Gardner syndrome
Gardner syndrome is a rare genetic disorder that falls under the category of familial adenomatous polyposis (FAP). It is characterized by the development of numerous polyps in the colon, as well as abnormal tissue growth in various organs, which may include skull tumors, cysts, and additional dental anomalies. Individuals with Gardner syndrome face a significantly heightened risk of developing several types of cancers, particularly colorectal cancer, which can arise from colon polyps that have a near 100% chance of becoming malignant. The condition is linked to mutations in the APC gene, and while it is often hereditary, about 20% of cases arise from spontaneous gene mutations.
Symptoms can vary widely, but common issues include gastrointestinal problems such as rectal bleeding and abdominal pain, as well as skin cysts that may become inflamed. Screening and early diagnosis are crucial, often involving genetic testing for the APC mutation alongside various imaging studies to monitor for polyps and tumors. Treatment typically requires surgical intervention to remove polyps and any problematic tumors, and ongoing management may involve medications like sulindac to reduce cancer risk. Despite the challenges posed by Gardner syndrome, proactive medical care can help improve outcomes for those affected.
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Gardner syndrome
DEFINITION: Gardner syndrome is a rare, genetically linked disorder that is classified as a variant form of familial adenomatous polyposis (FAP), a group of disorders most commonly identified by the growth of numerous polyps in the large intestine or colon. In Gardner syndrome, large amounts of tissue form in multiple organs. As with FAP, this includes colon polyps as well as skull tumors, cysts and fibrous tumors in the skin, extra teeth, and a congenital eye condition. Gardner syndrome significantly increases an affected person’s risk of developing colorectal cancer, small bowel cancer, pancreatic cancer, and papillary thyroid cancer. Early diagnosis of the disorder is essential, as colon polyps resulting from Gardner syndrome have a nearly 100 percent chance of becoming cancerous, according to the American Cancer Society (2024).
ALSO KNOWN AS: Gardner’s syndrome, familial adenomatous polyposis, familial polyposis coli, hereditary adenomatosis of the colon and rectum, bone tumor-epidermoid cyst-polyposis
RELATED CONDITIONS:Colon and rectal polyps, colorectal cancer
Risk factors: Gardner syndrome is genetically linked, meaning that it is associated with a defect, or mutation, in one or more genes. A person with family members with the disease or with the defective gene is at high risk of developing this disorder. It is estimated that 20 percent of patients do not have a family history of FAP, which indicates a spontaneous mutation of the gene.
Etiology and the disease process: Normally, during conception, the body receives two copies of every gene, one each from the mother and the father. It takes only one copy of a defective gene, from either the mother or father, for a person to be affected by Gardner syndrome. This disease is caused by a mutation in the gene called APC (adenomatous polyposis coli). The defective APC gene participates in (and may even initiate) the adenoma-to-carcinoma sequence, which allows cells in the colon to increase in number and causes the lining of the colon to thicken. Most people who receive this defective gene develop the disease. Although the way Gardner syndrome develops varies from person to person, it always presents a high risk of developing polyps, tumors, and cancer, especially in the colon. Other physical changes that occur (with their percentage of risk when known) include congenital hypertrophy of the retinal pigmented epithelium, epidermoid cysts (50 to 60 percent), gastric polyps (12 percent), thyroid cancer, desmoids (8.6 percent), dental abnormalities (30 percent), hepatoblastoma, and bone tumors.
Incidence: Gardner syndrome is considered to be rare, with only 1 in 7,000 to 1 in 30,000 births, whereas the incidence of FAP is 1 case per 5,000 and 1 per 31,000 people, according to the NIH. An increased risk for the development of thyroid cancer and desmoid tumors has been noted in women with Gardner syndrome. Most patients with FAP have already been diagnosed with polyps when they reach early adulthood. The majority of polyps are located in the left colon, including the splenic flexure and descending, sigmoid, and rectosigmoid colons. Cancers typically develop between ages twenty and thirty but can occur at any age.
Symptoms: The patient with Gardner syndrome may experience a wide variety of symptoms, depending on the body systems affected. The most common are gastrointestinal symptoms and include rectal bleeding, pain, diarrhea or constipation, nausea, and vomiting. Multiple cysts may be found on the patient’s body, particularly on the face, scalp, and extremities. They usually cause no symptoms, but they may become itchy or inflamed.
Screening and diagnosis: When a person has a family history of Gardner syndrome, blood tests can be performed for deoxyribonucleic acid (DNA) analysis and to screen for APC gene mutations. A positive test result for an APC mutation is sufficient for diagnosis. Laboratory testing to determine the extent of the disease includes stools for occult blood, thyroid function studies, and liver function tests as well as basic chemistries, blood counts, and electrolyte levels. Imaging studies include upper and lower gastrointestinal series, esophagogastroduodenoscopy, colonoscopy, computed (CT) scanning, (MRI), and ultrasonography to screen for polyps and tumors, as well as skull, facial, and dental x-rays to evaluate oral abnormalities and screen for tumors. Most testing procedures should be performed on an annual basis after initial diagnosis.
Treatment and therapy: Extensive surgery is indicated when colon polyps are identified in a patient with Gardner syndrome because of the risk of colon cancer. Osteomas of the skull and dental abnormalities should be removed if they interfere with normal function or are deforming. Cysts on the skin may require removal if they are producing symptoms or are disfiguring. The necessity of surgery to remove other tumors is evaluated based on their location, type of tumor, patient’s surgical risk, and potential risks of not removing them.
Chemotherapy has been shown to reduce polyps following colon surgery. Treatment with sulindac, a nonsteroidal anti-inflammatory drug, is recommended for patients with intra-abdominal desmoids, which may be unresectable; oral calcium has been shown to reduce the colon cancer risk; and sulindac, tamoxifen, or a combination of both is recommended for other manifestations of the disease. Research into other treatments, including gene therapy, is ongoing.
Prognosis, prevention, and outcomes: The five-year relative survival rate for patients with metastasized (late-stage) colorectal cancer is 13 percent as compared with 91 percent for those with a localized colorectal tumor. Recurrence after treatment is possible; however, guidelines for follow-up care vary. There is no prevention for Gardner syndrome.
Bibliography
Armaghany, Tannaz, et al. “Genetic Alterations in Colorectal Cancer.” Gastrointestinal Cancer Research, vol. 5, no. 1, 2012, pp. 19–27.
Butler, Jonathan, et al. “Gardner Syndrome: Review and Report of a Case.” Oral Oncology Extra, vol. 5, no. 41, 2005, pp. 89–92.
Charifa, Ahmad, et al. “Gardner Syndrome.” National Library of Medicine, StatPearls, 12 Feb. 2024, www.ncbi.nlm.nih.gov/books/NBK482342/. Accessed 12 July 2024.
“Colorectal Cancer.” American Cancer Society, 2024, www.cancer.org/cancer/types/colon-rectal-cancer.html. Accessed 12 July 2024.
“Colorectal Cancer Risk Factors.” American Cancer Society, 29 Jan. 2024, www.cancer.org/cancer/types/colon-rectal-cancer/causes-risks-prevention/risk-factors.html. Accessed 12 July 2024.
“Familial Adenomatous Polyposis.” MedlinePlus, US Natl. Lib. of Medicine, 1 Oct. 2013, medlineplus.gov/genetics/condition/familial-adenomatous-polyposis/. Accessed 12 July 2024.
Hansmann, A., et al. “High-Dose Tamoxifen and Sulindac as First-Line Treatment for Desmoid Tumors.” Cancer, vol. 100, no. 3, 2004, pp. 612–20.
Hedge, Madhuri, et al. “ACMG Technical Standards and Guidelines for Genetic Testing for Inherited Colorectal Cancer (Lynch Syndrome, Familial Adenomatous Polyposis, and MYH-Associated Polyposis).” Genetics in Medicine, vol. 16, 2014, pp. 101–16.
Menon, Gopal, et al. “Familial Adenomatous Polyposis.” National Library of Medicine, StatPearls, 5 May 2024, www.ncbi.nlm.nih.gov/books/NBK538233/. Accessed 12 July 2024.
Panjwani, Sapna, et al. “Gardner’s Syndrome.” Journal of Clinical Imaging Science, vol. 1, 2011, p. 65.