What are the symptoms and complications of Neurofibromatosis Type One (NF1)?

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From the Guidelines

Neurofibromatosis Type One (NF1) is a genetic disorder that presents with a variety of symptoms and potential complications, including malignant peripheral nerve sheath tumors, breast cancer, cutaneous neurofibromas, and significant psychiatric and neurologic diagnoses, as reported in a 2018 study published in Genetics in Medicine 1. The symptoms and complications of NF1 can affect multiple body systems, and the hallmark symptoms include:

  • Café-au-lait spots (light brown patches on the skin)
  • Freckling in the armpits or groin
  • Neurofibromas (small benign tumors on or under the skin)
  • Lisch nodules (pigmented spots on the iris) Children with NF1 often develop these signs progressively, with café-au-lait spots typically appearing first, sometimes at birth or in early infancy. Other common manifestations of NF1 include:
  • Skeletal abnormalities like scoliosis, tibial bowing, or pseudarthrosis (false joints)
  • Learning disabilities, attention deficit hyperactivity disorder, and speech problems, which affect approximately 50-60% of individuals with NF1
  • Optic pathway gliomas (tumors affecting vision)
  • Plexiform neurofibromas (larger, more diffuse tumors that can cause disfigurement)
  • Hypertension
  • Malignant peripheral nerve sheath tumors, which are rare but serious complications of NF1 According to a 2024 study published in Clinical Cancer Research, children with NF1 are at significantly increased risk of benign and malignant neoplasms, and regular monitoring by a multidisciplinary team is essential for early detection and management of these complications 1. The management of NF1 typically involves regular monitoring by a multidisciplinary team, with treatment directed at specific complications as they arise rather than the condition itself. It is essential to prioritize the single most recent and highest quality study when making a definitive recommendation, and in this case, the 2024 study published in Clinical Cancer Research provides the most up-to-date guidance on the management of NF1 1.

From the Research

Symptoms of Neurofibromatosis Type One

  • Café-au-lait macules, skinfold freckling, and Lisch nodules are common pigmentary lesions found in nearly all individuals with NF1 2
  • Dermal neurofibromas are also common in individuals with NF1 2
  • Learning disabilities, attention deficits, and social and behavioural problems can occur in individuals with NF1 3, 2
  • Skeletal abnormalities such as scoliosis, tibial pseudarthrosis, and orbital dysplasia can occur in individuals with NF1 3, 2
  • Brain tumours such as optic pathway gliomas and glioblastoma can occur in individuals with NF1 3, 2
  • Peripheral nerve tumours such as spinal neurofibromas, plexiform neurofibromas, and malignant peripheral nerve sheath tumours can occur in individuals with NF1 3, 2

Complications of Neurofibromatosis Type One

  • Optic pathway glioma (OPG) can occur in up to 10% of individuals with NF1 4
  • Macrocephaly can occur in up to 36% of individuals with NF1 4
  • Hydrocephalus can occur in up to 5% of individuals with NF1 4
  • Retardation can occur in up to 14% of individuals with NF1 4
  • Brain tumours can occur in up to 5% of individuals with NF1 4
  • Kyphoscoliosis can occur in up to 13% of individuals with NF1 4
  • Renal artery stenosis can occur in up to 0.5% of individuals with NF1 4
  • Neurofibrosarcoma can occur in up to 0.5% of individuals with NF1 4
  • Malignant peripheral nerve sheath tumours can be life-threatening and occur in some individuals with NF1 5
  • Chronic pain can be a leading symptom in adults with NF1, related to malignant peripheral nerve sheath tumours, complications of intraspinal neurofibromas, subcutaneous neurofibromas, and peripheral nerve neurofibromas 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Neurofibromatosis type 1.

Nature reviews. Disease primers, 2017

Research

Clinical and genetic aspects of neurofibromatosis 1.

Genetics in medicine : official journal of the American College of Medical Genetics, 2010

Research

[Neurofibromatosis type 1: a survey of 195 patients].

Nederlands tijdschrift voor geneeskunde, 1997

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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