The first constant sign of the syndrome, appearing between the ages of 4 and 10 (rarely later), are epidermoid cysts on the skin of the face, scalp, limbs, and occasionally the chest. These cysts often develop long before colorectal polyps, making early detection of the precancerous condition easier. Later, they may spread to the trunk, perineum, and limbs. The cysts may be present from birth or appear in early childhood and increase in number by the age of 20.

Other common skin tumors include trichoepitheliomas, keratoacanthomas, and lipomas. Fibrous neoplasms are common, especially at sites of trauma or surgery. Fibrosarcomas and leiomyomas of the stomach and intestines are occasionally seen.

Approximately 50% of affected individuals have bone changes, mainly in the jaw and skull (osteomas, hyperostoses), which develop in the first decade of life and have a benign course. The size of these growths is small and they are often multiple.

The most significant prognostic aspect of the syndrome is the diffuse precancerous adenomatous polyposis of the colon, which typically manifests in the second decade of life and is characterized by periodic bleeding, causing anemia and constipation. By age 35-40, more than 40% of affected individuals progress from adenomatous polyps to adenocarcinomas, significantly increasing the risk of developing cutaneous melanoma and tumors in other organs such as the thyroid, ovaries, adrenal glands, and liver.

Diagnosis is made on the basis of the characteristic clinical presentation, histologic findings and the detection of gastrointestinal polyps on systematic instrumental examination.

Diagnostically significant findings include pigmentary changes in the eye (hyperplasia of the retinal pigment epithelium).

Patients with multiple fibrous skin tumors or pilomatricomas should undergo further evaluation to exclude Gardner syndrome.

• Cowden disease
• Peutz-Jeghers syndrome
• Cronkhite-Canada syndrome
• Muir-Torre syndrome