Neurofibromatosis

DEFINITION

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EPIDEMIOLOGY
Type I is relatively common at 1:3000.

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AETIOLOGY
Two AD genetic IEMs.
Type I: von Recklinghausen Disease
- 50% new mutations.
- expressivity very variable, but penetrance of 100%.
- most of the below relates to type 1
Type II: acoustic neurofibromatosis
- just 1:40-50,000
- NF2 gene on chromosome 22q12.

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BIOLOGICAL BEHAVIOUR

Pathophysiology
The NF1 gene on 17q11.2, encodes neurofibromin, which down-regulates p21 ras oncoprotein function
- hence belongs to the family of tumour-suppressor genes.
In neurofibromas (see below), all the elements of nerve tissue are proliferated.
- dispersed in a loose disorderly fashion.
- the plexiform variety (below) can become malignant in 5%.
- the superficial lesions rarely become malignant.
In Type II, they develop bilateral acoustic schwannomas and multiple meningiomas.
- also nodular ingrowth of non-neoplastic cells, eg Schwann cells into the cord, meningioangiomatosis into brain etc.
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MANIFESTATIONS

Principle Features

Type I

1. Multiple neural tumours (neurofibromas) widely dispersed.
- if cutaneous, are soft, sessile or pedunculated.
- subcut tumours are firm round and often painful.
- skin / subcut tumours can be from 1 - 20cm huge pendulous masses.
- or 'plexiform neurofibroma', thickened toruous nerves, with overling hyperpigmented skin.

2. Numerous pigmented skin lesions (including cafe au lait spots)
- found in 90% or more.
- normal people may have a few, but six or more >1.5 cm makes the diagnosis likely.

3. Pigmented iris hamartomas (Lisch nodules)
- 94% or people over the age of 6
- symptomless but help in diagnosis.

Associated Abnormalities
Skeletal: erosive lesions (bone neurofibromas), scoliosis, cystic lesions, subperiosteal bone cysts, pseuroarthrosis of the tibia.
Other tumours: 2-4x risk, eg Wilm's rhabdomyosarcomas, meningiomas, optic gliomas, phaeochromocytomas, CML.
Cognitive: some have normal IQ, but most reduced intelligence.
GI: obstruction or bleeding if neurofibromas occur in the gut.
Renal: hypertension (arterial blockage)
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INVESTIGATIONS
Largely a clinical diagnosis.
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MANAGEMENT
As per specific defect being treated.
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REFERENCES
Robbins Pathology.