Neurofibromatosis Flashcards
Neurofibromatosis is autosomal dominant neurocutaneous syndrome with multi-organ involvement affecting skin, soft tissue, nervous system and bones.
Neurofibromatosis type 1
Chromosome 17 encodes neurofibromin (tumour suppressor), acts as negative regulator of Ras-oncoprotein protein kinase signaling pathway
NF1 incidence of 1 in 3000, variable penetrance
1/2 cases familial, remainder de-novo mutation
Neurofibromatosis type 2
Chromosome 22 encodes cytoskeletal protein (merlin) that function as tumour suppressor.
NF2 is less common than NF1, incidence 1 in 25000, full penetrance
1/2 cases familial, remainder de-novo mutation
Schwannomatosis
Proposed new subtype of NF
Incidence of 1 in 30,000
What are the clinical features of NF1?
Neurocutaneous
1. Cafe au lait macules
2. Axillary or inguinal freckling
3. Cutaneous neurofibromas along peripheral nerves
Eye
4. Optic glioma - proptosis, reduced visual acuity
5. Lisch nodules
6. Pulsatile exopthalmos
Musculoskeletal
7. Sphenoid wing dysplasia
8. Long bone lesion - tibial abnormality
9. Pseudoarthrosis, bowing and fractures
10. Scoliosis
11. Short stature
Neurology
12. Seizures
13. Headaches and migraines
14. Learning disability
15. Autism spectrum disorder
Cardiorespiratory
16. Heart abnormalities - pulmonary stenosis, HOCM
17. Pulmonary fibrosis
What are the associated conditions of NF1?
- Breast cancer
- Phaeochromocytomaa - hypertension, headache
- Wilms tumour - haematuria, hypertension, abdominal mass
- Leukaemia
- Myelodysplastic syndrome
Describe the lesion and its association
Criteria of lesion to ascertain diagnosis
Cafe au lait macules
Associated with neurofibromatosis type 1 (less in NF2)
Shape: irregular, but well-dermacated, smooth border; (or oval shaped, size 1-4cm)
Colour: homogenous hyperpigmented dark brown colour
Quantity: multiples (at least 6)
Onset: occurs by age 2
Describe the lesion and its association
Commonly affected location and size
Skinfold freckling (Crowe sign)
Neurofibromatosis type 1
Shape: freckles, size 1-3mm
Location: areas with minimal sun exposure
Commonly over axilla, inguinal, neck, breasts, lips, trunks
Onset: occurs by age 3-5
Describe the lesion and its association
Cutaneous and subcutaneous neurofibroma
Neurofibromatosis type 1
Cutaneous neurofibromas
Soft, fleshy consistency
Painful
Multiple shapes and sizes: flat, dome, sessile, pedunculated
Cutaneous: chest, abdomen, back, limbs
Subcutaneous neurofibromas
Firm, rubbery, bead/pea like nodules
Subcutaneous: along nerves under epidermis
Painful and tender
Associated with nerve root compression - causing radicular pain, weakness, sensation loss
Describe the lesion and its association
Plexiform neurofibromas
Neurofibromatosis type 1
Thickened skin, hyperpigmented with hypertrichosis
“Bag of worm” sagging appearance
Painful and tender
Occurs oer the neck, neck, abdomen, limb
May develop into malignant schwannoma
Describe the lesion and its association
Lisch nodules
Neurofibromatosis type 1
Multiple small, dome-shaped, hyperpigmentation on the iris
Describe the lesion and its association
Sphenoid wing dysplasia
Neurofibromatosis type 1
Hypoplastic or absent sphenoid wing causing widerning of superior orbital fissure, elevation of lesser spehnoid wing and ipsilateral orbital enlargement
Gaping bony defect in posterior aspect of orbit
Pulsatile exopthalmos
What are the differences between NF1 vs NF2?
NIH Diagnostic Criteria for NF1
At least 2 of the following:
1. At least 2 neurofibromas
2. At least 6 cafe au lait spots
3. Axillary or inguinal freckling
4. Optic glioma
5. At least 2 Lisch nodules
6. Distinctive osseous lesions or dysplasia
7. First degree relative with NF1
Neurofibromatosis “dance”
(Physical examination sequence)
General inspection
1. Growth - stunted growth, short stature
2. Head size- macrocephaly
3. Skin - front, back, UL and LL for café au lait and neurofibromas
4. Musculoskeletal - sphenoid wing dysplasia, kyphoscoliosis,
5. Developmental assessment (in children)
Facial examination
6. Cranial nerves - CN5, CN7, CN8, CN9 (CP angle tumour)
- Tuning Fork Test for SNHL
7. Look for hearing aid
8. Eyes - fundoscopy for optic glioma, Lisch nodule, hamartoma, vision loss
Cardiorespiratory
9. Pulmonary stenosis, HOCM, restrictive CM
10. Pulmonary fibrosis
11. Signs of hypertension (RAS bruit, phaeochromocytoma)
Lower limbs
12. Musculoskeletal: Charcot joint, tibial bowing
Baser Score for NF2
Neurofibromata biopsy and histology reveals tumour composed of Schwann cells, fibroblasts, mast cells and vascular components
