Neurofibromatosis/tuberous Sclerosis Flashcards
What is neurofibromatosis?
This is a genetic condition which causes nerve tumours (neuromas) to develop throughout the NS.
Where is the neurofibromatosis 1 gene found? What does it code for?
This is found on chromosome 17
It codes for a protein called neurofibromin, this is a tumour suppressor protein
What pattern of inheritance is mutation of the NF1 gene (found on chromosome 17)?
Autosomal dominant
What is the diagnostic criteria for neurofibromatosis?
There are clear diagnostic criteria for NF1 based on the classical features of the condition
There must be at least 2 of the 7 features to indicate a diagnosis
You can remember the features with CRABBING
C= cafe au lait spots (6 or more) R= relative with NF1 A= axillary or inguinal freckles BB= bony dysplasia (bowing of a long bone or sphenoid wing dysplasia) I= iris hamartomas (lisch nodules) yellow brown spots on the iris N= neurofibromas (2 or more) or 1 pelxiform neurofibroma G= glioma of the optic nerve
What do bilateral acoustic neuromas indicate?
Bilateral acoustic neuromas almost certainly indicate neurofibromatosis type 2
Where is the defective gene in neurofibromatosis type 2 found and what does it code for?
The neurofibromatosis type 2 gene is found on chromosome 22. It codes for a protein called merlin, which is a tumour suppressor protein particularly important in Schwann cells. Mutations in this gene lead to the development of schwannomas (benign nerve sheath tumours of the Schwann cells). Inheritance is autosomal dominant.
What are the symptoms of an acoustic neuroma?
- hearing loss, tinnitus, balance problems
What are the complications of neurofibromatosis type 1?
Migraines Epilepsy Renal artery stenosis Leukaemia ADJd Malignant peripheral nerve sheath tumours GI stromal tumours Spinal cord tumours Brain tumours Increased risk of cancer
What is tuberous sclerosis?
A genetic condition which causes features in multiple systems, the characteristic feature is the development of hamartomas
What are hamartomas?
Benign neoplastic growths of the tissue that they origin from, they cause problems based on the location of the lesion.
What do Hamartomas usually affect?
Skin Brain Lungs Heart Kidney Eyes
What is tuberous sclerosis caused by?
It is caused by mutations in one of two genes…
TSC1 gene on chromosone 9- codes for hamartin
TSC2 gene on chromosome 16- codes for tuberin
Hamartin and tuberin interact with each other to control the size and growth of cells, abnormalities in one of these proteins leads to abnormal cell size and growth.
What skin signs might you see in tuberous sclerosis.
Ash leaf spots (depigmented areas of skin which are shaped like an ash leaf)
Shagreen patches (thickened dimpled skin)
Angiofibromas
Subungual fibromata
Cafe au lait spots
Poliosis
What is a classical presentation of TS?
The classical presentation is a child presenting with epilepsy found to have skin features of tuberous sclerosis. It can also present in adulthood.
What is the management of tuberous sclerosis?
Management is supportive with monitoring and treating complications such as epilepsy. There is no treatment for the underlying gene defect.
