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Tuberous Sclerosis Complex.

Source

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

Excerpt

CLINICAL CHARACTERISTICS:

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.

DIAGNOSIS/TESTING:

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%.

MANAGEMENT:

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.

GENETIC COUNSELING:

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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