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Brown. Rare Dis Orphan Drugs J. 2025;4:21 Rare Disease and
DOI: 10.20517/rdodj.2025.14
Orphan Drugs Journal

Review Open Access

The clinical landscape of cutaneous neurofibromas
in neurofibromatosis type 1

Rebecca M. Brown

Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Correspondence to: Dr. Rebecca M. Brown, Department of Neurology, The University of Alabama at Birmingham, 1020 Faculty
Office Tower, 510 20th Street South, Birmingham, AL 35233, USA. E-mail: rbrown23@uab.edu

How to cite this article: Brown RM. The clinical landscape of cutaneous neurofibromas in neurofibromatosis type 1. Rare Dis
Orphan Drugs J. 2025;4:21. https://dx.doi.org/10.20517/rdodj.2025.14
Received: 3 Mar 2025 First Decision: 21 Apr 2025 Revised: 5 Jun 2025 Accepted: 30 Jun 2025 Published: 23 Jul 2025

Academic Editor: Daniel Scherman Copy Editor: Ping Zhang Production Editor: Ping Zhang

Abstract
Neurofibromatosis type 1 (NF1) is a hereditary tumor predisposition syndrome that predisposes patients to tumors
derived from the neural crest cell population. One of the most prominent and well-recognized features is the
proclivity for nerve sheath tumors of the skin known as cutaneous neurofibromas (CNs). These tumors are benign
and have self-limited growth, but they exert a strong negative impact on patients’ quality of life. The only effective
treatments currently are procedural, and there are no available medications. This review addresses the cellular and
molecular characteristics of cutaneous neurofibromas with a focus on identifying novel therapeutic targets that
could complement existing approaches. Preclinical models, tumor evolution throughout the lifespan, genetic
associations with tumor phenotype, and a brief history of interventional clinical trials are also discussed.

Keywords: Cutaneous neurofibroma, skin tumor, neurofibromatosis, NF1, peripheral nerve sheath tumor,
rasopathy, neurocristopathy

INTRODUCTION
Neurofibromatosis Type 1 (NF1) is a relatively common autosomal dominant tumor-predilection syndrome
and neurocristopathy affecting approximately 1 in 3,000 individuals regardless of sex or ethnicity. Its
pathoetiology is dependent on the monoallelic loss of function of NF1, resulting in haploinsufficiency in
every tissue of the body. Subsequent somatic loss of the remaining allele results in disease manifestations

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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