Gardner Syndrome

Babak Bina, D.M.D.; Boris Zats, D.D.S.; Myrodati Lyristis, D.M.D.; Arin Abrahamian, D.D.S.

After studying a family whose members had nine deaths from colon cancer within three generations (average age 34 years old), Dr. Eldon J. Gardner introduced “Gardner syndrome.”[2] Gardner syndrome is associated with intestinal polyposis, multiple osteomas, and skin and soft tissue tumors.[3,4,5] First reported by Fader, dental abnormalities include supernumerary teeth, unerupted teeth, fused molar roots and long, tapered roots of posterior teeth, and osteomas of both the maxilla and mandible.[6] Osteomas most often occur in the angle of the mandible, but they may occur in the skull, long bones and paranasal sinus cavities.[7] Multiple osteomas are the main skeletal indication of Gardner syndrome. They can be mistaken for tori, exostosis, odontomas, osteoid osteoma and cemento-ossifying fibroma.

Other manifestations of Gardner syndrome include abnormality of the retina of the eye; desmoid tumors; skin manifestations, such as epidermoid and sebaceous cysts; fibromas; neurofibroma; lipomas; leiomyomas; pigmented skin; papillary thyroid cancer osteosarcoma; chondrosarcoma; and hepatoblastoma.[4,8,9,10]

As per the NYU School of Medicine IRB, a case report is the external reporting (e.g., publication or poster/verbal presentation) of an interesting clinical situation or medical condition of a single patient. Case reports normally contain detailed information about an individual patient and may include demographic information and information on diagnosis, treatment, response to treatment, follow-up after treatment, as well as a discussion of existing relevant literature. The patient information used in this paper was originally collected solely for non-research purposes as the result of a clinical experience. Kindly see the completed self-certification form uploaded as a separate file indicating that this case report was not deemed to be human subject research, as per the NYU School of Medicine IRB. Hence, no informed consent was required. All procedures conducted were in accordance with the Declaration of Helsinki.

Today Gardner syndrome is considered to be a variant form of familial adenomatous polyposis (FAP). Gardner syndrome is caused by a mutation of a tumor suppressor gene “APC” (adenomatous polyposis coli), which is located on chromosome5 in the region 5q21-q22.[3,10,11] The location of the mutation on the APC gene can influence the nature of the entire colonic manifestation. Most of the cases of FAP demonstrate a strong family history, but up to 30% of cases can occur without any family history of the disorder. In about a third of patients, recessive mutations in the MYH gene have been found.[11] This gene is involved in DNA repair. Although diagnosis of FAP is based on clinical findings, genetic testing is indicated both for confirmation of diagnosis and for management of at-risk family members.

The onset of polyps is early puberty; and adenocarcinoma usually occurs by the third and fourth decades of life. By age 35, close to 95% of patients will have polyps.[12] Cancers may arise anywhere from late childhood to the 60s. Patients with polyps outnumbering more than 1,000 have a two- to three-times greater risk of malignant transformation than those with fewer than 1,000.[13] Confirmation strand gel electrophoresis and protein testing will identify 80% to 90% of sequence alterations in genes.[3] The results may take up to six weeks.

Treatment with NSAIDs and COX-2 inhibitors (celeoxib, rofecoxib) have been shown to decrease the number of polyps and their size in FAP, but whether this means lower chances of malignancy has yet to be established.[14,15] Elective colectomy, including rectal mucosal resection is recommended if 30 or more polyps exist or if positive for dysplasia. The types of resection are 1) proctocolectomy with ileostomy; 2) total colectomy with ileorectal anastomosis; and 3) proctocolectomy with ileal pouch anal anastomosis.[3] Regardless of complication, surgical resection is still the treatment of choice due to improved survival rate. Cutaneous lesions might require excision for cosmetic corrections. Osteomas might need to be excised if they interfere with function. Routine gastrointestinal tract screening is recommended in any individual with a diagnosis of FAP, as well as yearly ultrasonographic examination to rule out thyroid cancer.[3]

In 2007, a 28-year-old Hispanic female was referred to oral surgery for evaluation of multiple “bumps” in the lower jaw. Past medical history did not reveal any significant findings. The patient was not taking any medications and had no known drug allergies. She also denied having any past significant illnesses.

Extraoral examination revealed multiple pigmented skin lesions on her face, trunk and upper extremities. Intraoral examination revealed multiple missing permanent teeth and retained primary teeth, as well as multiple, hard to palpation, non-tender bony exostoses on both sides of the mandible.

The patient’s initial panoramic X-ray (Figure 1) showed multiple impacted permanent and supernumerary teeth and multiple opacities in the areas corresponding to bony exostoses. The CT scan of head and neck with contrast revealed heterogeneous sclerotic bony thickening involving the maxilla, mandible and ethmoid sinus areas (Figures 2,3).

The clinical and radiographic findings were consistent with that of Gardner syndrome; furthermore, the patient’s family history revealed that her mother and older sister died of colon cancer at the ages of 34 and 29, respectively. The patient also lost an aunt and two cousins to ovarian cancer.

Genetic counseling confirmed our clinical diagnosis. The patient was referred to a gastroenterologist, and a CT scan of the abdomen withcontrast was obtained, taking multiple contiguous 5 mm CT axial imagesthrough the abdomen and pelvis (Figure 4). All images were obtained during the renal excretory phase. The liver, spleen, pancreas and left adrenal gland were unremarkable. The scan revealed a 2.3 cm x 1.6 cmright adrenal gland mass that measured fatty in attenuation during the scan without contrast, suggesting adrenal gland adenoma. The kidneys excreted symmetrically, urinary bladder was mildly distended, and there was no intraluminal filling defects. The bowel was partially opacified, bowel loops not dilated, and there was a moderate amount of retained stool in the colon. The uterus appeared bulky, with a 1.4 cm x 1.1 cm right adnexal follicle. Multiple, round scleroticlesions were found within the pelvic bones. During the colonoscopy, thegastroenterologist discovered a few polyps that were removed in 2009 (Figures 5, 6). The patient was also referred to an ophthalmologist for further workups, which revealed no significant findings.

The patient was placed on celecoxib to help reduce recurrence and size of polyps and was referred for counseling to help cope with the stresses of her medical condition. The therapist also placed her on antidepressants. Over the course of the next 10 years, the patient had a series of procedures to either manage the symptoms or as preventative measures to slow down the progression of the disease. Multiple surgeries were performed for polypectomy and osteoma removal from the jaw in 2009 and 2010. In 2011, the patient had multiple surgeries for removal of desmoid tumors found in the right lower quadrant of the abdominal wall, ileostomy sites, spine, sacrum and pelvic bone. Between 2013 and 2014, ovarian cysts and superficial masses were found in both breasts and were removed. The patient also had a small bowel resection that same year due to discovery of a benign neoplasm, small intestine surgery, colectomy and hysterectomy. In 2016, the patient was diagnosed with adrenal adenoma and had multiple rounds of chemo and radiation to shrink the size of the intestinal tumors; additional desmoid tumors were found and removed.

During the course of all of these procedures, the patient developed anemia, Bell’s palsy, and hypopigmented spots on her legs and body. She also discovered that her brother was diagnosed with Gardner syndrome, but because he refused treatments, he has since developed colon cancer. Our patient, however, continues to remain cancer-free as of today. Currently, she is having sigmoidoscopy routinely every two months.

Early detection is of great importance in Gardner syndrome, and this case will further signify the role of dentists in detecting systemic diseases. In patients with Gardner syndrome, GI polyps, if untreated, will always transform to carcinomas between age 30 and 40.[4] Although the patient described here had classical clinical and familial signs of Gardner syndrome, her condition was not detected for 28 years. Due to early detection and surgical intervention, she remains cancer-free.

All of the authors certify that they will take public responsibility for the content, have contributed substantially to the drafting, and have approved the final version. None of the authors has any conflicts of interest with the contents. All of the authors attest that all applicable subject protection guidelines and regulations were followed in the conduct of this research. The work has not been published and is not under consideration elsewhere and does not duplicate or overlap other published work. Queries about this article can be sent to Dr. Bina at Babak.Bina@NYULangone.org.

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Babak Bina, D.M.D., FACD, FICD, FPFA, is director of the GPR Program at NYU Langone Health, Brooklyn, NY.

Boris Zats, D.D.S., is director, Oral & Maxillofacial Surgery, NYU Langone Health, Brooklyn, NY.

Myrodati Lyristis, D.M.D., is former chief resident, GPR Program, NYU Langone Health, Brooklyn, NY.

Arin Abrahamian, D.D.S., is former chief resident, GPR Program, NYU Langone Health, Brooklyn, NY.