Neurofibromatosis Type 1: The Reality Behind the Diagnosis

Written by: Jacob Silverman

Reviewed by: Tiffany Chen, Katie Kugler, and Ethan Bendayan

Introduction

Despite earlier reports of similar cases in history, it was Von Recklinghausen who was credited with first describing the condition we now know as neurofibromatosis type 1 (NF1) in 1882. NF1 is one of the most common autosomal dominant diseases, and affects approximately 1/2500–3000 individuals. An affected parent therefore has a 50% chance of passing it on to their children, but spontaneous mutations are possible even without a family history.

Neurofibromatosis is subclassified classified into type 1 and type 2. Both involve tumour suppressor genes, albeit completely different ones with different mechanisms, thus the shared nomenclature is more historical. These conditions both predispose the individual to nervous system tumours of different varieties depending on the subtype of NF.

NF1 specifically involves the NF1 gene on chromosome 17, which produces the protein neurofibromin, a tumour suppressor gene, as mentioned, meaning it keeps cell growth in check. In other words, it prevents the cell from uncontrollably dividing and eventually causing cancer. And so, when there is a problem in this gene, nothing prevents the cell from growing out of control, leading to the increased tumour risk mentioned.

In this article, we will focus primarily on NF1 as it is the subtype with the most significant dermatological features.

Signs and Symptoms

NF1 has many clinical manifestations. From most to least frequent, they are: Café au lait macules, cutaneous neurofibromas, Lisch nodules, choroidal abnormalities, intertriginous freckling, learning difficulties, behaviour issues, plexiform neurofibromas, osteoporosis, hypertension, optic pathway glioma, nodular neurofibromas, malignant peripheral nerve sheath tumour, seizures, scoliosis, intellectual disability, non-optic glioma, and long bone dysplasia.

While we cannot cover every feature in depth, this article will focus on some of the most common dermatological symptoms found in NF1.

Café au lait macules (flat spots in the colour of coffee with milk) are not unique to NF1, but are a hallmark symptom, with affected individuals often having more than six. They can continue to develop and grow over time.

Neurofibromas may be cutaneous (arising from the skin) or subcutaneous (located beneath the skin). They are small bumps that are actually tumours of peripheral nerve support cells (Schwann cells) and can appear anywhere in the body. They are more common in adults with NF1 and are largely asymptomatic except for reported itchiness and tenderness.

Intertriginous (in folds of skin) freckling usually appears in children and signifies presence of freckles in the armpit or groin of an affected child.

Finally, while not truly dermatological, Lisch nodules are growths on the iris that appear in adolescence. They can be seen without magnification and may be clear/yellow or brown. They are not known to be associated with any ophthalmological complications.

While not all are necessary for a diagnosis, all of these dermatological signs are part of the diagnostic criteria for NF1.

Treatments

Unfortunately, NF1 currently has no cure yet. Current management involves regular screening to detect signs and symptoms, especially if the patient has a known family history. It is beneficial for patients to be seen by specialists if there is a risk, even if symptoms have not yet appeared.

Specific symptoms may be treated with medications or surgery. Additionally, learning disabilities like ADHD or developmental delay can be supported through various disciplines to ensure the success of the child at school.

Regarding the dermatological symptoms previously mentioned, some medications (e.g., ketotifen) have been studied but have little-to-no effect. Various interventions exist for cutaneous neurofibromas, which, as we will explore below, are the most burdensome feature of NF1. These include surgical removal and various types of laser destruction (carbon dioxide or Er:YAG, different properties). Each of these methods come with their own risks and benefits. For instance, surgery yields cosmetically appealing outcomes, while posing the risk of anesthesia and only being able to deal with a few neurofibromas at a time. Carbon dioxide laser, on the other hand, can target multiple neurofibromas at once, but may leave behind discoloration. The more contemporary lasers like Er:YAG offer many advantages but also pose a greater bleeding risk.

However, especially considering its single-gene source, NF1 seemingly may be a good candidate for future genetic therapy. Indeed, very recently in October 2025, a Johns Hopkins team developed a new targeted gene therapy strategy using a virus to correct the DNA defect. This would, in essence, correct the problem at the very source. While this would hopefully reduce dermatological-associated burden, it would also reduce risk of the rare aggressive cancers that may present in NF1. The treatment landscape is rapidly changing for NF1, with targeted therapies showing significant benefit.

Psychosocial impact

Due to the physical disfigurement common with NF1, research has tackled the psychosocial impact of this disease. In one study, children with increased NF1 severity and visibility were found to have a decreased physical and social quality of life. Their parents also noticed a reduction in their school functioning.  Additionally, another study found that these children were more at risk of victimization behaviours, coupled with depressive and anxious symptoms and reduced self-esteem. Altogether the researchers termed this a “maladaptive loop” of behaviours and a sense of vicious cycle where the victimization worsens the mental health side.

Not only is the mental health impact of this disease in the depressive sphere, but some researchers found that a significant proportion of children scored in the clinically significant ranges in the spheres of somatization, attention problems, and withdrawal as well.

Ressources

Thankfully, support communities exist, and platforms like SkinPact can help raise awareness and build acceptance.

Nathan Turgeon is a young Quebecois man affected by NF1 who speaks about his journey with the condition, the challenges he faces, and the impact it has had on him. Read more here: Thriving on and off the ice as a teenager living with a rare condition.

Key Takeaways

NF1 is a hereditary condition, mainly characterized by skin changes and masses whose impact and appearance can negatively impact a child’s psychosocial wellbeing. It is our hope that in better understanding this condition, a greater awareness and acceptance will build. Hopefully, the future will bring us interventions that will be able to effectively treat the condition, and especially its more dangerous outcomes.

Works Cited

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