Familial melanoma

Familial melanoma, also known as familial atypical multiple mole melanoma syndrome (FAMMM), hereditary melanoma, or dysplastic nevus syndrome, is a genetic predisposition to developing cutaneous malignant melanoma, a cancer arising from melanocytes (pigment-producing cells) in the skin. Individuals with familial melanoma typically develop melanoma at a younger age than sporadic cases and may develop multiple primary melanomas over their lifetime. The condition is characterized by the presence of numerous atypical (dysplastic) nevi and an increased lifetime risk of melanoma that can exceed 50-90% depending on the specific genetic variant and family history. The most commonly implicated gene is CDKN2A (located on chromosome 9p21), which encodes the tumor suppressor proteins p16INK4a and p14ARF, both critical regulators of cell cycle control. Mutations in CDK4 on chromosome 12q14 are a less common cause. Some families with CDKN2A mutations also carry an elevated risk of pancreatic cancer and, in certain populations, other cancers including those of the breast and central nervous system. Additional susceptibility genes such as BAP1, POT1, TERT, ACD, and TERF2IP have been identified in smaller subsets of families, often conferring moderate penetrance. Management of familial melanoma centers on early detection and prevention. Affected individuals and at-risk family members are advised to undergo regular full-body skin examinations by a dermatologist, typically every 3-6 months, along with dermoscopic monitoring and total body photography. Sun protection measures including avoidance of ultraviolet radiation are strongly recommended. Genetic counseling and testing for CDKN2A and other relevant genes can help identify at-risk relatives. When melanoma is detected, treatment follows standard oncologic protocols including surgical excision, sentinel lymph node biopsy, immunotherapy (such as checkpoint inhibitors), targeted therapy (BRAF/MEK inhibitors for tumors harboring BRAF mutations), and radiation therapy depending on stage. Screening for pancreatic cancer may also be recommended in families with CDKN2A mutations.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Familial melanoma