Dysplastic nevus syndrome

Overview

Dysplastic nevus syndrome, also known as familial atypical multiple mole melanoma (FAMMM) syndrome, is a hereditary condition characterized by the presence of numerous atypical (dysplastic) moles and a significantly increased risk of developing melanoma, a serious form of skin cancer. People with this syndrome may have dozens to hundreds of moles, many of which appear unusual in size, color, or shape. While not all dysplastic nevi become cancerous, they are considered markers of melanoma risk, particularly in individuals with a family history of the disease.

Causes

Dysplastic nevus syndrome is most often inherited in an autosomal dominant pattern, meaning a mutation in just one copy of the gene from either parent can cause the condition. The most commonly affected gene is CDKN2A, which encodes proteins involved in cell cycle regulation and tumor suppression. Mutations in this gene impair the body’s ability to control cell growth, increasing the risk of melanoma. Other genetic mutations, such as those in the CDK4 gene, may also be involved in some families.

Environmental factors, particularly ultraviolet (UV) radiation from the sun or tanning beds, play a significant role in triggering malignant transformation in predisposed individuals.

Symptoms

The main clinical feature of dysplastic nevus syndrome is the presence of multiple dysplastic moles, often along with a family history of melanoma. Key characteristics include:

• Numerous moles: Often more than 50–100, scattered across the body.

• Dysplastic nevi: Moles that are irregular in size, color, or border. They may be larger than 5 mm, have multiple colors (tan, brown, pink), and have an indistinct or ragged outline.

• Sun-exposed and non-sun-exposed areas: Moles can appear anywhere, including on the scalp, breasts, buttocks, or other less visible areas.

• Family history: One or more close relatives with melanoma, especially if diagnosed at a young age.

Diagnosis

Diagnosis is based on clinical evaluation, dermatologic examination, and family history. Diagnostic steps include:

• Full-body skin exam: Conducted by a dermatologist to evaluate the number and appearance of moles.

• Dermatoscopy: A tool used to examine pigmented lesions in greater detail to distinguish benign from suspicious features.

• Skin biopsy: Performed on atypical or changing moles to determine whether they are dysplastic or malignant.

• Genetic testing: Recommended for individuals with a strong family history of melanoma. Testing for mutations in genes like CDKN2A may confirm the diagnosis.

• Family history assessment: Evaluating patterns of melanoma or pancreatic cancer in relatives can support the diagnosis.

Treatment

There is no cure for dysplastic nevus syndrome, but management focuses on early detection and prevention of melanoma. Strategies include:

• Regular dermatological exams: Every 3 to 12 months, depending on individual risk.

• Total body photography and mole mapping: Helps monitor changes over time in existing moles and detect new ones.

• Excisional biopsy: Suspicious or changing moles may be surgically removed to rule out melanoma.

• Sun protection: Daily use of broad-spectrum sunscreen (SPF 30+), protective clothing, and avoidance of tanning beds and peak sunlight hours.

• Genetic counseling: For affected individuals and at-risk family members to understand the inheritance pattern and consider testing.

Some individuals may undergo elective removal of highly atypical moles or those located in areas difficult to monitor.

Prognosis

The prognosis for individuals with dysplastic nevus syndrome depends on vigilance and early detection. While not all dysplastic moles progress to melanoma, individuals with this syndrome have a significantly higher lifetime risk of developing melanoma—some estimates suggest up to a 70% risk, particularly if there is a strong family history. Regular monitoring, early removal of suspicious lesions, and strict sun protection can significantly reduce the risk of advanced melanoma and improve outcomes. With proper surveillance, many individuals with dysplastic nevus syndrome live normal, healthy lives.