Mosaicism and Neoplastic Outcomes in Epidermal Nevus Syndromes

Mosaic epidermal nevus syndromes arise from postzygotic mutations that generate lines or patches of affected skin and often involve extracutaneous organs. Activating variants in genes encoding proteins of the RAS-MAPK and PI3K-AKT pathways, notably HRAS, KRAS, FGFR3 and PIK3CA, lead to a spectrum of disorders characterised by epidermal nevi, developmental anomalies and a propensity for benign and malignant tumours. Clinical manifestations vary from isolated linear nevi to complex syndromes such as Schimmelpenning–Feuerstein–Mims syndrome, oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. The mosaic distribution of mutated cells can affect skin, nervous system, eyes and skeletal structures. While most secondary tumours are benign, there is a measurable risk of malignant transformation to basal cell carcinoma, rhabdomyosarcoma or other neoplasms. Advances in molecular diagnostics and non-invasive imaging have improved early detection, enabling targeted surveillance and potential use of MEK or PI3K inhibitors to mitigate oncogenic signalling. Understanding the interplay between somatic mosaicism and neoplastic progression is crucial for prognostication, genetic counselling and development of personalised therapies.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Mosaicism and Neoplastic Outcomes in Epidermal Nevus Syndromes publication trend

The graph below shows the total number of articles in mosaicism and neoplastic outcomes in epidermal nevus syndromes across all publications each year (not limited to Nature Index journals).

Technical terms

Mosaicism: Presence of genetically distinct cell populations within an individual originating from postzygotic mutations.

Postzygotic mutation: Genetic change occurring after fertilisation, leading to somatic mosaicism.

RASopathies: Disorders caused by aberrant signalling through the RAS-MAPK pathway, often involving skin, heart and nervous system abnormalities.

Epidermal nevus: Congenital hamartoma of the epidermis following Blaschko lines due to mosaic gene variants.

Nevus sebaceous: A type of epidermal nevus with sebaceous gland proliferation, prone to secondary tumours.

Blaschko lines: Embryonic skin cell migration patterns visible in mosaic skin disorders.

Reflectance confocal microscopy: A non-invasive imaging technique providing in vivo horizontal optical sections of the skin at near-histological resolution.

References

1. Nevus Sebaceous of Jadassohn in Adults—Can Reflectance Confocal Microscopy Detect Malignant Transformation?. Diagnostics (2023).
2. Identification of Codon 146 KRAS Variants in Isolated Epidermal Nevus and Multiple Lesions in Oculoectodermal Syndrome: Confirmation of the Phenotypic Continuum of Mosaic RASopathies. International Journal of Molecular Sciences (2022).
3. Case Report: Sequential postzygotic HRAS mutation and gains of the paternal chromosome 11 carrying the mutated allele in a patient with epidermal nevus and rhabdomyosarcoma: evidence of a multiple-hit mechanism involving HRAS in oncogenic transformation. Frontiers in Genetics (2023).