Neurofibromatosis
NF1
Autosomal
dominant
Loss
of function mutation of NF1 tumour suppressor gene
o
Ras MAP kinase pathway
1/1900-1/3500 people
Variable severity of disease between and within family
Can ne mosaic
Clinical
Nerve sheath tumours
Plexiform neurofibromas
MPNST
Skin changes
Cafι-Au
Lait spots hyperpigmented macules or patches seen in various regions in the
body
Freckling hyperpigmented areas smaller in size than cafι-au lait spots most prominent in the axillary and inguinal regions
Occular changes
Lisch
Nodules pigmented iris hamartomas. Benign, elevated, tan-colored
iris nodules.
Optic nerve glioma (see below)
Malignancy
Malignant peripheral nerve sheath tumour
evolve from plexiform neurofibroma (benign congenital lesion affecting 50%)
Screening
for Malignant Peripheral Nerve Sheath Tumours MPST - HELP
o
Hardness
o
Enlarging
o
Limb numbness or weakness
o
Pain
Breast cancer 3.5x risk
Pheochromocytoma
Slightly increased risk of a number of other cancers
Optic nerve glioma
- 15-20% of patients
- 30-50% of these will be symptomatic
- Rarely develop after the age of 7
- Surgical treatment rarely an option
- Rarely radiation
- Chemotherapy can be considered
Hypertension
Essential hypertension and secondary to pheochromocytoma
Bone health
Osteoporosis high incidence
Bone dysplasia
Neurocognitive and Psychiatric
Depression
ADHD
Cognitive impairment occurs at higher rate in NF1
Pain
Headache
Peripheral neuropathy
Fingertip pain (glomus body)
Vasculopathy / Moya moya
Screening checklist (EviQ, 2026)
Treatment
Mek inhibitors for plexiform neurofibromas
- Selumetinib
-
Trametinib
-
Mirdametinib
- SE:
Skin toxicity
NF2
Autosomal dominant
However mosaicism common
>50% are first in family
Mosaicism common
Clinical
o Vestibular schwannoma, often bilateral
o Meningioma
o Ependymoma
o
Early-onset cataracts usually bilateral
Decreased life expectancy
Treatment of VS
Surgery often results on hearing loss
If hearing already lost then surgery may be best option
If hearing preserved consider radiation Bevacizumab, Brigatinib
References
· ACMG Practice guidelines Care of adults with NF1 Genetics in Medicine 2018