Continuing medical education
Neurofibromatosis type 1

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Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder affecting approximately 1 in 3500 people. Significant advances in the understanding of the pathophysiology of NF1 have been made in the last decade. While no medical therapies for NF1 are currently available, trials are ongoing to discover and test medical treatments for the various manifestations of NF1, primarily plexiform neurofibromas, learning disabilities, and optic pathway gliomas. In addition, mutational analysis has become available on a clinical basis and is useful for diagnostic confirmation in individuals who do not fulfill diagnostic criteria or when a prenatal diagnosis is desired. There are several disorders that may share overlapping features with NF1; in 2007, a disorder with cutaneous findings similar to NF1 was described. This paper addresses the dermatologist's role in diagnosis and management of NF1 and describes the variety of cutaneous and extracutaneous findings in NF1 to which the dermatologist may be exposed.

Learning objectives

After completing this learning activity, participants should be able to discuss the indications and limitations of genetic testing in neurofibromatosis type 1, distinguish common and uncommon cutaneous findings, and recognize the dermatologist's role in diagnosis and management.

Section snippets

Genetics of neurofibromatosis type 1

Key points

  1. NF1 is an autosomal dominant disorder, with a nearly even split between spontaneous and inherited mutations.

  2. Segmental NF1 represents mosaicism.

Pathogenesis of neurofibromatosis type 1

Key point

  1. The NF1 gene codes for neurofibromin, a tumor suppressor protein.

Neurofibromin, the NF1 gene protein product, is a tumor suppressor expressed in many cells, primarily in neurons, glial, Schwann cells, and early in melanocyte development.20 This protein is a regulator of Ras guanosine triphosphatase activity (GTPase-activating protein) and as such serves as a regulator of the signals for cell proliferation and differentiation5 (Fig 1). The loss of function of neurofibromin may therefore remove

Diagnosis

Key points

  1. Some diagnostic criteria may not manifest until later in life.

  2. Clinical diagnostic criteria are not as sensitive in very young children.

Cutaneous manifestations

Key point

  1. Patients with NF1 may develop a variety of skin findings.

Dermatologists should quickly recognize not only the salient skin features but also the less common cutaneous findings, because these latter aspects may be the source of a referral. The common and uncommon cutaneous features are provided in Table II. The following is a brief explanation of these findings. Additional details are provided on the more rare skin manifestations and noncutaneous findings that are easy to detect on physical

Noncutaneous manifestations

Key points

  1. Dermatologists should screen for bone abnormalities that may require referral to orthopedics.

  2. Learning disabilities are the most common complication in children with NF1.

NF1 has the ability to affect nearly every organ system. While this paper is focused on the cutaneous manifestations, consideration must also be given to findings that the dermatologist may note on a physical examination or gather from the patient's history so that appropriate steps may be taken. A summary of these findings is

Management and future directions

The dermatologist has a primary role in recognizing and differentiating NF1 from other conditions based on a careful skin examination, making appropriate referrals once the diagnosis is made, and managing symptomatic or disfiguring cutaneous neurofibromas. Currently, neurofibromas are amenable only to surgical removal. Symptomatic (ie, painful and bleeding) neurofibromas are most commonly removed but, depending on the community, this may not be handled by dermatology. Several studies have

Summary

NF1 is a multisystem disorder requiring management by multiple disciplines, often coordinated through a primary care physician or a geneticist. The dermatologist has a role not only in the diagnosis of NF1 and differentiating it from other similar disorders but also in the recognition of rare but associated skin manifestations. Genetic testing has increased our ability to make the diagnosis in uncertain cases, but has not allowed us to predict a particular patient's natural history based on the

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    Funding sources: None.

    Conflicts of interest: The authors, editors, and peer reviewers have no relevant financial relationships.

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