TABLE 2

Evaluation and Management for Features of NF1

NF1 Diagnostic FeatureEvaluationManagement
Café-au-lait maculesEarly diagnostic feature (0–2 years of age): hyperpigmented macules, typically ranging from 1.0 to 3.0 cm in diameterNo evidence supporting laser therapy for removal; cosmetic advice can be given on skin camouflaging
Skinfold frecklingDiagnostic feature (3–5 y of age): freckling in axillary and inguinal areas most common, with freckling sometimes extending beyondNo follow-up necessary
Lisch nodulesDiagnostic feature: pigmented iris hamartomas on slit-lamp examinationRefer to ophthalmologist
Cutaneous neurofibromaDiagnostic feature (childhood or early adolescence): benign peripheral nerve sheath tumors; may present with localized pruritusSurgical removal for lesions causing pain or cosmetic disfigurement depending on size and location; carbon-dioxide laser therapy may be helpful for removing small superficial lesions; after removal of lesions, patients are at risk for recurrence, hypertrophic scarring, and neurologic deficit
Plexiform neurofibromaDiagnostic feature: peripheral nerve sheath tumors involving multiple nerve fascicles; may extend into surrounding structures with varying growth rates and patterns; deep lesions may only be detected on radiologic examinationRegular follow-up with special attention given to signs and symptoms of transformation to MPNST; FDG-PET may distinguish benign plexiform neurofibromas from MPNSTs; surgical excision for symptomatic tumors; radiotherapy is contraindicated
MPNSTsOften arise from preexisting plexiform neurofibromas; consult an NF1 specialist for persistent pain for >1 mo or pain that disrupts sleep, new or unexplained neurologic deficit (alteration in neurofibroma texture from soft to hard), or rapid increase in neurofibroma sizeComplete resection with tumor-free margins is ideal; however, tumor location dictates surgery; adjuvant radiotherapy is useful for partially resectable, aggressive, or >5-cm tumors; benefit of chemotherapy as second adjuvant remains controversial; regular (every 3–4 months) follow-up for metastases (ie, chest computer tomography scans, bone pain follow-up)
Skeletal dysplasiaClinicians should be aware of a range of issues including scoliosis, congenital bone defects leading to pseudoarthroses, sphenoid wing dysplasia, macrocephaly, and short stature; closely follow linear growth curves and skeletal parametersScoliosis may require use of a brace, corrective surgery, or spinal fusion depending on severity; pseudoarthroses typically respond poorly to surgery and amputation may be necessary, although early bisphosphonate therapy maybe beneficial
OPGMRI for visual or endocrinologic signs and symptomsMRI at 3- to 12-mo intervals with regular neuroophthalmologic and endocrinologic evaluations; standard chemotherapy includes carboplatin and vincristine; radiotherapy is contraindicated
Neurocognitive deficitsObtain developmental and neuropsychological assessments before beginning schoolDevelop an individual education plan (IEP); obtain yearly assessments and follow with a special educational needs coordinator
Cardiovascular abnormalitiesAnnual blood pressure screening and heart examinationRenal arteriography and 24-h urinary excretion of total plus fractionated catecholamines and metabolites for high blood pressure; refer patients with murmurs to cardiology
  • Adapted from refs 79, 11, 16, 22, 24, 25, 27, 28, 35, 36, 39, 42, and 45.