Gardner Syndrome

From EyeWiki
All authors and contributors:
Assigned editor:
Assigned status Update Pending
 by Nimesh Patel, MD on June 23, 2022.

Disease Entity

Gardner Syndrome ICD 10 code: D12.6


Gardner syndrome is a rare phenotypic variant of familial adenomatous polyposis (FAP). Both Gardner syndrome and FAP are characterized by the numerous adenomatous polyps lining the intestinal mucosal surface.[1] However, Gardner syndrome has characteristic polyps in the colon and osteomas that help distinguish the disease from FAP. [2] Gardner syndrome can also present with ocular manifestations that include the presence of multiple patches of congenital hypertrophy of the retinal pigment epithelium (CHRPE). The presence of multiple and bilateral CHRPE is considered a clinical disease marker and is useful for early detection in individuals that are at risk. However, the absence of CHRPE cannot be considered a negative predictive indicator of Gardner syndrome. [3]


In the United States, the prevalence of Gardner syndrome is 1 in 1,000,000 and has an incidence of 1 in 8,000. [1] While the penetrance of the gene is nearly 100% in those affected with Gardner syndrome, there is variation in the expression both between and within affected families. [4]


Gardner syndrome is an autosomal dominant disorder caused by germline mutations in the adenomatous polyposis coli (APC) gene. [5] APC gene is located on chromosome 5, within band 5q21, and encodes for a tumor suppressor gene. While Gardner syndrome is commonly recognized with mutations within the APC gene, there are other mutations that have been linked as possible causes of Gardner syndrome. Mutations of TP53 on chromosome 17, a deletion of the colon cancer gene (DCC) on chromosome 18, and loss of DNA methylation on chromosome 12 which causes a mutation of the RAS gene have all been linked as possible causes of Gardner syndrome. [6][7][8]

Risk Factors

The earliest and most common extra-colonic finding in Gardner syndrome is CHRPE and is found in nearly 90% of patients. [9] However, ocular findings in Gardner Syndrome are often incidental so family history is the most important assessment of a patient's risk. Since Gardner syndrome is an autosomal dominant disorder, offspring of an affected parent pose a 50% chance of inheriting the disorder. Less commonly, with no known causes, Gardner syndrome can result from de novo mutations in the APC gene. De novo mutations account for approximately 20% of individuals diagnosed with Gardner syndrome and have an absent family history of the disorder. [10]


APC gene is located on chromosome 5 and is genetically linked to band 5q21. The genetic material contained in the APC gene is used to transcribe the APC protein which is over 2800 amino acids in length. Disease severity and extracolonic findings are associated with the location of the APC mutation.[11] APC protein functions as a tumor suppressor gene and plays an important role in cell division, regulation and growth. APC protein is also important in mediating cell adhesion by helping regulate the manner of attachment of cells to other cells within the tissue. The protein beta catenin is tightly regulated by the APC gene. Beta catenin is responsible for regulating proteins that are responsible for stimulating cell division. Mutations in the APC gene cause inactivation of the beta catenin protein resulting in the overactivation of proteins responsible for cell division.[1] Loss of function in the APC protein is thought to be the earliest event in the formation of adenomas. [2]


Diagnosis of Gardner syndrome is established through molecular genetic testing. [12]


Patients may be asymptomatic or may report cramping, diarrhea, rectal bleeding, constipation, and/or vomiting. [1]

Physical Exam

Ophthalmic Abnormalities

  • Detection of CHRPE is often the earliest clinical indicator for Gardner syndrome. Compared to retinal pigmented epithelial cells (RPE), CHRPE cells are columnar to cuboidal and are taller than the unaffected RPE. [1] Despite CHRPE being an early clinical indicator, not all patients that present with CHRPE should be considered for suspicion of Gardner syndrome. The characteristics of CHRPE related to Gardner syndrome are different from benign variants of CHRPE. [13]

Characteristics of Gardner Syndrome related CHRPE

  1. Bilateral
  2. Occurrence in multiple quadrants
  3. Pisiform shape
  4. Irregular Borders

Systemic Abnormalities

Patients with Gardner syndrome classically present with multiple gastrointestinal polyps, osteomas of the mandible and skull, epidermal cysts, fibromatosis, and development of extra teeth. [1] Dermatological findings may also exist such as skin tumors or epidermal inclusion cysts. [2]

Differential Diagnosis

The four main phenotypes associated with mutations in the APC gene are Familial Adenomatous Polyposis (FAP), Gardner Syndrome, Turcot syndrome, and attenuated forms of familial polyposis. However, unlike the other phenotypes associated with APC gene mutations, Gardner syndrome has characteristic polyps in the colon, osteomas and abnormalities in the retinal epithelium. [1]

  • Familial Adenomatous Polyposis
  • Turcot Syndrome
  • Attenuated forms of familial polyposis


General Treatment

Eye Abnormalities

Active intervention is not generally indicated or required. In rare cases, proton beam therapy has been indicated. [14]

Systemic Abnormalities

Once individuals become aware of familial inheritance or are diagnosed with Gardner syndrome, treatment is aimed at prevention of polyp growth in the colon. Treatment often includes the use of sulindac or celecoxib. Sulindac is an NSAID and celecoxib is a COX2 inhibitor which both aid in decreasing polyps growth. If the disease progresses and more than 20 polyps are present then removal of the colon is recommended. [15]

Complications and Prognosis

Currently, there is no cure for Gardner syndrome. If surgery is not performed or polyp growth is not controlled, patients will inevitably develop colon cancer by the age of 40. As of now, management and surveillance of symptoms are first line treatment. Surveillance includes annual physical exams to monitor thyroid function, palpate liver, assess liver function, and abdominal ultrasound. Beginning at ages 20-25 abdominal CT should be assessed every 3 years along with monitoring the adrenal glands, small bowels and pancreas. [16]

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Charifa A, Jamil RT, Zhang X. Gardner Syndrome. [Updated 2021 Jun 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
  2. 2.0 2.1 2.2 Juhn E, Khachemoune A. Gardner syndrome: skin manifestations, differential diagnosis and management. Am J Clin Dermatol. 2010;11(2):117-22. doi: 10.2165/11311180-000000000-00000. PMID: 20141232.
  3. Laghmari M, Lezrek O. Congenital hypertrophy of the retinal pigment epithelium in Gardner’s syndrome. The Pan African medical journal. 2014;19:164. doi:10.11604/pamj.2014.19.164.4518
  4. Lewis RA( 1 ), Crowder WE( 2 ), Nussbaum RL( 2 ), Eierman LA( 3 ), Ferrell RE( 4 ). The Gardner Syndrome: Significance of Ocular Features. Ophthalmology. 91(8):916-925. doi:10.1016/S0161-6420(84)34213-0
  5. Giardiello FM, Brensinger JD, Peterson GM. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 2001; 121: 198-213
  6. Pinto RS, Simons A, Verma R, Bateman N. Gardener-associated fibroma: an unusual cause of upper airway obstruction. BMJ Case Rep. 2018 Sep 28;2018
  7. Yang A, Sisson R, Gupta A, Tiao G, Geller JI. Germline APC mutations in hepatoblastoma. Pediatr Blood Cancer. 2018 Apr;65(4)
  8. Kiessling P, Dowling E, Huang Y, Ho ML, Balakrishnan K, Weigel BJ, Highsmith WE, Niu Z, Schimmenti LA. Identification of aggressive Gardner syndrome phenotype associated with a de novo APC variant, c.4666dup. Cold Spring Harb Mol Case Stud. 2019 Apr;5(2)
  9. Wallis YL, Macdonald F, Hulten M, et al: Genotype-phenotype correlation between position of constitutional APC gene mutation and CHRPE expressed in FAP. Hum Gene. 1994;94:543-548.
  10. Jasperson KW, Patel SG, Ahnen DJ. APC-Associated Polyposis Conditions. 1998 Dec 18 [Updated 2017 Feb 2]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from:
  11. Nieuwenhuis MH, Vasen HF. Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Crit Rev Oncol Hematol. 2007;61:153-161
  12. Jasperson KW, Patel SG, Ahnen DJ. APC-Associated Polyposis Conditions. 1998 Dec 18 [Updated 2017 Feb 2]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from:
  13. Brent Deibert, Letisha Ferris, Noel Sanchez, Paul Weishaar. The link between colon cancer and congenital hypertrophy of the retinal pigment epithelium (CHRPE). American Journal of Ophthalmology Case Reports. 2019;15. doi:10.1016/j.ajoc.2019.100524
  14. Moulin AP, Zografos L, Schalenbourg A. RPE adenocarcinoma arising from a congenital hypertrophy of the RPE (CHRPE) treated with proton therapy. Klin Monatsbl Augenheilkd. 2014;231:411-41
  15. Carr S, Kasi A.  StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Nov 24, 2020. Familial Adenomatous Polyposis
  16. Healy JC, Reznek RH, Clark SK, et al. MR appearances of desmoid tumors in familial adenomatous polyposis. AJR Am J Roentgenol 1997; 465
The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website.