Clinical Presentations of Neurofibromatosis Type 1 (NF1)
Neurofibromatosis type 1 (NF1) most commonly presents with cutaneous manifestations including café-au-lait macules and multiple cutaneous neurofibromas, which are present in >99% of adults with the condition. 1
Key Diagnostic Features
Cutaneous Manifestations
- Café-au-lait macules: Light brown patches on the skin that typically appear in early childhood
- Cutaneous neurofibromas (cNF): Present in >99% of adults with NF1 1
- Begin to appear during puberty
- Continue to increase in number with age
- Show periods of rapid growth during puberty and pregnancy
- May be symptomatic (tenderness, bleeding, itching)
- Axillary and inguinal freckling: Characteristic small pigmented spots
Ocular Findings
- Lisch nodules: Iris hamartomas that appear as dome-shaped elevations on the iris
- Choroidal nodules: Present in the back of the eye
- Orbital-periorbital plexiform neurofibromas (OPPN): Can cause:
- Proptosis
- Ptosis
- Facial disfigurement
- Vision loss due to amblyopia or glaucoma 1
Skeletal Manifestations
- Scoliosis: Two types 1
- Dystrophic: Typically presents in childhood with rapid progression
- Nondystrophic: Can develop into adulthood
- Long bone dysplasia/pseudarthrosis: Particularly affecting the tibia
- Sphenoid wing dysplasia
- Decreased bone mineral density and osteoporosis: Occurs at an earlier age than the general population 1
Neurological Manifestations
- Plexiform neurofibromas (PN): Complex nerve sheath tumors that follow multiple nerve branches
- Most diagnosed in early childhood
- May demonstrate rapid growth during childhood
- Risk for malignant transformation 1
- Headaches and migraines: More common in NF1 patients than the general population 1
- Seizures: Higher prevalence than general population
- Sleep disturbances: Common in adults with NF1 1
- NF1 neuropathy: A rare (2-3%), adult-onset, non-progressive, symmetrical polyneuropathy 1
Pain Syndromes
- Glomus tumors: Small, benign but painful tumors in fingertips 1
- Chronic pain: Common and can negatively affect quality of life
- May be nociceptive or neuropathic
- Can arise from plexiform neurofibromas, scoliosis, or pseudarthrosis
- New-onset, increasingly severe pain should be evaluated for possible malignant peripheral nerve sheath tumor (MPNST) 1
Age-Related Presentation Patterns
Childhood
- Café-au-lait macules (typically first sign)
- Development of plexiform neurofibromas
- Dystrophic scoliosis
- Long bone dysplasia/pseudarthrosis
Adolescence/Puberty
- Appearance of cutaneous neurofibromas
- Increased growth of existing neurofibromas
Adulthood
- Progressive increase in number of cutaneous neurofibromas
- Development of nondystrophic scoliosis
- Earlier onset osteoporosis
- Potential malignant transformation of plexiform neurofibromas
Pregnancy
- Increased size and number of neurofibromas
- 33-60% of women experience growth of existing neurofibromas
- 52-60% develop new neurofibromas 1
Impact on Quality of Life
Visibility of NF1 lesions is associated with significant negative effects on:
- Emotional well-being
- Physical symptoms
- Daily functioning 1
Clinical Pitfalls to Avoid
Failure to recognize NF1-associated pain: Not all pain in NF1 patients is due to neurofibromas; evaluate for common causes but be vigilant about new or progressive pain that could indicate malignant transformation 1
Overlooking osteoporosis: NF1 patients develop osteoporosis at an earlier age; consider earlier screening with DXA 1
Missing scoliosis progression: Regular monitoring for curve progression is essential, as approximately 50% of those with childhood-diagnosed scoliosis show progression into adulthood 1
Delayed diagnosis of glomus tumors: These painful fingertip tumors are often missed, leading to years of unnecessary pain 1
Underestimating impact on quality of life: The cosmetic burden of neurofibromas can significantly affect emotional well-being and social functioning 1