eMedicine Specialties > Dermatology > Internal Medicine

Gardner Syndrome

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School

Updated: Jul 17, 2009

Introduction

Background

Gardner syndrome, a variant of familial adenomatous polyposis (FAP),¹ is an autosomal dominant disease characterized by GI polyps, multiple osteomas, and skin and soft tissue tumors. Cutaneous findings² of Gardner syndrome include epidermoid cysts, desmoid tumors, and other benign tumors. Polyps have a 100% risk of undergoing malignant transformation; consequently, early identification of Gardner syndrome is critical.³

Pathophysiology

Gardner syndrome is genetically linked to band 5q21, the adenomatous polyposis coli locus.⁴ FAP and Gardner syndrome are believed to be variants of the same condition. The wider spectrum of abnormalities found in Gardner syndrome may represent variable penetrance of a common genetic mutation.

Frequency

United States

One person per million population is diagnosed with Gardner syndrome. The incidence of FAP is 1 case per 8000 people. The most common cutaneous finding in patients with Gardner syndrome is epidermoid cysts (50-65%).

Mortality/Morbidity

Unless surgical transection is performed, GI polyps may progress to malignancy in almost 100% of Gardner syndrome patients (rates vary from 58-100% in studies).

Age

Although colonic polyps begin to form in puberty, the average age at Gardner syndrome diagnosis is 22 years. Osteoma formation precedes polyposis. Usually, progression to malignancy is observed in patients aged 30-50 years. The average age by which malignancy is diagnosed is 39.2 years.

Clinical

History

Many skin findings of Gardner syndrome are evident on full body examination; however, the patient's history of the age at onset and whether lesions are present in family members is important.
Cysts in Gardner syndrome patients are usually asymptomatic, but they may be pruritic and/or inflamed.
More than half the patients with Gardner syndrome have dental anomalies.⁵ Previously undiagnosed Gardner syndrome may be detected when the patient is evaluated for multiple impacted and unerupted teeth.

Physical

A full body skin examination for skin tumors and epidermal inclusion cysts is necessary in Gardner syndrome.

Several factors differentiate cutaneous cysts associated with Gardner syndrome from ordinary cysts.
- Epidermoid cysts of Gardner syndrome occur at an earlier age (around puberty) than ordinary cysts and in less common locations, such as the face, the scalp, and the extremities.
- Gardner syndrome cysts tend to be multiple and are present in the multiple form in 50-65% of patients.
- Similar to ordinary epidermal inclusion cysts, cysts in Gardner syndrome are usually asymptomatic; however, they may be pruritic and/or inflamed, and they may rupture.
Other skin signs in Gardner syndrome include the following:
- Fibromas
- Lipomas
- Leiomyomas
- Neurofibromas
- Pigmented skin lesions
Noncutaneous features of Gardner syndrome include the following:
- Desmoid tumors occur as swelling in the anterior abdominal wall and are often preceded by surgical trauma. The incidence of desmoid tumors in FAP is 8.9%.
- Osteomas are required to make the diagnosis of Gardner syndrome. The mandible is the most common location. They may be widespread in the jaw.⁶ However, osteomas may occur in the skull and the long bones. Osteomas precede clinical and radiologic evidence of colonic polyposis; therefore, they may be sensitive markers for the disease.
- Colonic adenomatous polyps have a 100% risk of transformation to colonic adenocarcinoma.
- Multifocal pigmented lesions of the fundus are seen in 80% of patients and may present shortly after birth. These lesions can be the first marker of disease.
- Dental abnormalities (eg, unerupted teeth, supernumerary teeth) may occur.
Other associated neoplasms in Gardner syndrome include the following:
- Periampullary carcinoma (ampulla of Vater; reported in 12% of patients with FAP, usually after colectomy)
- CNS tumors, such as medulloblastoma, glioblastoma, and craniopharyngioma (found in FAP subgroup in Turcot syndrome)
- Thyroid carcinoma (especially in female patients)
- Osteosarcoma
- Chondrosarcoma
- Hepatoblastoma
- Liposarcoma

Causes

The cause of Gardner syndrome is genetic, with autosomal dominant inheritance.

Differential Diagnoses

Eruptive Vellus Hair Cysts

Workup

Laboratory Studies

Thyroid screening by physical examination and ultrasonography is recommended in Gardner syndrome.
Chromosome studies from peripheral blood lymphocytes and allele-specific expression assay can be performed.
Screen all first-degree relatives of patients with Gardner syndrome or FAP.

Imaging Studies

Imaging studies are essential for screening patients and family members who are affected.
- Panoramic radiography of the mandible can demonstrate subtle opacities at an early age.
- Long bone radiographs may demonstrate osteomas or hyperostosis.
- Ultrasonography is performed to screen for thyroid tumors.
- Van Epps et al reported seeing epidermal inclusion cysts on a CT scan from a patient with Gardner syndrome.¹⁰
Also see the Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline.¹¹

Procedures

Perform an ophthalmologic examination at an early age to detect pigmented lesions of the fundus.
Fecal occult blood, sigmoidoscopy/colonoscopy, and upper GI endoscopy are required at least every 1-2 years until the patient reaches age 50 years.

Histologic Findings

Pathologic findings of the epidermoid cysts of Gardner syndrome are similar to findings in non–Gardner syndrome cysts; however, many have pilomatricomalike changes.⁸ In 1 study, 63% of cysts examined from 7 patients with Gardner syndrome demonstrated 1 or more matricoma features, such as columns of shadow cells, calcification, and basophilic matrixlike cells in the cyst lining.

Treatment

Medical Care

Treatment of the cutaneous manifestations of Gardner syndrome depends on the symptomatic or cosmetic nature and the location of the cysts. Treatment is similar to that used for ordinary cysts and involves excision¹² or use of intralesional steroids if the cysts are inflamed.

Surgical Care

Colectomy¹³ is recommended for Gardner syndrome patients if 30 or more polyps are detected on colonoscopy or if biopsy results reveal dysplasia or malignant degeneration.
Preserving the rectum results in a 25-59% chance of rectal carcinoma occurring in Gardner syndrome patients; therefore, rectal mucosal resection is recommended.
Generally, cutaneous findings do not require treatment.
Osteomas may require excision if they are severely deforming or if they interfere with function.
Also see eMedicine's General Surgery article Gardner Syndrome.

Follow-up

Complications

In Gardner syndrome, polyps have a 100% risk of undergoing malignant transformation; therefore, surgical transection is indicated.
Females are at higher risk for thyroid carcinoma than males. Other neoplasms possible with Gardner syndrome include periampullary carcinoma, CNS tumors, osteosarcoma, chondrosarcoma, hepatoblastoma, and liposarcoma.

Patient Education

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education article Colon Cancer.

Miscellaneous

Medicolegal Pitfalls

Failure to diagnose Gardner syndrome is a pitfall. Polyps have a 100% risk of undergoing malignant transformation; consequently, early identification of the disease is critical.

References

Gu GL, Wang SL, Wei XM, Bai L. Diagnosis and treatment of Gardner syndrome with gastric polyposis: a case report and review of the literature. World J Gastroenterol. Apr 7 2008;14(13):2121-3. [Medline].
Ascari-Raccagni A, Baldari U, Righini MG. Cutaneous symptoms of Gardner's syndrome. J Eur Acad Dermatol Venereol. Jan 1999;12(1):80-1. [Medline].
Hood AB, Krush AJ. Clinical and dermatologic aspects of the hereditary intestinal polyposes. Dis Colon Rectum. Aug 1983;26(8):546-8. [Medline].
Elkharwily A, Gottlieb K. The pancreas in familial adenomatous polyposis. JOP. Jan 8 2008;9(1):9-18. [Medline].
Madani M, Madani F. Gardner's syndrome presenting with dental complaints. Arch Iran Med. Oct 2007;10(4):535-9. [Medline].
Lee BD, Lee W, Oh SH, Min SK, Kim EC. A case report of Gardner syndrome with hereditary widespread osteomatous jaw lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Mar 2009;107(3):e68-72. [Medline].
Kaplan I, Nicolaou Z, Hatuel D, Calderon S. Solitary central osteoma of the jaws: a diagnostic dilemma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Sep 2008;106(3):e22-9. [Medline].
Pujol RM, Casanova JM, Egido R, Pujol J, de Moragas JM. Multiple familial pilomatricomas: a cutaneous marker for Gardner syndrome?. Pediatr Dermatol. Dec 1995;12(4):331-5. [Medline].
Wachter-Giner T, Bieber I, Warmuth-Metz M, Brocker EB, Hamm H. Multiple pilomatricomas and gliomatosis cerebri--a new association?. Pediatr Dermatol. Jan-Feb 2009;26(1):75-8. [Medline].
Van Epps KJ, Kuszyk BS, Hofmann LV, Fishman EK. Epidermoid inclusion cysts seen on CT of a patient with Gardner's syndrome. AJR Am J Roentgenol. Sep 1999;173(3):858-9. [Medline].
Desch CE, Benson AB 3rd, Somerfield MR, et al. Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. Nov 20 2005;23(33):8512-9. [Medline].
Marshall KA, Kuhlmann TP, Horowitz JH, Silloway KA, Edlich RF. Excision of multiple epidermal facial cysts in Gardner's syndrome. Am J Surg. Nov 1985;150(5):615-6. [Medline].
Perniciaro C. Gardner's syndrome. Dermatol Clin. Jan 1995;13(1):51-6. [Medline].
Cotran RS, Kumar V, Collins T. Pathologic Basis of Disease. Philadelphia, Pa: WB Saunders; 1999:831.
Luk GD. Diagnosis and therapy of hereditary polyposis syndromes. Gastroenterologist. Jun 1995;3(2):153-67. [Medline].
Narisawa Y, Kohda H. Cutaneous cysts of Gardner's syndrome are similar to follicular stem cells. J Cutan Pathol. Apr 1995;22(2):115-21. [Medline].

Keywords

Gardner syndrome, Gardner's syndrome, Gardners syndrome, familial adenomatous polyposis, FAP, gastrointestinal polyps, GI polyps

Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Sungnack Lee, MD, Vice President of Medical Affairs, Professor, Department of Dermatology, Ajou University School of Medicine, Korea
Sungnack Lee, MD is a member of the following medical societies: American Dermatological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Karen Allen, MD, and Raul Del Rosario, MD, and previous Chief Editor, William D. James, MD, to the development and writing of this article.

Further Reading