Neurocutaneous Flashcards
Tuberous sclerosis
ASH LEAF
Key triad
• Mental retardation
• Seizures
• Adenomas sebaceum (angiofibroma)
• A - Ashleaf spots • S- Shagreen patches • H - Heart rhabdomyosarcoma • L - Lung harmatoma • E - Epilepsy from cortical tubers • A - Angiomyolipoma • F - Facial angiofibroma
Clin Pres
Skin
• Hypomelanotic/ash leaf
• Facial angiofibromas/adeno sebaceum - acne like • Shagreen patch - rough raised on lumbar • Forehead plaque - brown fibrous • Small fibromas/nodules
Eyes
• Retinal lesions
Brain
• Cortical dyplasia
• Sub ependymal nodules
• Sub ependymal astrocytomas
• Epilepsy - infantile spasms, hypsarrythmias
• Cognitive impairment/ID
• Behaviour
Renal
• Renal angiomyolipoma
• Single/multiple cysts
• Renal cell carcinoma
Other
• Cardiac rhabdomyosarcoma
• Pulmonary lesion - lymphangioleiomyomatosis
Surveillance
• Brain - MRI, EEG
• Renal - imaging
• Cardiac - Echo, ECG
• Resp
Mx
• mTOR inhibitors - sirolimus, everolimus
• Renal - embolisation
Seizures - vibabactrin
Neurofibromatosis Type 1
Cause
• Loss of function of NF1 gene which is tumour suppressor gene encoding neurofibromin
Clinical Manifestations
Skin
• Café au lait macules - 100%, common to have 1-2 in general population
• Axillary or inguinal freckles - skin fold, >80% by 6
Eyes
• Iris Lisch nodules - hamartomas on iris - slit lamp, >75%
Tumours
• Peripheral neurofibromas - peripheral nerve sheath tumours compromised Schwann cells
• Neurofibroma - focal growth - no risk malignant transformation
• Plexiform neurofibroma - extent longitudinally along nerve, can become malignant
• Optic pathway gliomas - intracranial neoplasm, 15%
• Other CNS tumours
• Soft tissue sarcomas - malignant peripheral sheath tumours - pain
Bone
• Scoliosis - 10-25%
• Long bone dysplasia, pseudoarthrosis
• Sphenoid wing dysplasia
Neurological
• Cognitive deficits/ID - 50%
• ASD
• Seizures - 5%
• Periph neuropathy
Other
• UBOs - hyperintense regions on T2 MRI
• Macrocephaly
• Pubertal disturbance
• Hypertension- 6% - usually essential but vascular lesions causing secondary are common in NF1 - renal artery stenosis, phae
• Short stature
• Hypothalamus
• Sensorineural deafness - infrequent, occurs in 5%
Mx
• Yearly review - surveillance
• Neuro, BP, scoliosis, opthal, MRI for lesions, learning evaluation
• Manifestations - surgical
• Pham - carboplatin for optic glioma
NF2
• Loss of function of NF2 (tumour suppressor gene)
• Hearing loss, tinnitus, focal weakness
Clin manifestations
Vestibular schwannomas - can be bilateral
• Tinnitus, hearing loss, balance
• Everyone by age 30
Other CNS tumours
• Meningioma (80%)
• Schwannoma - other locations
• Glioma
• Neurofibroma
Eye
• Posterior subcapsular lenticluar opacities
• Retinal harmatomas
Other
• Neuropathy
Mx
• Surveillance - annual MRI, hearing, opthal
Manifestations - surgical, hearing loss, bevacizumab (shrinks schwannomas)
Sturge-Weber
• Sporadic vascular disorder
• Port wine stain (facial capillary malformation)
• Abnormal blood vessels brain
• Abnormal blood vessels eye - glaucoma
• Seizures/epilepsy 75-90%
• Stroke like episodes/hemiparesis
• Headache
Dev delay
Von Hippel-Landau
• Cystic lesions of kidney, pancreas, liver - renal cell carcinoma most common cause death
• Neuro - haemangioblastomas - cerebellar, spinal
Retinal angiomas
PHACE syndrome
• P - posterior fossa malformation
• H- haemangiomas of face
• A- arterial anomalies
• C - cardiac anomalies
E - eye abnormalities
Tuberous Sclerosis - genetics
• Autosomal dominant (2/3 new, 1/3 FHx)
• Abnormal TSC1 or TSC2 (tumour suppressor gene) –> encode tuberin and hamartin –> abnormal signalling/expression –> hamartomas
• Multiple benign harmartomas (benign growth disorganised cells) of multiple organs
• Tuber = potato
TS - skin findings and approx %
SKIN
3 Hypomelanotic depigmented lesions (Ash leaf)
· May only be seen on Woods lamp
· Present in nearly all
Shagreen patch
· Leathery
· 60%
Ungual/periungal fibroma
· Nail
Facial Angioma or Forehead plaque
· Adenoma sebaceum “acne like” - 75%
· Butterfly/malar region
· Forehead plaque - distinctive brown fibrous plaque on forehead - 25%
TS - brain and CNS findins
BRAIN (>75%)
· Cortical tubers “potatoes”
· Subependymal nodules
· Astrocytoma - subependymal giant cell astrocytoma
· Can cause hydrocephalus
· White matter radial migration
· Seizures
· ID
Behavioural issues
TS - renal, cardiac, other and complications?
RENAL (common 80%)
· Renal angiomyolipomas
· Can bleed
· Multiple renal cysts - benign
· Renal cell carcinoma 3%
CARDIAC
· Cardiac angiomyolipomas
· Rhabdomyomas
OTHER
Opthal
· Retinal lesions (harmatomas), Mulberry lesions
RESP
· LAM - lymphangiomyomatosis
Complications
· 85% with TS have Cx
· Seizures - infantile spasms - 20% will have TS, myoclonic, partial, GTCS, can be refractory to Tx
· Intellectual Disability 50% - mild to severe
Behaviour - ADHD, autisim, sleep
TS - surveillance, Mx and counselling?
Surveillance
• Brain - MRI, EEG
• Renal - imaging
• Cardiac - Echo, ECG
• Resp
Mx
• mTOR inhibitors - sirolimus, everolimus
• Renal - embolisation
• Seizures - vigabactrin
Genetic counselling
• Must assess parents - Woods lamp, MRI brain, renal, opthal
If normal, recurrent risk 2% (not 0% gonadal mosaicism)
