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

Management of Neurofibromatosis

Neurofibromatosis requires specialized multidisciplinary care through dedicated NF clinics, with distinct surveillance and treatment strategies for NF1 versus NF2, and selumetinib (KOSELUGO) is FDA-approved for symptomatic, inoperable plexiform neurofibromas in pediatric NF1 patients aged 2 years and older. 1, 2

Neurofibromatosis Type 1 (NF1) Management

Surveillance and Monitoring

Annual comprehensive evaluations should specifically assess for:

• Malignant peripheral nerve sheath tumors, pheochromocytoma, neuropathy, depression, chronic pain, and pruritus 1
• Blood pressure measurement at every visit to detect hypertension from pheochromocytoma or renovascular disease 1
• Scoliosis screening using Adam's forward bend test with orthopedic referral if abnormalities detected 1
• Baseline MRI of known or suspected nonsuperficial plexiform neurofibromas 1

Bone health monitoring includes:

• Dual energy X-ray absorptiometry (DXA) to assess bone mineral density 1
• Vitamin D supplementation to achieve sufficient serum 25-hydroxyvitamin D concentrations 1
• Standard osteoporosis treatment protocols when indicated 1

Cancer surveillance for women with NF1:

• Annual mammography starting at age 30 (not 40 as in general population) 1
• Breast MRI with contrast between ages 30-50 due to elevated breast cancer risk 1

Treatment Options

For symptomatic, inoperable plexiform neurofibromas in pediatric patients:

• Selumetinib (KOSELUGO) 25 mg/m² orally twice daily is the FDA-approved targeted therapy 2
• Dosing is weight-based according to body surface area, ranging from 20 mg/10 mg split dosing for BSA 0.55-0.69 m² up to 50 mg twice daily for BSA ≥1.90 m² 2
• Treatment continues until disease progression or unacceptable toxicity 2

For cutaneous neurofibromas:

• Surgical excision, laser removal, or electrodesiccation based on clinical judgment and patient preference 1

Critical Monitoring for Selumetinib Therapy

When using selumetinib, mandatory surveillance includes:

• Cardiac monitoring: Assess ejection fraction before treatment initiation, every 3 months during year one, then every 6 months thereafter 2
• Ophthalmologic assessments: Regular eye examinations to detect retinal pigment epithelial detachment or retinal vein occlusion 2
• Creatine phosphokinase (CPK): Baseline and periodic monitoring for rhabdomyolysis risk 2
• Bleeding risk awareness: Capsules contain vitamin E; avoid concurrent vitamin K antagonists or antiplatelet agents when possible 2

Dose modifications for adverse reactions:

• Withhold and reduce dose for asymptomatic LVEF decrease ≥10% from baseline 2
• Permanently discontinue for symptomatic decreased LVEF, Grade 3-4 LVEF decrease, or retinal vein occlusion 2
• Withhold until resolution then resume at reduced dose for retinal pigment epithelial detachment 2

Neurofibromatosis Type 2 (NF2) Management

Defining Features and Surveillance

Bilateral vestibular schwannomas are the pathognomonic feature of NF2 and require:

• Regular MRI monitoring for tumor growth 1, 3
• Serial hearing function assessments 1
• Surveillance for multiple meningiomas, ependymomas, and other CNS tumors 1, 3

Treatment Approaches

Surgery remains the primary management tool for vestibular schwannomas 1, 3:

• Early interventional surgery may preserve hearing in select cases 1, 3
• Significant surgical morbidity includes deafness and facial nerve dysfunction 3

Hearing rehabilitation options:

• Cochlear implants for appropriate candidates 1, 3
• Auditory brainstem implants when cochlear implants are not feasible 1, 3

Clinical Pitfalls in NF2

Critical caveat: Vestibular schwannoma size does NOT correlate with hearing loss in NF2, complicating clinical decision-making 3. Additionally, NF2-associated vestibular schwannomas grow faster than sporadic tumors 3.

Genetic Counseling and Reproductive Considerations

Both NF1 and NF2 are autosomal dominant with 50% recurrence risk for each pregnancy 1:

• Preimplantation genetic diagnosis (PGD) and prenatal diagnosis are available 1
• Pregnant women with NF1 should be referred to high-risk obstetrics 1
• Depression screening should be considered in adults with NF1 with appropriate mental health referral 1

Coordination of Care

Specialized NF clinic evaluation and care coordination is strongly recommended 1:

• Multidisciplinary teams should include medical genetics, neurology, ophthalmology, and oncology specialists 1
• Patient education about warning signs enables early complication detection 1
• The complex, variable nature of both disorders necessitates coordinated multidisciplinary management 4