Editing Neurofibromatosis (section)

== '''NF1''' ==

* Previously known as von Recklinghausen disease
* Hallmarks multiple café au lait macules and neurofibromas

Epidemiology: 

* Most common type of neurofibromatosis
* most common neurocutaneous & inherited tumour syndrome (1:3,000) 
* always presents <5yo 

Cause: 

* AD disorder (50% hereditary, 50% sporadic/ spontaneous) 
* Penetrance is complete
* Mutations of NF1 gene = chromosome 17 (q11.2) result in altered form of a protein, neurofibromin
* Caused by a loss of NF1 gene which normally functions as a tumour suppressor (mutation causes uncontrolled cell proliferation i.e. neurofibromas) 

Features and pathology: 

* Typical order is café au lait macules, axillary and/or inguinal freckling, Lisch nodules (iris hamartomas) and neurofibromas
* If present, osseous dysplasias usually appear by 1yo
* Symptomatic optic pathway glioma appears by 3yo
* Malignant peripheral nerve sheath tumours

NF-1 Diagnostic Criteria: 

* At least two (CAFE SPOT): (this mnemonic seems too good to be true but it actually quite accurate)
** C: cafe au lait spots (six or more is highly suggestive of NF1)
** A: axillary or inguinal freckles (Crowe sign)
** F: fibromas (neurofibroma (>2) or plexiform neurofibroma (1) 
** E: eye hamartomas (Lisch nodules - 2 or more) 
** S: skeletal abnormalities (sphenoid wing and occipital bone dysplasia, leg bowing from thinning of bone cortex, scoliosis) 
** P: positive FHx 
** OT: optic tumour (optic nerve glioma) or optic pathway glioma


Neoplasm risks:

* Malignant peripheral nerve sheath tumours (15%)
* Optic nerve pathway glioma (15%)
* Brain/spinal cord glioma (3%)
* Breast cancer (20-40% lifetime)
* Phaeochromocytoma (2%)
* GIST (6%)
* NET (1.5%)


Surveillance

* Breast cancer - start annual MRI aged 30
* Phaeochromocytoma - annual BP measurement and low threshold for testing biogenic amines
* Malignant peripheral nerve sheath - annual clinical exam