Dermatologic Manifestations of Gardner Syndrome 

Updated: Apr 05, 2021
Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD 



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 findings[2] of Gardner syndrome include epidermoid cysts, desmoid tumors, and other benign tumors. Polyps have a 100% risk of undergoing malignant transformation (see the figure below); consequently, early identification of Gardner syndrome is critical.[3, 4]

Adenoma-to-carcinoma sequence on a cellular level. Adenoma-to-carcinoma sequence on a cellular level.


Gardner syndrome is genetically linked to band 5q21, the adenomatous polyposis coli locus.[5] 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. Novel pathogenic alterations have been described.[6]  A novel large germline fragment deletion of the adenomatous polyposis coli (APC) gene was identified in a Chinese family with this syndrome.[7]


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



In the 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%).


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.


With adequate screening, long-term control of colorectal tumors is possible, with desmoid tumors determining the survival and quality of life for many patients.[8]  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). A genetic variant with an aggressive early childhood phenotype has been described.[9]

Patient Education

For patient education resources, see the Cancer and Tumors Center, as well as Colon Cancer.




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.[10] Previously undiagnosed Gardner syndrome may be detected when the patient is evaluated for multiple impacted and unerupted teeth. Dentists may play a pivotal role in detecting craniomaxillofacial osteomas, a major criterion for Gardner syndrome.[11]

Physical Examination

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 (may be visceral, including intracranial[12] )

  • 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%, whereas it is rare in the general population.[13]

  • Osteomas are required to make the diagnosis of Gardner syndrome. The mandible is the most common location. They may be widespread in the jaw.[14] 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 in this syndrome include multiple impacted or unerupted teeth, supernumerary teeth, hypodontia, compound odontomes, and dentigerous cyst.[15, 16] These dental findings may become evident several years before the intestinal ones.[17]

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)[18] ; craniopharyngioma are usually suprasellar, but have been described in an atypical location in Gardner syndrome[19]

  • Thyroid carcinoma (especially in female patients): This papillary thyroid carcinoma is a distinct type of follicular cell neoplasm histologically characterized by cribriform-morular features.[20] Its incidence may have been underestimated.

  • Osteosarcoma

  • Chondrosarcoma

  • Hepatoblastoma

  • Liposarcoma

  • Mucoepidermoid carcinoma[21]


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.

Desmoid tumors are a significant cause of the morbidity and mortality in those with Gardner syndrome; surgical procedures to excise them are complex.[13]



Diagnostic Considerations

Multiple osteomas of the jaws are a hallmark of Gardner syndrome (familial adenomatous polyposis [FAP]); nonsyndromic cases are typically solitary.[16, 22]

Epidermoid cysts of Gardner syndrome may exhibit pilomatricomalike changes.[23] Pilomatricomas themselves may be associated with genetic diseases, such as Curschmann-Steinert myotonic dystrophy and Rubinstein-Taybi syndrome.[24]

Differential Diagnoses



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.

Most parents believed it was their responsibility to inform young family members about genetic testing results, an often emotionally challenging matter encouraging preventive screening and possible lifestyle adaptions.[25]

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.[26]


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.[23] 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.

The Gardner fibroma, a soft tissue tumor of children and young adults, displays a bland hypocellular proliferation of haphazardly arranged coarse collagen fibers with a bland hypocellular proliferation of inconspicuous spindle cells, small blood vessels, and a sparse mast cell infiltrate. Immunohistochemically, many show nuclear reactivity for beta-catenin and most, if not all, have nuclear reactivity for both cyclin-D1 and C-myc. These fibromas may serve as an indicator for familial Gardner syndrome or similar disorder.[27, 28]



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 excision[29] or use of intralesional steroids if the cysts are inflamed. Conservative management with chemotherapy or tyrosine kinase inhibitors is now being favored.[30]

Antiestrogens and anthracycline-containing regimens may have a favorable radiological response rate against desmoid tumors and may be a viable option in some patients.[31]

Most parents believed it was their responsibility to inform young family members about genetic testing results, an often emotionally challenging matter encouraging preventive screening and possible lifestyle adaptions.[25]

Surgical Care

Colectomy[32] 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. Total gastroduodenectomy with pancreatic preservation may be desirable in some settings.[33]

Generally, cutaneous findings do not require treatment. Osteomas may require excision if they are severely deforming or if they interfere with function.

Also see the General Surgery article Gardner Syndrome.


Questions & Answers