What is the recommended management and treatment for neurofibromatosis (NF), including neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2)?

Management and Treatment of Neurofibromatosis (NF)

The recommended management for neurofibromatosis requires a multidisciplinary approach coordinated through specialized NF clinics, with regular monitoring for specific complications and targeted interventions for symptomatic manifestations. 1

General Management Principles

• Both NF1 and NF2 require regular surveillance and coordinated care through specialized neurofibromatosis clinics to monitor for disease progression and complications 1
• Annual comprehensive evaluations should assess for signs of tumor development, malignant transformation, and other NF-related complications 1
• Patient education about worrisome symptoms such as progressive severe pain, changes in tumor volume, new neurological symptoms, and diaphoresis/palpitations is essential 1

Management of Neurofibromatosis Type 1 (NF1)

Regular Monitoring

• Annual medical evaluation should include assessment for:

  • Signs/symptoms of malignant peripheral nerve sheath tumor (MPNST)
  • Pheochromocytoma
  • Neuropathy
  • Depression
  • Chronic pain and pruritus 1

• Physical examination should include:

  • Blood pressure measurement
  • Clinical evaluation for scoliosis with Adam's forward bend test 1

• Imaging recommendations:

  • For women: Annual mammogram starting at age 30
  • For women: Consider breast MRI with contrast between ages 30-50
  • Baseline MRI of known or suspected plexiform neurofibromas
  • Consider bone density testing based on clinical presentation 1

Treatment of NF1 Manifestations

Cutaneous Neurofibromas

• Treatment options include surgical excision, laser removal, or electrodesiccation based on physician expertise and patient preference 1
• All three therapies have shown minimal scarring, minor discomfort, and high patient satisfaction 1
• General anesthesia may be required for removal of multiple lesions 1

Plexiform Neurofibromas

• Selumetinib (Koselugo) is FDA-approved for pediatric patients 2 years and older with symptomatic, inoperable plexiform neurofibromas 2
• The recommended dosage is 25 mg/m² orally twice daily until disease progression or unacceptable toxicity 2
• Monitoring for adverse effects is essential, including cardiomyopathy, ocular toxicity, gastrointestinal toxicity, and skin reactions 2

Skeletal Manifestations

• Vitamin D supplementation is recommended for individuals with NF1 to maintain sufficient serum levels 1
• Management of scoliosis consists of monitoring for curve progression with annual clinical evaluation 1
• Osteoporosis treatment follows general population guidelines but should be initiated earlier due to increased risk 1

Management of Neurofibromatosis Type 2 (NF2)

Regular Monitoring

• The hallmark of NF2 is bilateral vestibular schwannomas (VS) which require regular monitoring 1
• Regular imaging surveillance is essential to track tumor growth and plan interventions 1

Treatment Approaches

Vestibular Schwannomas

• Surgery remains the primary clinical tool for NF2 management 1
• Early interventional surgery may preserve hearing in some patients 1
• Candidates for cochlear preservation surgery include patients with VS ≤1.5 cm in diameter and speech discrimination scores ≥70% 1

Hearing Preservation

• Cochlear implants may benefit patients with preserved cochlear nerve function 1
• Auditory brainstem implants are options for patients who have lost cochlear nerve function 1

Special Considerations

Pregnancy in NF1

• Contraception should be used if pregnancy is not desired 1
• Referral to a high-risk obstetrician should be considered for pregnant women with NF1 1
• 52-60% of women report increased growth of neurofibromas during pregnancy 1

Genetic Counseling

• NF1 and NF2 are autosomal dominant disorders with 50% offspring recurrence risk 1
• Preimplantation genetic diagnosis and prenatal diagnosis are available options 1
• Individuals with de novo mutations, somatic mosaicism, and large genomic rearrangements may have technical limitations for preimplantation genetic diagnosis 1

Common Pitfalls and Caveats

• Not all symptoms in NF patients are related to their NF; common conditions remain common (e.g., most hypertension is not pheochromocytoma-related) 1
• Regular monitoring should continue even during periods of apparent disease stability, as tumors can have periods of dormancy followed by growth 1
• Specialized NF clinics provide the most comprehensive care and access to clinical trials of novel therapies 1
• Patients should be educated about warning signs requiring urgent evaluation, including progressive severe pain, changes in tumor volume, and new neurological symptoms 1