Neurocutaneous Disease Flashcards
phakomatoses
*genetic syndromes with characteristic neurologic, cutaneous, and often ocular manifestations
*examples: tuberous sclerosis, Sturge-Weber, and neurofibromatosis (NF1 and NF2)
*complete penetrance (everyone has symptoms) with variable expressivity (symptoms can be different)
two-hit hypothesis of tumor formation
requires mutation in both alleles of a tumor suppressor gene (usually first copy is mutated from inherited mutation, and then 2nd hit is usually acquired)
*haploinsufficiency = symptoms that occur when 1 copy is hit
*2nd hit is known as loss of heterozygosity (LOH)
NF1 gene - normal function
*NF1 gene codes for neurofibromin protein
*neurofibromin is responsible for shutting down cell growth by shutting down RAS phosphorylation (keeping RAS inactive to prevent tumor growth)
*when RAS is active (phosphorylated), if activates RAF, which activates MEK, which leads to cell growth and often tumors
NF-1 clinical manifestations
*skin
*eye
*bone
*brain
*nerves
NF-1 skin manifestations
*cafe au lait macules (flat, tan patches; can occur in people w/o NF-1)
*axillary and inguinal freckling
*neurofibromas
NF-1 eye manifestations
*Lisch nodules: hamartomas of the iris (brown dots on the iris)
NF-1 bone manifestations
SCOLIOSIS & SPHENOID WING DYSPLASIA
*scoliosis is the most common bony abnormality in NF-1
*sphenoid wing dysplasia is a diagnostic criteria
*other: cortical bone thinning +/- pseudoarthrosis
NF-1 brain manifestations
*brain tumors (~20% of NF1 patients); most are optic pathway gliomas!
*other lesions on MR brain:
-UBOs
-scalp neurofibromas
-stroke, moya moya
NF-1 diagnostic criteria
need 2 or more of the following:
* > 6 cafe au lait macules
*2+ cutaneous neurofibromas
*lisch nodules
*axillary/inguinal freckling
*plexiform neurofibroma
*1st degree relative with diagnosis of NF
*bony dysplasia
gene defect in neurofibromatosis 1
*NF-1 on chromosome 17
*mode of inheritance: sporadic in 50% of cases or autosomal dominant inheritance
*follows the 2-hit hypothesis
gene defect in neurofibromatosis 2
*schwannomin/merlin on chromosome 22
*sporadic in 50% of cases or AD
*follows the 2-hit hypothesis
NF-2 clinical manifestations
*vestibular schwannomas (bilateral; most common presentation of NF-2)
*intracranial meningiomas
*spinal cord ependymomas
bilateral vestibular schwannomas is indicative of?
neurofibromatosis 2 (NF-2)
NF-2 diagnostic criteria
need at least 1 of the following:
*bilateral vestibular schwannomas
*family hx of NF2 + unilateral vestibular schwannoma + two other characteristic NF2 tumors
*unilateral vestibular schwannoma + 2 other characteristic tumors
*multiple meningiomas + 2 other characteristic tumors
gene defect in tuberous sclerosis
*TSC1 (hamartin) or TSC2 (tuberin)
*defect in tumor suppressor gene
*follows the 2-hit hypothesis
