The management of hereditary melanoma, FAMMM syndrome and germline CDKN2A mutations: a narrative review

Abstract

Familial atypical multiple mole melanoma (FAMMM) syndrome is a rare autosomal dominant disorder, in which patients present with a large number of melanocytic naevi and a strong history of malignant melanoma, usually at a young age. The most common genetic alteration, implicated in 40 per cent of FAMMM syndrome families, is a mutation of cyclin-dependent kinase inhibitor 2A (CDKN2A).1 CDKN2A encodes the tumour suppressor gene p16INK4a, a critical cell cycle inhibitor.2 The diagnosis and management of patients with FAMMM syndrome is relevant to the plastic surgeon who manages melanoma. However, clear guidelines on its diagnostic criteria and its relationship to associated but distinct syndromes, such as hereditary melanoma and B-K mole syndrome, are lacking in the extant literature. The aim of this review is to clarify the diagnostic criteria and management principles for FAMMM syndrome. We propose a new system of classifying FAMMM syndrome patients as a subset of all patients with hereditary melanoma. We also present a management algorithm for these distinct patient groups (FAMMM syndrome, hereditary melanoma and germline CDKN2A mutations).