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Tuberous Sclerosis Complex.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
1999 Jul 13 [updated 2015 Sep 3].



Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, facial angiofibromas, shagreen patches, cephalic plaques, ungual fibromas); brain (cortical dysplasias, subependymal nodules and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability/developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM]). CNS tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.


The diagnosis of TSC is based on clinical findings. Heterozygous pathogenic variants can be identified in 75%-90% of individuals who meet the clinical diagnostic criteria for TSC. Among those in whom a pathogenic variant can be identified, pathogenic variants in TSC1 are found in 31% and pathogenic variants in TSC2 in 69%.


Treatment of manifestations: For enlarging SEGAs: mTOR inhibitors; neurosurgery when size causes life-threatening neurologic symptoms. For seizures: vigabatrin and other antiepileptic drugs, and on occasion, epilepsy surgery. For renal angiomyolipomas >4 cm, or >3 cm and growing rapidly: mTOR inhibitors are the recommended first line of therapy with secondary therapy options being embolization or renal sparing surgery. For LAM: mTOR inhibitors. For facial angiofibromas: topical mTOR inhibitors. For symptomatic cardiac rhabdomyomas: surgical intervention or consideration of mTOR inhibitor therapy. Prevention of secondary complications: For those on vigabatrin therapy, visual field testing at the onset of therapy, at three-month intervals for the first 18 months, and every six months afterward. Surveillance: Brain MRI every one to three years in asymptomatic individuals with TSC younger than age 25 years to monitor for new occurrence of SEGAs; those with asymptomatic SEGA in childhood should continue to be imaged periodically in adulthood; for those with large or growing SEGA or SEGA causing ventricular enlargement, more frequent brain MRIs as deemed clinically appropriate; screening for TSC-associated neuropsychiatric disorder (TAND) features at least annually at clinic visits with comprehensive formal evaluation for TAND at key developmental time points; routine electroencephalograph (EEG) in individuals with known or suspected seizure activity; MRI of the abdomen to assess for progression of angiomyolipoma and renal cystic disease every one to three years throughout the lifetime; assess renal function (glomerular filtration rate and blood pressure) at least annually; echocardiogram every one to three years in asymptomatic infants and children with cardiac rhabdomyomas until regression is documented; clinical screening for LAM symptoms (exertional dyspnea and shortness of breath) at each clinic visit in women older than age 18 years or those who report respiratory symptoms; high-resolution computed tomography (HRCT) every five to ten years in asymptomatic individuals at risk for LAM (adult females age >18 years) even when there are no signs of LAM on baseline examination; annual pulmonary function testing and HRCT every two to three years for individuals with lung cysts detected by HRCT; annual dermatologic examination; dental examination every six months; annual ophthalmology evaluation in those with previously identified ophthalmologic lesions or vision symptoms. Agents/circumstances to avoid: Smoking; estrogen use; nephrectomy Evaluation of relatives at risk: Identifying affected relatives enables monitoring for early detection of problems associated with TSC which leads to earlier treatment and better outcomes.


TSC is inherited in an autosomal dominant manner. Two thirds of affected individuals have TSC as the result of a de novo pathogenic variant. The offspring of an affected individual are at a 50% risk of inheriting the pathogenic variant. If the pathogenic variant has been identified in an affected family member, prenatal testing for pregnancies at increased risk may be available from a clinical laboratory that offers either testing for this disease/gene or custom prenatal testing.

Copyright © 1993-2016, University of Washington, Seattle. All rights reserved.

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