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 (NF1 and NF2)

The recommended management of neurofibromatosis requires a multidisciplinary approach with specialized NF clinics, regular surveillance for tumor development, and targeted interventions for symptomatic manifestations, with selumetinib being FDA-approved specifically for symptomatic, inoperable plexiform neurofibromas in pediatric NF1 patients. 1, 2

Neurofibromatosis Type 1 (NF1) Management

Regular Surveillance and Monitoring

• Annual general medical evaluation should include assessment for signs and symptoms of malignant peripheral nerve sheath tumors, pheochromocytoma, neuropathy, depression, chronic pain, and pruritus 1
• Blood pressure monitoring at each visit to screen for hypertension, which could indicate pheochromocytoma or renovascular disease 1
• Clinical evaluation for scoliosis with Adam's forward bend test and referral to orthopedics if scoliosis is suspected 1
• Consider baseline MRI of known or suspected nonsuperficial plexiform neurofibromas 1
• For women with NF1, annual mammogram starting at age 30 and consideration of breast MRI with contrast between ages 30-50 due to increased breast cancer risk 1

Management of 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
• Monitor for cardiomyopathy, ocular toxicity, gastrointestinal toxicity, skin toxicity, and increased creatine phosphokinase during treatment 2
• For adults with symptomatic plexiform neurofibromas, surgical intervention may be considered when tumors are causing significant symptoms or functional impairment 1

Management of Cutaneous Neurofibromas

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

Skeletal Manifestations

• Vitamin D supplementation is recommended to reach serum 25-hydroxyvitamin D concentrations in the sufficient range 1
• Treatment of osteoporosis in NF1 follows the same guidelines as for the general population 1
• Consider dual energy X-ray absorptiometry (DXA) to assess bone mineral density 1

Gastrointestinal Manifestations

• Adults with NF1 should follow general population age- and gender-specific health screening, including colonoscopy 3
• No specific GI imaging surveillance is recommended for asymptomatic patients 3
• For suspected gastrointestinal stromal tumors (GISTs), endoscopic ultrasound with biopsy is preferred 3

Neurofibromatosis Type 2 (NF2) Management

Hallmark Features and Surveillance

• Bilateral vestibular schwannomas are the defining feature of NF2 4
• Regular monitoring of hearing function and tumor growth with MRI is essential 4, 5
• Multiple meningiomas, ependymomas, and other central nervous system tumors are common in NF2 and require surveillance 4

Management Approaches for NF2

• Surgery is the primary clinical tool for management of vestibular schwannomas 4
• Early interventional surgery may help preserve hearing in some cases 4
• Cochlear implants or auditory brainstem implants are options for hearing loss 4
• Bevacizumab (a VEGF inhibitor) can prolong hearing and delay the need for surgery in patients with bilateral vestibular schwannomas 6

Special Considerations

Pregnancy and Family Planning

• Educate adults with NF1 that, as an autosomal dominant disorder, the offspring recurrence risk is 50% for each pregnancy 1
• Preimplantation genetic diagnosis (PGD) and prenatal diagnosis of NF1 are available options 1
• Referral to a high-risk obstetrician should be considered for pregnant women with NF1 1
• 52-60% of women report an increase in growth of neurofibromas during pregnancy 1

Mental Health and Quality of Life

• Consider screening for depression in adults with NF1, with appropriate referral 1
• The visibility of lesions is associated with negative effects on emotions, physical symptoms, and functioning 1

Clinical Pitfalls and Caveats

• Most common symptoms (hypertension, back pain, headaches) are usually not related to NF1 complications, but NF1-associated etiologies should always be considered 1
• In NF2, there is no correlation between vestibular schwannoma size and hearing loss, making clinical monitoring complex 4
• Vestibular schwannomas in NF2 grow faster than their sporadic counterparts 4
• Individuals with de novo mutations, somatic mosaicism, and large genomic rearrangements are much less likely to be able to have successful PGD due to technical limitations 1

Coordination of Care

• Evaluation by and care coordination with a specialized NF clinic is strongly recommended 1
• The multidisciplinary team should include specialists in medical genetics, neurology, ophthalmology, oncology, and other relevant specialties based on patient needs 1
• Patient education about worrisome signs and symptoms is essential for early detection of complications 1