Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that is characterized by cutaneous findings, most notably café-au-lait spots and axillary freckling (see the images below), by skeletal dysplasias, and by the growth of both benign and malignant nervous system tumors, most notably benign neurofibromas.
Signs and symptoms
Signs and symptoms of NF1 can vary widely from patient to patient. The earliest clinical finding usually seen in children with NF1 is multiple café-au-lait spots. These may be present at birth or may appear over time, frequently increasing in size and number throughout childhood.
Axillary or inguinal freckles are rarely present at birth, but appear during childhood through adolescence. Subcutaneous or cutaneous neurofibromas are seen rarely in young children but appear over time in older children, adolescents, and adults.
Other signs and symptoms may include the following:
- High blood pressure (potentially from renal artery stenosis or pheochromocytoma)
- Bone abnormalities
- Optic nerve tumors
- Lisch nodules
- Learning disabilities; Attention deficit hyperactivity disorder; Autism spectrum disorder
- Larger than average head size
- Short stature
Diagnosis
Clinical diagnosis requires the presence of at least 2 of 7 criteria to confirm the presence of NF1. Many of these signs do not appear until later childhood or adolescence; thus, confirming the diagnosis often is delayed despite a suspicion of NF1. The 7 clinical criteria used to diagnose NF1 are as follows, in the absence of alternative diagnoses:
- Six or more café-au-lait spots or hyperpigmented macules greater than 5 mm in diameter in prepubertal children and greater than 15 mm postpubertal
- Axillary or inguinal freckles (>2 freckles)
- Two or more typical neurofibromas or one plexiform neurofibroma
- Optic nerve glioma
- Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist
- Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis
- First-degree relative (eg, mother, father, sister, brother) with NF1
Management
Medical care
There is no cure for neurofibromatosis. Patients should be routinely monitored for complications. Annual examinations should include the following:
- Assessment of skin to look for new neurofibromas or progression of existing lesions
- Check of blood pressure
- Evaluation of growth and development
- A complete eye exam
- Evaluation of skeletal changes and abnormalities
- Assessment of learning development
Chemotherapy, radiation therapy, or both may be used to treat cancerous tumors, but with the avoidance of radiation therapy when possible, due to the incurred increased risk of secondary malignancies.
Surgical care
Surgery can be used to remove tumors that cause pain or a loss of function. Neurofibromas that press on vital structures, obstruct vision, or grow rapidly deserve immediate attention.
Orthopedic intervention is indicated for rapidly progressive scoliosis and for some severe bony defects.
