Gardner Syndrome

Are You Confident of the Diagnosis?

What you should be alert for in the history

Patients may have a family history of central nervous system (CNS) malignancy, or may have neurological symptoms present.

A review of systems might include a history of abnormal thyroid or liver function; or abnormalities in the adrenal glands, small bowels, or pancreas, found through an abdominal computed tomography (CT) with oral contrast. In addition, the patient may present with palpable rectal polyps or masses, desmoid tumors or osteomas, or thyroid masses. There may be bleeding from the rectum, diarrhea, fatigue, or epigastric pain.

Characteristic findings on physical examination

Patients may present with cutaneous and noncutaneous signs and symptoms.

Cutaneous findings may include osteomas of the mandible and skull, epidermal cysts, lipomas, fibromatoses, or skin tumors; or, epidermal inclusion cysts or epidermoid cysts that are not pilar or steatocystoma in origin (Figure 1, Figure 2, Figure 3).

Noncutaneous findings may include multiple bilateral pigmented ocular fundus lesions, also known as congenital hypertrophy of the retinal epithelium. Desmoid tumors (desmoid fibromatosis) are common. They occur in the abdomen, chest, and upper and lower extremities. Often affecting the tendons and ligaments, they can occur both inside and outside the viscera as well.

Finally, intestinal polyposis and colorectal adenocarcinoma are characteristic findings. These lesions are connected with several other neoplasms, including duodenal carcinomas around the ampulla of Vater, heptatoblastoma, papillary or follicular thyroid cancer, and adrenal adenomas.

Expected results of diagnostic studies

The diagnosis for Gardner syndrome is based on clinical suspicion, but the presence of osteomas, seen through x-ray imaging, is necessary to make the diagnosis. Genetic testing can be performed as well, looking at the germline mutation of adenomatous polyposis coli (APC) gene, which is genetically linked to chromosomal band 5q21.

Diagnosis confirmation

There are four main conditions that should be considered in the differential diagnosis of Gardner syndrome.

Familial adenomatous polyposis (FAP) is quite closely related. It has an initial sign of congenital hypertrophy of the retinal pigment epithelium. FAP’s key characterization of pathology is early development of hundreds to thousands of tubular adenomas in the large intestine, and associated features, including upper gastrointestinal polyps, extracolonic malignancies, and desmoid tumors

Turcot syndrome is characterized by multiple colorectal adenomatous polyps, along with tumors in the brain (glioblastoma multiforme, medulloblastoma). In Turcot’s, there are usually fewer than 100 intestinal polyps, and in addition, cafe-au-lait spots and basal cell carcinomas can be seen on the skin.

Attenuated FAP is characterized by fewer than 100 adenomatous polyps in the colon. Patients may present with extracolonic features such as gastric polyps or mandibular osteomas. In attenuated FAP, the diagnosis is usually later in life (mean age of 44 years), The right side of the colon tends to be more involved, and the rectum is usually spared.

Hereditary nonpolyposis colorectal cancer (HNPCC) syndrome must be considered. HNPCC, also commonly referred to as Lynch syndrome, is the most common form of hereditary colorectal cancer. HNPCC patients are at high risk for colorectal and endometrial carcinomas, and carcinomas of the stomach, pancreas, small bowel, ovary, hepatobiliary tract, brain, and upper uroepithelial tract

Who is at Risk for Developing this Disease?

Gardner syndrome is an autosomal dominantly inherited disease that is diagnosed in approximately one person per million (at an average age of 22 years). Unless surgical transection is performed, gastrointestinal polyps progress to malignancy in almost 100% of cases.

Importantly, osteoma formation precedes polyposis. Usually, progression to malignancy is observed in patients aged 30-50 years.

What is the Cause of the Disease?

Gardner syndrome, like FAP, is attributed to the mutation and corresponding loss of function of the APC gene. The gene is a multifunction tumor suppressor gene that mediates cell adhesion, signal transduction, and transcriptional activation. This is thought to be the earliest event in the formation of adenomas.


The loss-of-function mutation in the APC gene allows normal colonic epithelium to proliferate, which thickens the mucosa. In addition, beta-catenin binds to cell-cell adhesion molecules (cadherins) and is involved in the formation of adherens junctions of the epithelia.

Beta-catenin also binds to the APC domain and the interaction between the two attaches the APC domain to cellular adhesion and cellular development molecules. These APC mutations are generally sufficient for colorectal tumors to grow to about one centimeter in diameter, though some tumors may have developed along a pathway not involving APC.

Systemic Implications and Complications

A common complication is gastrointestinal polyp degeneration, characterized by gastrointestinal polyps and malignant degeneration. These can be managed by early detection and surgical excision.

Other associated conditions that have been documented to have an increased risk for malignancy include biliary-tree tumors, pancreatic cancer, thyroid cancer, hepatoblastoma, and (though rare) brain tumors, including medulloblastoma and astrocytoma.

Treatment Options

Treatment options are summarized in Table I.

Table I.
Medical Surgical Physical

Epidermoid cysts:

Injection of triamcinolone

Colorectal carcinoma:

Restorative proctocolectomy with ileal pouch-anal anastomosis with mucosectomy

Total colectomy with ileorectal anastomosis

Proctocolectomy with ileostomy


Systemic, following total colectomy



Oral calcium

Skin manifestations, including epidermoid cysts and fibromatoses:


Curettage and cautery

Mohs excision

Photodynamic therapy



Systemic, following drainage of cysts:

Antistaphylococcal antibacterials

Bacterial culture—to guide antibiotic therapy


Optimal Therapeutic Approach for this Disease

Once diagnosed, individuals should be referred to a gastroentrologist and opthalmologist for evaluation. Other consultants, such as neurologists, oncologists, endocrinologists, opthalmologists, and dentists should also be consulted when appropriate.

Evaluation by a geneticist is recommended. Geneticists can perform gene testing and screen family members.

An annual physical examination by the patient’s primary care provider is required. Thyroid examination should be done at these visits.

Surgery is the main effective method of management, and early intervention is crucial. The aim of surgery is to eliminate the risk of colorectal cancer, while preserving nearby anatomic functions. The surgical procedure of choice is the restorative proctocolectomy with ileal pouch-anal anastomosis with mucosectomy. This attempts to rid all colorectal mucosa, while denying the need for an ostomy.

An ileostomy is used only in cases of recurrent malignancies after an ileorectostomy. For total colectomy, sulindac, tamoxifen, or a combination of the two is recommended for desmoid polyps of the abdominal wall or for extra-abdominal manifestations.

For cutaneous therapy, skin manifestations are treated according to their specific type. Uninfected epidermoid cysts may respond to an injection of triamcinolone, whereas infected cysts may require incision and drainage, along with antistaphylococcal antibacterials, and bacterial culture.

Cafe-au-lait spots do not require medical care, but if spots are in conjunction with other diseases such as neurofibromatosis, monitoring of the associated condition is required.

Finally, treatment of basal cell carcinoma depends on the size, location, number, and type of lesions. Treatment may include excision, curettage and cautery, Mohs excision, photodynamic therapy, and cryotherapy.

Patient Management

Patient management includes short-term follow-up (days to weeks) to monitor for complications and response to surgical therapy. Routine skin examinations should be performed every 6-12 months.

Abdominal ultrasound, CT, or magnetic resonance imaging (MRI) may show intra-abdominal or abdominal wall desmoid tumors, or hepatoblastoma. A colonoscopy and esophagogastroduodenoscopy (EGD) is used for surveillance in most patients.

APC gene testing should be performed if a first-degree relative has Gardner syndrome. For patients with Gardner syndrome, it is suggested that the patient receive an annual colonoscopy.

Unusual Clinical Scenarios to Consider in Patient Management

When diagnosing Gardner syndrome, one may find a variety of dental complications. These may include impacted or unerupted teeth, congenitally missing teeth, hypercementosis, supernumerary teeth, dentigerous cyst, fused roots of the first and second molars, long and tapered roots of posterior teeth, and multiple caries.

What is the Evidence?

Juhn, E, Khachemoune, A. “Gardner syndrome: skin manifestations, differential diagnosis, and management”. Am J Clin Dermatol. vol. 11. 2010. pp. 117-22. (A comprehensive review on the clinical features, pathogenesis, differential diagnosis, and management of Gardner syndrome)

Tsao, H. “Update on familial cancer syndromes and the skin”. J Am Acad Dermatol. vol. Jun;42. 2000. pp. 939-69. (A review that focuses on the clinical and molecular aspects of familial cancer syndromes that affect the skin, with an excellent commentary on Gardner syndrome)

Giardiello, FM, Brensinger, JD, Peterson, GM. “AGA technical review on hereditary colorectal cancer and genetic testing”. Gastroenterology. vol. 121. 2001. pp. 198-213. (A clinical reference that details the pathogenesis of Gardner syndrome, and how genetic testing can help diagnosis it)

Itoh, H, Hirata, K, Ohsata, K. “Turcot’s syndrome and familial adenomatous polyposis associated with brain tumor: a review of related literature”. Int J Colorectal Dis. vol. 8. 1993. pp. 87-94. (A review of Turcot’s syndrome that aids in the differential diagnosis of Gardner syndrome)

Nandakumar, G, Morgan, JA, Silverberg, D. “Familial polyposis coli: clinical manifestations, evaluation, management and treatment”. Mount Sinai J Med. vol. Nov;71. 2004. pp. 384-91. (A review that discusses management and treatment, in regards to surgery, for Gardner syndrome)

Galiatsatos, P, Foulkes, WD. “Familial adenomatous polyposis”. Am J Gastroenterol. vol. Feb;101. 2006. pp. 385-98. ( A review of familial adenomatous polyposis that aids in the differential diagnosis of Gardner Syndrome)

Hulsken, J, Birchmeier, W, Behrens, J. “E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton”. J Cell Biol. vol. Dec;127. 1993. pp. 2061-9. (An article that was used to understand the pathophysiology and etiology of Gardner syndrome)

Knudsen, AL, Bisgaard, ML, Bulow, S. “Attenuated familial adenomatous polyposis (AFAP): a review of the literature”. Fam Cancer. vol. 2. 2003. pp. 43-55. (A review of attenuated familial adenomatous polyposis that aids in the differential diagnosis of Gardner syndrome)

Singhal, H. “Gardner syndrome”. (A short review article that has facts and other pertinent information about Gardner syndrome. In this context, it was used for its information on the etiology the disease.)

Schafer, WG, Hines, MK, Levy, BM. “A textbook on oral pathology”. 1974. pp. 43-4. (This book was included because it detailed the unusual oral complications that are sometimes seen with Gardner syndrome)