands that are numbered.

In individuals with Gardner syndrome, the disorder appears to result from mutation of the APC gene or loss (deletion) of genetic material from chromosome 5q, including the APC gene. Evidence suggests that the APC gene functions as a tumor suppressor gene.
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Gardner syndrome is a rare disorder that affects males and females in equal numbers. This disorder affects approximately one in 15,000 people in the United States. The symptoms usually begin at the age of 20 years but have been known to affect infants and the elderly.

For many years, Gardner syndrome was considered a similar, but separate, disorder from familial adenomatous polyposis. However, most physicians and researchers now consider it a variant of familial adenomatous polyposis that is characterized by multiple polyps in the colon occurring along with symptoms outside the colon (extracolonic).
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Symptoms of the following disorders can be similar to those of Gardner syndrome. Comparisons may be useful for a differential diagnosis:

Familial adenomatous polyposis is a group of rare inherited disorders of the gastrointestinal system. Initially the disorder is characterized by benign growths (adenomatous polyps) in the mucous lining of the gastrointestinal tract. Symptoms may include diarrhea, bleeding from the end portion of the large intestine (rectum), fatigue, abdominal pain, and weight loss. If left untreated, affected individuals usually develop cancer of the colon and/or rectum. Familial adenomatous polyposis is inherited as an autosomal dominant trait. (For more information on this disorder, choose "familial adenomatous polyposis" as your search term in the Rare Disease Database.)

Peutz-Jeghers syndrome (Intestinal Polyposis, Type II) is a rare, inherited gastrointestinal disorder characterized by the development of polyps on the mucous lining of the intestine and dark discolorations on the skin and mucous membranes. Symptoms include nausea, vomiting, and abdominal pain that occurs because of a form of intestinal obstruction (intussusception). Additional symptoms include bleeding from the rectum and dark skin discolorations around the lips, inside the cheeks, and on the arms. Severe rectal bleeding can cause anemia and episodes of recurring, severe abdominal pain. Peutz-Jeghers syndrome is inherited as an autosomal dominant trait. (For more information on this disorder, choose "Peutz-Jeghers" as your search term in the Rare Disease Database.)

Cronkhite-Canada disease (allergic granulomatous angiitis) is an extremely rare gastrointestinal disorder characterized by the formation of polyps in the intestines, the loss of scalp hair (alopecia), abnormally dark discoloration of patches of skin (hyperpigmentation), and the loss of finger and/or toenails. Symptoms may include abdominal pain, cramping, and diarrhea. There is some evidence that this disease may be hereditary. (For more information on this disorder, choose "Cronkhite-Canada" as your search term in the Rare Disease Database.)

Turcot syndrome is an extremely rare inherited disorder characterized by the presence of multiple polyps in the colon and tumors of the central nervous system (e.g., medulloblastoma, glioblastoma, or ependymoma). Symptoms may include diarrhea, bleeding from the rectum, and/or abdominal discomfort. Neurological symptoms vary greatly and depend on the type and location of the central nervous tumors. Additional symptoms may include impaired ability to coordinate movement (ataxia) and/or difficulty speaking. Some researchers believe that Turcot syndrome, like Gardner syndrome, is a variant of familial adenomatous polyposis. Other researchers believe that it is a separate disorder. (For more information on this disorder, choose "Turcot" as your search term in the Rare Disease Database.)

Multiple hamartoma syndrome, also known as Cowden disease, is an extremely rare inherited disorder characterized by the development of many benign, tumor-like growths (hamartomas) affecting multiple organ systems of the body, especially the skin, mucous membranes, breast, and thyroid. Affected individuals also develop characteristic skin abnormalities such as wart-like lesions (verrucous) of the face and limbs; bumps resembling cobblestones on the gums and the mucous lining of the cheeks (buccal mucosa); and/or tiny, benign tumors in the roots of the hair on the face (trichilemmomas). Hamartomas affecting the skin include those made up of connective tissue cells (fibromas), fat cells (lipomas), or small blood vessels just under the surface of the skin (hemangiomas). Other characteristic findings may include neurologic symptoms such as tremors, seizures, impaired coordination of voluntary movement (ataxia), and delayed development of skills that require coordination of movements (psychomotor retardatoin). Individuals with multiple hamartoma syndrome are at a high risk of developing certain malignancies (e.g., dysplastic cerebellar gangliocytoma, breast cancer, primary neuroendocrine skin carcinoma, renal cell adenocarcinoma). In some cases, skeletal abnormalities may be present including abnormal side-to-side (scoliosis), front-to-back (kyphosis), or backward (lordosis) curvature of the spine (scoliosis). Multiple hamartoma syndrome is inherited as an autosomal dominant trait.
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Diagnosis
A diagnosis of Gardner syndrome is made based upon a detailed patient history, a thorough clinical evaluation, identification of characteristic findings (e.g., multiple polyps in the colon, dental abnormalities, and osteomas), and a variety of specialized tests. Because children of an affected parent have a 50 percent risk of developing Gardner syndrome, regular screening via sigmoidoscopy is required until approximately age 35 to 40 to help ensure early detection and prompt, appropriate treatment.

During sigmoidoscopy, a viewing instrument is used to examine the rectum and the last part of the large intestine (sigmoid colon). In addition, in some cases, DNA testing may be available to help detect family members who have inherited certain changes (mutations) of the APC gene, potentially diagnosing the disorder before polyp development. In addition, x-rays of the large intestine may reveal the presence of polyps.

Ophthalmologic evaluation for the presence of congenital hypertrophy of retinal pigment epithelium may be used to help obtain a diagnosis of Gardner syndrome.

Treatment
In Gardner syndrome the major goal of treatment is the prevention or early detection of cancer. Periodic physical examinations should include a test for blood in the stool (occult blood) and direct examination of the walls of the colon with a flexible instrument carrying fiber optics (sigmoidoscopy). These examinations should be done on a regular basis or more often, if the symptoms of diarrhea or rectal bleeding persist. Surgical options include the removal of the colon, and the attachment (anastamosis) of the end of the small intestine to the rectum (ileoproctostomy). This is a less drastic operation than complete removal of the colon and rectum (total colectomy) and may be the surgery of choice for that reason. The rectal area must be monitored for the growth of new polyps. If any appear after surgery, they must be surgically removed. If polyps reappear in great numbers, then the remaining parts of the rectum may have to be surgically removed.

Individuals with Gardner syndrome who have malignant tumors in areas of the body other than the colon may be treated with surgery, radiation, and/or chemotherapy. Treatments vary depending on the size, location, and tumor type. Genetic counseling may be of benefit for individuals with Gardner syndrome and their families. Other treatment is symptomatic and supportive.
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Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 175100; 5/12/00. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?175100.

TEXTBOOKS
Scriver CR, et al. eds The Metabolic Basis of Inherited Disease, 7th ed. New York, NY: McGraw Hill Companies Inc; 1995:646-47.

Larson DE, Editor-in-Chief. Mayo Clinic Family Health Book. 2nd ed. New York, NY: William Morrow and Co., Inc; 1996:787-88.

Beers MH & Berkow R., eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:327.

Yamada T, ed. Textbook of Gastroenterology. 2nd ed. Philadelphia, PA: J. B. Lippincott Company; 1995:1944-54.

JOURNAL ARTICLES
Karazivan M, et al., Familial adenomatous polyposis or Gardner syndrome - review of the literature and presentation of 2 clinical cases. J Can Dent Assoc. 2000;66:26-30.

Neri E, et al., Osteoma of the mandible in Gardner syndrome. Report of a case. Radiol Med (Torino). 1999;98:90-2.

Bonaiti-Pellie C, Genetic risk factors in colorectal cancer. Eur J Cancer Prev. 1999;9:S27-33.

Misiakos EP, et al., Recurrence of desmoid tumor in a multivisceral transplant patent with Gardner's syndrome. Transplantation. 1999;67:1197-99.

Perrier ND, et al., Thyroid cancer in patients with familial adenomatous polyposis. World J Surg. 1998;22:738-42; discussion 743.

Gruner BA, et al., Hepatocellular carcinoma in children associated with Gardner syndrome or familial adenomatous polyposis. J Pediatr Hematol Oncol. 1998;20:274-78.

Hughes-Fulford M, et al., Growth regulation of Gardner's syndrome colorectal cancer cells by NDAIDs. Adv Exp Med Biol. 1997;407:433-41.

Hirata K, et al., Regression of gastric polyps in Gardner's syndrome with use of indomethacin suppositories: a case report. Hepatogastroenterology. 1997;44:918-20.

Hizawa K, et al., Desmoid tumors in familial adenomatous polyposis/Garnder's syndrome. J Clin Gastroenterol. 1997;25:334-7.

Sailer M, et al., Gardner syndrome and thyroid gland carcinoma. Langenbecks Arch Chir. 1997;382:61-3.

Foulkes WD, A tale of four syndromes: familial adenomatous polyposis, Gardner syndrome, attenuated APC and Turcot syndrome. QJM. 1995:88:853-63.