Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management

Publication Date: July 23, 2021
Last Updated: March 14, 2022
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Surveillance and Management Recommendations for Newly Diagnosed or Suspected TSC
Organ System or Specialty Area Recommendations
Genetics Obtain three-generation family history to assess for additional family members at risk of TSC.
Offer genetic testing for family counseling or when TSC diagnosis is in question but cannot be clinically confirmed.
Brain Obtain MRI of the brain to assess for the presence of tubers, SEN, migrational defects, and SEGA.
During infancy, educate parents to recognize infantile spasms and focal seizures, even if none have occurred at the time of first diagnosis.
Obtain baseline routine EEG while awake and asleep. If abnormal, especially if features of TAND are also present, follow-up with 8- to 24-h video-EEG to assess for seizure activity.
TAND Perform comprehensive assessment for all levels of potential TAND manifestations (see Fig of TAND umbrella for details of levels). Refer as appropriate to suitable professionals to initiate evidence-based interventions based on the TAND profile of above-identified needs.
Provide parent/caregiver education and training about TAND to ensure families know what to look out for in emerging TAND manifestations (e.g. autism spectrum disorder, language disorders, attention-deficit/hyperactivity disorder, anxiety disorders). Provide psychological and social support to families around diagnosis, coming to terms with the diagnosis of TSC and TAND, and ensure strategies are in place to support caregiver well-being.
Kidney Obtain MRI of the abdomen to assess for the presence of angiomyolipomas and renal cysts.
Screen for hypertension by obtaining an accurate blood pressure. Evaluate renal function by determination of GFR.
Lung Inquire about tobacco exposure, connective tissue disease manifestations, signs of chyle leak, and pulmonary manifestations of dyspnea, cough, and spontaneous pneumothorax in all adult patients with TSC.
Perform baseline chest CT in all females, and symptomatic males, starting at age 18 years or older.
Perform baseline PFTs and 6MWT in patients with evidence of cystic lung disease consistent with LAM on the screening chest CT.
Skin Perform a detailed clinical dermatologic inspection/examination.
Teeth Perform a detailed clinical dental inspection/examination.
Heart Consider fetal echocardiography to detect individuals with high risk of heart failure after delivery when rhabdomyomas are identified via prenatal ultrasound.
Obtain an echocardiography in pediatric patients, especially if younger than age three years.
Obtain an electrocardiography at all ages to assess for underlying conduction defects.
Eye Perform a complete ophthalmologic evaluation, including dilated fundoscopy, to assess for retinal findings (astrocytic hamartoma and achromic patch) and visual field deficits.
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Surveillance and Management Recommendations for Patients Already Diagnosed With Definite or Possible TSC
Organ System or Specialty Area Recommendations
Genetics Offer genetic testing and family counseling if not done previously.
Brain Obtain MRI of the brain every 1-3 yr in asymptomatic patients with TSC younger than age 25 yr to monitor for new occurrence of SEGA. Patients with large or growing SEGA, or with SEGA causing ventricular enlargement who are asymptomatic, should undergo MRI scans more frequently, and the patients and their families should be educated regarding the potential of new symptoms. Patients with asymptomatic SEGA in childhood should continue to be imaged periodically as adults to ensure there is no growth.
Surgical resection should be performed for acutely symptomatic SEGA. Cerebrospinal fluid diversion (shunt) may also be necessary. Either surgical resection or medical treatment with mTORi may be used for growing but otherwise asymptomatic SEGA. For large tumors, if clinical condition enables, neoadjuvant treatment with mTORi may facilitate surgery. Minimally invasive surgical techniques may increase surgical safety in selected patients. In determining the best treatment option, discussion of the complication risks, adverse effects, cost, length of treatment, and potential impact on TSC-associated comorbidities should be included in the decision-making process.
Obtain routine EEG in asymptomatic infants with TSC every 6 weeks up to age 12 months and every 3 months up to age 24 months, as abnormal EEG frequently precedes onset of clinical seizures.
Obtain routine EEG in individuals with known or suspected seizure activity. The frequency of routine EEG should be determined by clinical need rather than a specific defined interval. Prolonged video-EEG, 24 hr or longer, is appropriate when seizure occurrence is unclear or when unexplained sleep, behavioral changes, or other alteration in cognitive or neurological function is present.
Vigabatrin is the recommended first-line therapy for infantile spasms. ACTH, synthetic ACTH, or prednisolone can be used if treatment with full-dose vigabatrin for 2 weeks has not correlated with clinical and EEG improvement.
Other than infantile spasms, antiseizure medications for other seizure types in TSC should generally follow that of other epilepsies. Everolimus and a specific cannabidiol formulation are approved by regulatory authorities for treatment of seizures associated with TSC. No comparative effectiveness data exist to recommend antiseizure medications, everolimus, cannabidiol, or dietary therapies over one another in specific subsets of patients.
Epilepsy surgery should be considered for TSC patients with refractory seizures, seizures, particularly after failing three medications. Special consideration should be given to children at younger ages experiencing neurological regression, and evaluation for surgery should be performed at centers with experience and expertise in TSC.
TAND Perform annual screening for TAND, using validated screening tools such as the TAND Checklist ( checklists/). Screening may be done more frequently depending on clinical needs. When any concerns are identified on screening, proceed to further evaluations by appropriate professionals to diagnose and treat the relevant TAND manifestations. Perform comprehensive formal evaluation for TAND across all levels of TAND (see Fig of TAND umbrella) at key developmental time points: infancy (0-3 yr), preschool (3-6 yr), premiddle school (6-9 yr), adolescence (12-16 yr), early adulthood (18-25 yr), and as needed thereafter.
Refer to appropriate professionals for the management/intervention of relevant TAND manifestations. Interventions should be personalized to the TAND profile of each individual and be based on evidence-based practice guidelines/practice parameters for individual manifestations (e.g., autism spectrum disorder, attention-deficit/hyperactivity disorder, anxiety disorder).
Aim for early identification of TAND manifestations and early intervention.
Many people with TSC have academic/scholastic difficulties. Therefore, always consider the need for an individual educational program.
Sudden and unexpected change in behavior should prompt physical evaluation to look at potential medical causes (e.g., SEGA, seizures, renal disease, medications).
Provide psychological and social support to families and caregivers and ensure strategies are in place to support caregiver well- being. Continue to provide parent/caregiver education and training about TAND to ensure families know what to look out for in emerging TAND manifestations across the lifespan.
Kidney Obtain MRI of the abdomen to assess for the progression of angiomyolipoma and renal cystic disease every 1-3 years throughout the lifetime of the patient.
Assess renal function including determination of glomerular filtration rate, proteinuria, and blood pressure at least annually. Embolization followed by corticosteroids is the first-line therapy for angiomyolipoma presenting with acute hemorrhage.
Nephrectomy is to be avoided. For asymptomatic, growing angiomyolipoma measuring larger than 3 cm in diameter, treatment with an mTORi is the recommended first-line therapy. Selective embolization or kidney-sparing resection are acceptable second-line treatments for asymptomatic angiomyolipoma.
Lung Inquire about smoking, occupational exposures, connective tissue disease symptoms, chyle leak, and pulmonary manifestations, such as dyspnea, cough, and spontaneous pneumothorax in all adult patients at each clinic visit.
For adult females with a negative screening chest CT who remain asymptomatic, repeat to screen for the presence of LAM every 5-7 years through menopause.
For patients with evidence of cystic lung disease consistent with LAM on screening chest CT, follow-up scan intervals should be determined on a case-by-case basis depending upon the individual circumstances, such as the presence or absence of symptoms, the ability to perform reliable PFTs, pre-existing use of mTORis for other TSC indications, treatment response (or the lack thereof), or development of other pulmonary complications.
Perform routine serial pulmonary function test monitoring at least annually in patients with evidence of LAM on chest CT, and more frequently in patients who are progressing rapidly or who are being monitored for response to therapy.
Use mTORi for treatment of LAM in patients with abnormal lung function (FEV1 < 70% predicted), physiological evidence of substantial disease burden (abnormal DLCO [<80% or less than lower limit of normal (when available)]), air trapping
(RV > 120%), resting or exercise-induced oxygen desaturation, rapid decline (rate of decline in FEV1 > 90 mL/year), and problematic chylous effusions.
Counsel patients regarding the risk of pregnancy and exogenous estrogen use. Avoid routine use of hormonal therapy or doxycycline for the treatment of LAM. Advise patients against tobacco smoke exposure including the use of electronic cigarettes and vaping.
Trial inhaled bronchodilators in patients with symptoms of wheezing, dyspnea, chest tightness, or obstructive defect on spirometry, with continued use in patients who derive symptomatic benefit
Consider measurement of annual VEGF-D levels in patients who are unable to perform reliable pulmonary function tests to monitor adequacy of pharmacodynamic suppression of the mTOR pathway.
Encourage age-appropriate vaccinations, such as annual influenza vaccination, inactivated recombinant shingles vaccination, and both 13-valent and 23-valent pneumococcal vaccinations. Patients on mTOR inhibitors should receive the recombinant varicella vaccine regardless of age and avoid all live vaccines.
Educate patients and families about the signs and symptoms of a pneumothorax and advise them to seek medical attention if they experience any of these symptoms. Offer pleurodesis following the first episode of pneumothorax rather than waiting for a recurrent event. Counsel patients that pleurodesis does not preclude future lung transplantation.
Skin Perform annual skin examinations for children with TSC. Adult dermatologic evaluation frequency depends on the cutaneous manifestation. Close surveillance and intervention are generally recommended for TSC-related skin lesions that rapidly change in size and/or number; cause functional interference, pain, or bleeding; or inhibit social interactions.
Provide ongoing education on sun protection.
For flat or minimally elevated lesions, topical mTORi treatment is recommended. Watch for improvement in skin lesions over several months; if lesions do not improve, or if earlier intervention is indicated, then consider use of surgical approaches. For protuberant lesions, consider surgical approaches (e.g. excision, lasers).
Teeth Perform a detailed clinical dental inspection/examination at minimum every 6 months. Take a panoramic radiograph to evaluate dental development or if asymmetry, asymptomatic swelling, or delayed/abnormal tooth eruption occurs. Enamel pits may be managed by preventive measures as first-line treatment (sealants, fluoride). These pits may be managed by restorations if preventive measures fail, or if symptomatic, carious, or there is an aesthetic concern. Symptomatic or deforming oral fibromas and bony jaw lesions should be treated with surgical excision or curettage when present.
Heart Obtain an echocardiography every 1-3 years in asymptomatic pediatric patients until regression of cardiac rhabdomyomas is documented. More frequent or advanced diagnostic assessment may be required for symptomatic patients.
Obtain electrocardiography every 3 to 5 years in asymptomatic patients of all ages to monitor for conduction defects. More frequent or advanced diagnostic assessment such as ambulatory and event monitoring may be required for symptomatic patients.
Eye Perform annual ophthalmic evaluation for those with or without visual symptoms at baseline. Rare cases of aggressive lesions or those causing vision loss due to their location affecting the fovea or optic nerve may require intervention. mTOR inhibitors have been used with some success to treat problematic retinal astrocytic hamartomas.
For patients receiving vigabatrin, there are specific concerns related to visual field loss, which appears to correlate with total cumulative dose. Physicians responsible for monitoring children on vigabatrin can offer serial fundoscopic examinations to detect retinal changes.
Other Identification of unexpected functional and nonfunctional PNETs have been found during abdominal MRI surveillance in individuals with TSC. Further monitoring and evaluation should be referred to endocrinology.

Recommendation Grading




Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management

Publication Month/Year

July 23, 2021

Last Updated Month/Year

June 9, 2022

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Male, Adolescent, Adult, Child

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Physician, nurse practitioner, nurse, genetics, physician assistant


Assessment and screening, Diagnosis, Management

Diseases/Conditions (MeSH)

D014402 - Tuberous Sclerosis


tuberous sclerosis complex (TSC), diagnostic criteria, surveillance and management guidelines


Number of Source Documents
Literature Search Start Date
May 10, 2018
Literature Search End Date
July 26, 2018