90B - Neurofibromatosis Flashcards
Neurofibromatosis is __ disorder affecting skin, soft tissue, nervous system and bones.
NF1 incidence of __, __ penetrance
1/2 cases are __, remainder are __
NF1 gene is located on __, encodes __ (GTPase) that activates protein GAP, which acts as negative regulator of RAS-mitogen-activated protein kinase signaling pathway
NF2 is less common than NF1, incidence __, __ penetrance
1/2 are __, remainder __
NF2 gene on __, encoding cytoskeletal protein, merlin that function as tumour suppressor.
Schwannomatosis is a new subtype of NF
Incidence of __
Autosomal dominant
NF1
1 in 3000, variable penetrance
1/2 familial, remainder de-novo mutation
Chromosome 17, neurofibromin (tumour suppressor)
NF2
1 in 25,000, full penetrance
1/2 familial, remainder de-novo mutation
Chromosome 22
Schwannomatosis
1 in 30,000
What are the clinical features of NF1?
- Cafe au lait macules
- Axillary or inguinal freckling
- Cutaneous neurofibromas
- Optic glioma - proptosis, reduced visual acuity
- Lisch nodules
- Sphenoid wing dysplasia
- Pulsatile exopthalmos
- Long bone lesion - tibial abnormality
- Pseudoarthrosis, bowing and fractures
- Scoliosis
- Short stature
- Seizures
- Headaches and migraines
- Heart abnormalities - pulmonary stenosis, HOCM
- Pulmonary fibrosis
- Learning disability
- Autism spectrum disorder
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)
Well-dermacated, smooth border
Homogenously hyperpigmented dark brown coloured
Oval shaped, size 1-4cm
Multiples (at least 6)
Occurs by age 2
Describe the lesion and its association
Commonly affected location and size
Skinfold freckling (Crowe sign)
Neurofibromatosis type 1
Freckles, size 1-3mm
Occurs in areas with minimal sun exposure
Commonly over axilla, inguinal, neck, breasts, lips, trunks
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” - must be irregardless of type
(Physical examination sequence)
- General examination for HTN, stunted growth, macrocepehaly
- Skin examination of front, back, UL and LL for café au lait and neurofibromas
- Ear examination for hearing loss by Tuning Fork Test
- Eye examination for Lisch nodule, vision loss
- CN examination – especially CN5, 7, 8, 9
- Cardiovascular and respiratory – pulmonary stenosis, HOCM, pulmonary fibrosis
- Developmental assessment (in children)
Baser Score for NF2
