neurocutaneous syndromes Flashcards
NF1 vs 2 genetics
NF1 = AD loss of NF1 tumour suppressor encoding neurofibromin; 30% de novo
NF2 = AD loss of NF2 tumour suppressor encoding merlin, 50% de novo
diagnostic criteria for NF1
2 or more of the 7:
1. Six or more café-au-lait macules = >5mm pre-pubertal, >15mm post-pubertal
2. Axillary or inguinal freckling = multiple hyperpigmented 2-3mm
3. Two or more iris Lisch nodules = hamartomas located in the iris
4. Two or more neurofibromas or 1 plexiform neurofibroma
5. Distinctive osseous lesion
6. Optic gliomas
7. 1st degree relative with NF-1
examples of distinctive osseous lesions in NF1
- sphenoid dysplasia: may cause pulsating exophthalmos/facial asymmetry
- long bone dysplasia +/- pseudoarthrosis esp. tibia
- scoliosis
distinguishing features between NF1 and NF2
NF2:
rare CAL spots
uncommon axillary / inguinal freckling
no iris lisch nodules
DO have posterior subcapsular lenticular opacities
cause schwannomas not NF
rare malignant transformation
MRI annual from 10y - but NF1 not recommended!
types of fibromas present in NF1, and which is the worst
- regular nodular neurofibroma (peripheral nerve sheath tumour)
- Plexiform neurofibroma extend along a nerve > 10% malignant transformation into a neurofibrosarcoma
types of cancers NF1 patients are at risk of
- optic glioma in 15% <6y - usually low-grade pilocytic astrocytoma
- other CNS tumours 5x more common
- soft tissue sarcoma
- MPNST as older adult
- rhabdomyosarcoma
- Wilm’s, phaeochromocytoma
- JMML
what behavioural/mental / neuro things can NF1 people get
behavioural: ASD
mental: ID
neuro: seizures, peripheral neuropathy, macrocephaly
reasons for HTN in NF1
- most still essential HTN
- RAS 1.5%
- phaeochromocytoma 0.7%
when do the cutaneous symptoms of NF1 pop up based on age?
cafe-au-lait from birth to 2y
axillary freckling to 6y
plexiform neurofibromas 6-10y
classic feature of NF1 on MRI
UBO’s = hyperintense regions on T2 MRI esp. cerebellum
Rx of optic glioma in NF1
Carboblatin for optic glioma
2 major DDx of NF1
- legius syndrome: freckling/CAL spots but no neurofibromas, optic nerve gliomas, bone lesions
- LEOPARD syndrome = Noonan syndrome with multiple lentigines
features of LEOPARD syndrome
- Lentigines – flat, black-brown macules
- ECG - Hypertrophic cardiomyopathy
- ocular hypertelorism
- Pulmonary stenosis
- abnormal genitals
- retarded growth
- deafness
key features of NF2
- Vestibular schwannomas (uni>bilat) > hearing loss, imbalance, tinnitus
- other cancers: meningioma, other schwannoma esp spinal, and other CNS
- Posterior subcapsular lenticular opacities»_space; cataracts
- retinal hamartoma»_space; haemorrhage
- Mono or polyneuropathy
Rx for vestibular schwannoma
avastin (bevacizumab)
classic triad of tuberous sclerosis
- mental retardation
- seizures
- angiofibromas
mnemonic for TS features
ASH LEAF:
ashleaf spots
shagreen patches
heart rhabdomyosarcoma
lung hamartoma
epilepsy
angiomyolipoma
facia angiofibroma
genetics of tuberous sclerosis
TSC1 encodes hamartin protein, less common
TSC2 encodes tuberin protein, more common
1/3 genetic, 2/3 de novo
both tumour suppressors
major diagnostic criteria for TS
Definite = 2 major OR 1 major + 2 minor
Probable = 1 major + 1 minor
Possible TS = 1 major or 2 minor
Cutaneous
• Hypomelanotic macules (>=3, >=5mm in diameter)
• Angiofibromas [= adenoma sebaceum] (>=3) or fibrous cephalic plaque [= forehead plaque]
• Ungal fibromas (>=2)
• Shagreen patch
Brain
• Cortical dysplasia – including tubers and cerebral white matter migration lines
• Subpendymal giant cell astrocytoma (SEGA)
• Subependymal nodules (SENs)
Other
• Eyes = multiple retinal nodular hamartomas
• Heart = Cardiac rhabdomyoma (>=1)
• Lymphangioleiomyomatosis (LAM)
• Renal Angiomyolipoma (>=2)
what is important to remember of lymphangioleiomyomatosis presentation?
classic pulmonary lesion only affects women >20y
what are they, and why do we care about SENs and SEGAs
Sub ependymal nodules (SEN) along lateral ventricular walls > 10% become sub-ependymal giant cell astrocytomas (SEGAs) > block CSF circulation
what kind of surveillance would TS patients need
- MRI = every 1-3 years at least; at least 1 EEG
- Renal: imaging and BP/renal function
- echo 1-3y, ECG 3-5y
- HRCT 5-10y for LAM
HRCT every 5-10 years - annual derm, dent, ophthal
Rx for tuberous sclerosis
- mTOR inhibitor sirolimus for skin, LAM, AMLipoma, SEGA, cardiac rhabdomyoma
- renal AMLipoma - embolisation + roids
- seizures - vigabatrin
key features of sturge-weber syndrome
- port wine stain at 1st/2nd div of trigeminal
- ipsi leptomeningial angioma > contralat seizures or stroke-like episodes with hemiparesis or headache
- glaucoma
4.tram track calcifications on MRI - somatic!
- dev delay in 50%
key features of von hippel-laundau
mostly inherited, AD of tumour suppressor gene causing tumours in CNS, kidneys, liver and pancreas:
- haemangioblastomas: spine/brain/retina»_space; cerebellar issues, hydrocephalus, blindness
- Cysts of kidneys, pancreas, liver, adrenals, ear»_space; phaeo or worser metastatable ones - RCC, panc tumour
most common cause of death in VHL
RCC
key features of PHACE syndrome
PHACE(S):
Posterior fossa malformation esp. dandy-walker
Haemangiomas of the face, ipsi to aortic arch
Arterial anomalies, carotids weird
Cardiac: coarct
Eyes: glaucoma, cataracts, microphthalmia
ventral developmental defects: Sternal clefting, supraumbilical raphe
key features of Incontinentia Pigmenti
X-linked dominant - lethal in males, with skin lesions of 4 stages:
evolve through four stages
1. Blistering = birth to 4 months
1. Can be confused for herpes
ii. Wart like rash = for several months
iii. Swirling macular hyperpigmentation (age 6 months to adulthood)
iv. Linear hypopigmentation (hairless)
