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tuberous sclerosis* - Coggle Diagram
tuberous sclerosis*
management
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nephrology
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blood pression, proteinuria, GFR at least annually
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risk of maligancies: kidneys, brain, soft tissues
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neurology
brain MRI with and without gadolinium: onset, every 1-3 y up to 25y
EEG: at presentation, sezure, behavioral and neurological changes; vigabatrin for infantile spasms and for focal seizures <1 year;focal seizures: oxcarbazepin, levetiracetam, zonisamide
TAND checklist: 0, 3, 6, 9, 12, 16 y
pathogenesis
pathogenic variants (loss of function) cause overactivation of the mechanistic target of rapamycin (mTOR) pathway
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mTOR pathway: regulates cell growth and proliferation via protein translation, cell cycle progression, response to hyoxia
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Increased mTOR activity during development may also impact the developing neural network, alter synaptic transmission, and shift the excitation/inhibition balance in favor of excitation; these changes could promote development of epilepsy and TSC-associated neuropsychiatric disorders (TAND)
clinical features
variable phenotype, progressive
presentation
infancy: seizures, hypomelanotic macules, cardiac rhabdomyoma
childhood: seizures, hypomelatonic macules, forehead plaque, angiofibromas - teens, complications of subependymal giant cell astrocytomas
adulthood: renal angiomyolipma, periungual fibroma, lymphangioleiomyomatosis
brain lesions
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subependymal nodules -> subependymal giant cell astrocytoma (SEGAs) = subependymal giant cell tumors (SGCTs) (histologically undistinguishable
white matter lesions: nodules, cysts, areas of gliosis, hypomyelination; linear lesions from ventricle to cortex with SEN or subcortical lesion on each end
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seizures and epilepsy
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types: infantile spasms 36-69% (25% of infantile spasms), focaé, focal to bilteral tonic-clonic, subclinical, generalized (less common)
EEG: 75% abnormal, focal, multifocal, hypsarrythmia, generalized spike and wave
risk factors: cortical tubers with central low FlAIR signal, TSC2
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systemic
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opthalmologic: retinal hamartoma, chorioretinal depigmentation, exelid angiofibroma, nonparalytic strabismus, coloboma, iris depigmentation
oral and dental: intraoral fibroma, gingival hyperplasia, dental enamel pits, deforming jaw cysts
cardiovascular: cardiac rhabdomyoma - in utero, coarctation of the aporta, constriction of major arterias - renal artery stenosis
renal: angiomyolipma, bening cysts, lymphangioa, renal cell carcinoma, renin-dependent hypertension
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evaluation
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physical: skin, neurology for hydrocephalus, paplledema, focal deficitis, ophtalmology
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genetic testing: 10-15% no pathogenic variant on standard testing! - somatic mosaicism 2-10%, splice-region variants
first-degree relatives: genetic, sking, opthalmologic, MRI: cranial, abdominal
ref
UpToDate: Tuberous sclerosis complex: Genetics and pathogenesis, Literature review current through: Jul 2024.
UpToDate: Tuberous sclerosis complex: Clinical features, Literature review current through: Jul 2024.
UpToDate: Tuberous sclerosis complex: Evaluation and diagnosis, Literature review current through: Jul 2024.
UpToDate: Tuberous sclerosis complex: Management and prognosis, Literature review current through: Jul 2024.
genetics
autosomal dominant, complete penetrance, highly variable expressivity
tumor supressor genes
TSC1 ->hamartin; 1/3, 9q34
TSC2 ->tuberin; 2/3, 16p13.3, more severe neurological phenotype and higher risk of renal malignancy
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diagnosis
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clinical criteria
major features
Hypomelanotic macules (≥3, at least 5 mm diameter)
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diagnostic certainty
definite: 2 major OR 1 major + 2 minor, except LAM and angiomyolipomas
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def: neurocutaneous disorder, benign hamartomas in brain, eye, heart, lung, kidney, skin
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