Neurofribromatosis Flashcards
What is the epidemiology of neurofibromatosis type 1 (NF1)?
1/3500 (USA)
M/F equally affected
What is the aetiology and pathophysiology of NF1?
Genetic condition – NF1 gene dysfunction – protein is a tumour suppressor - dysfunction leads to benign tumours of peripheral nerves
How does NF1 progress?
Progressive presentation over years; lots of individual variation but normal life expectancy
How does NF1 present?
Café au lait spots – pale coffee coloured patches; present at birth or developing by age 3, usually at least 6x5mm, growing to 15mm in adulthood
Neurofibromas – soft, non-cancerous tumours of nerves, on or under skin, sometimes purple, not usually painful; plexiform neurofibromas = neurofibromas in places where multiple branches of nerves come together – can cause large swellings that can be painful or cause neurological/GI/micturition changes or bleeding
Clusters of freckles – axillary, groin and under breast (but anywhere)
Eye – 15% will develop tumours of the optic pathway (optic pathway gliomas); most common in children under 7; usually asymptomatic and slow growing; sometimes – blurring, colour vision, visual fields are affected; Lisch nodules = tiny raised brown spots in iris
Sometimes learning and behaviour is affected – lower IQ; ADHD in 50% of children; links to ASD
HTN – secondary to renal artery stenosis – requires treatment
Development – scoliosis (10%), larger head (50%), smaller size and lower weight
CNS – migraines are common; brain tumours and epilepsy are rare but possible
Cancer – malignant peripheral nerve sheath tumour (MPNST) – following plexiform neurofibromas – 15% lifetime probability, 20s-30s most common incidence; gastrointestinal cancer also possible
How do you manage NF1?
Referral to specialist units at Guys London and Central Manchester
Monitoring – at least once yearly as a child then less frequently when they learn to self-monitor:
Skin examination – for plexiform neurofibromas
BP
Vision test and examination of both eyes – slit lamp examination
Bone assessments including vitamin D levels – scoliosis and poorly healed fractures
Behavioural and neurological assessments
Physical development
Progress in school
Emotional wellbeing/employment
Skin problems: Café au lait – make-up, psychotherapy;
Neurofibromas – plastic surgery if pain or distressing
Learning difficulties + behavioural problems, Specialist support:
i) SALT
ii) OT
iii) Educational psychologists
iv) Psychiatrists
BP: Salt intake watching; Exercise; Weight management; Reduction of alcohol and smoking; Maybe medication
Malignant tumours: Resection, radio and chemotherapy if appropriate
Epilepsy: Normal management
What is the epidemiology of NF type 2?
1/25000 (USA)
M/F equally affected
What is the aetiology and pathophysiology of NF2?
Genetic
i) Faulty NF2 gene
ii) Autosomal dominant in half of individuals
iii) Spontaneous development in the other - these children can pass on these genes though parent is unlikely to have another child with it
Benign tumours of Schwaan cells – specifically for nerves used for hearing and balance
i) Vestibular schwannomas
What is mosaic NF2?
Mosaic NF2:
i) 1/3 with NF2 have a milder form that is restricted to 1 area or side of the body
ii) Lower than the usual 50% transmission rate
How does NF2 progress?
Start in the late teens early 20s; progressive with higher mortality risk
How does NF2 present?
Hearing loss that worsens over time
Tinnitus
Balance problems – especially in the dark or walking on uneven ground
Possible vertigo, N+V
As tumours grow – facial numbness, weakness of tongue (dysarthria/dysphagia)
Cataracts – 2/3rds, usually mild
Some similar symptoms to NF1 ie skin schwannomas, café au lait spots (usually fewer)
Peripheral neuropathy – sensation changes distally (tingling, pain, numbness), weakness
CNS – ½ of people - meningiomas (benign); usually asymptomatic but can cause mass effect problems or focal deficits depending on size and location
Spinal cord – ½ people – ependymomas (spinal cord tumours), back pain, muscle weakness, sensation changes in legs/arms
How is NF2 managed?
Referral to specialist centres
Monitoring (possibly more frequent depending on symptoms):
Annual MRI – full body – for tumour location and change mapping
Annual eye tests – cataracts
Annual hearing tests – hearing loss
Tumours:
Surgery, radiotherapy = difficult decisions due to locations and risk:benefit analysis must be undertaken
Ears:
Hearing aids/Cochlear implants/Auditory brainstem implants/Lip reading
Treat any other complications/symptoms as they arise
Genetic counselling for parents and any affected children when appropriate
