Clinical Guidance
Neurofibromatosis 1 (NF1) is an extremely variable multisystem disease; the progression and severity may differ throughout life in an affected individual as well as in affected family members with the same NF1 pathogenic variant . The cardinal clinical manifestations of NF1 include multiple caf au lait macules, intertriginous freckling, multiple cutaneous neurofibromas, subcutaneous or deep nodular neurofibromas, plexiform neurofibromas, and characteristic ocular signs. Problems with learning, behavior, and social adaptation are unusually common among people with NF1. Optic or non-optic gliomas occur much more often than expected, but most of these tumors exhibit a benign course. Individuals with NF1, especially those with plexiform or deep nodular neurofibromas in large numbers or of large size, are at high risk of developing malignant peripheral nerve sheath tumors, which tend to occur at a much younger age and have a worse prognosis than in the general population. Women with NF1 are at increased risk of developing breast cancer and have complications of pregnancy more often than expected. Hypertension is frequent in people with NF1, and NF1 vasculopathy may cause stroke or other cardiovascular complications in affected children and young adults. Vertebral or tibial dysplasia can cause major disability in some individuals, and NF1-associated gastrointestinal, endocrine, or pulmonary disease – although less frequent – may be quite serious. Table 2. Neurofibromatosis 1: Frequency of Select Features
Feature | % of Persons w/Feature1 | Typical Age of Onset | Comment |
|---|
Caf au lait macules | 99% | Infancy childhood | in number size during 1st few yrs of life; macules fade in older persons. |
Intertrigenous freckling | 85% | Infancy early childhood | Frequency w/age during childhood. |
Lisch nodules | 95% | Early childhood | Frequency w/age during childhood. |
Choroidal abnormalities | 82%-98% | Early childhood | in number size during childhood |
Optic pathway glioma | 15%-20% | Birth - 6 yrs | Frequency lower in adults |
Non-optic glioma | 2%-5% | Any age | Frequency lower in children than adults |
Cutaneousneurofibromas | 99% | Adolescence-adulthood | Infrequent in childhood; variably in size number throughout life |
Nodular neurofibromas (subcutaneous or deep) | ~15% | Adolescence | Frequency shown is on clinical exam; frequency is 2-3x higher on whole-body MRI. |
Plexiformneurofibroma(s) | ~30% | Infancy (sometimes congenital) or childhood | Frequency shown is on clinical exam; frequency is ~50% on whole-body MRI. |
Malignant peripheralnerve sheath tumor | 8%-13% | Adolescence - adulthood | Cross-sectional prevalence 2%-5% after mid-childhood |
Intellectual disability | 4%-8% | Childhood | Persists throughout life |
Learning difficulties | 50%-60% | Childhood | Persist throughout life |
Behavior issues | 30%-67% | Childhood | — |
Seizures | 6%-7% | Any age | — |
Long bone dysplasia | 2% | Infancy (congenital) | — |
Dystrophic scoliosis | 5% | 6-10 yrs | Rapidly progressive scoliosis due to vertebral dysplasia |
Nondystrophic scoliosis | 5% | Adolescence | Milder scoliosis w/o vertebral anomalies |
Osteoporosis | ~20% | Mid-adulthood | Osteopenia is frequent at all ages; osteoporosis occurs earlier than in general population but is rare in children uncommon in young adults |
Hypertension | ≥15%-20% | Any age | Prevalence greater in adults than children Many of the features listed in this table have different frequencies at different ages. The table gives life-time cumulative incidence figures that may be higher, and sometimes much higher, than the prevalence at any given age. |
Source: GeneReviews — "Neurofibromatosis 1"
