Tuberous sclerosis complex (TSC) is a complicated disorder that requires lifelong care from a variety of specialists. The TSC Alliance provides the resources below to connect healthcare providers with TSC experts and give them the resources to offer the highest quality of care to their patients.

If you have any questions or need more information about diagnosis, surveillance, and management of TSC, contact TSC Alliance Director, Medical Affairs Ashley Pounders, MSN, FNP-C, at apounders@tscalliance.org or by calling 1-800-225-6872.

Diagnosis, surveillance and management recommendations

The most current consensus guidelines are from the 2021 peer-reviewed publication and are available here.

Surveillance & management recommendations for TSC

For the Newly Diagnosed or Suspected TSC For Individuals Already Diagnosed with TSC

Obtain three-generation family history to assess for additional family members at risk of TSC. Offer genetic testing and family counseling if not performed previously.
Offer genetic testing for family counseling or when TSC diagnosis is in question but cannot be clinically confirmed.
Obtain magnetic resonance imaging (MRI) of the brain to assess for the presence of tubers, subependymal nodules (SEN), migrational defects, and subependymal giant cell astrocytoma (SEGA). Obtain magnetic resonance imaging (MRI) of the brain every 1 to 3 years in asymptomatic TSC patients younger than age 25 years to monitor for new occurrence of subependymal giant cell astrocytoma (SEGA). Patients with large or growing SEGA, or with SEGA causing ventricular enlargement but yet are still asymptomatic, should undergo MRI scans more frequently, and patients and 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.
During infancy, educate parents to recognize infantile spasms and focal seizures, even if none have occurred at the time of first diagnosis. Surgical resection should be performed for acutely symptomatic SEGA. Cerebral spinal fluid diversion (shunt) may also be necessary. Either surgical resection or medical treatment with target of rapamycin inhibitors (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 baseline routine electroencephalogram (EEG) while awake and asleep. If abnormal, especially if features of TSC-associated neuropsychiatric disorders (TAND) are also present, follow up with 8- to  24-hour video EEG to assess for seizure activity. Obtain routine electroencephalograph (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 hours 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. Adrenocorticotropic hormone (ACTH), synthetic ACTH or prednisolone can be used if treatment with full-dose vigabatrin for 2 weeks has not correlated with clinical improvement.
Antiseizure medications (ASMs) 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 ASMs, everolimus, cannabidiol, or dietary therapies over one another in specific subsets of patients.
Epilepsy surgery should be considered for medically refractory TSC patients at epilepsy surgery centers with expertise in TSC. Special consideration should be given to children at younger ages experiencing neurological regression and is best if performed at epilepsy surgery centers with experience and expertise in TSC.
Perform comprehensive assessment for TSC-Associated Neuropsychiatric Disorders (TAND) across all levels of potential TAND manifestations. Perform annual screening for TAND, using validated screening tools such as the TAND Checklist. 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 manifestation(s).
Refer as appropriate to suitable professionals to initiate evidence-based interventions based on the TAND profile of needs identified above Perform comprehensive formal evaluation for TAND across all levels of TAND at key developmental time points: infancy (0 to 3 years), preschool (3 to 6 years), pre-middle school (6 to 9 years), adolescence (12 to 16 years), early adulthood (18 to 25 years), and as needed thereafter.
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). 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).
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. 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 (IEP/IEDP).
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 wellbeing. 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.
Obtain MRI of the abdomen to assess for the presence of angiomyolipomas and renal cysts. Obtain MRI of the abdomen to assess for the progression of angiomyolipoma and renal cystic disease every 1 to 3 years throughout the patient’s lifetime.
Evaluate renal function by determination of glomerular filtration rate (GFR). Embolization followed by corticosteroids is 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 mTOR inhibitor is the recommended first-line therapy. Selective embolization or kidney-sparing resection are acceptable second-line therapy for asymptomatic angiomyolipoma.
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. Inquire about smoking, occupational exposures, connective tissue disease (CTD) symptoms, chyle leak, and pulmonary manifestations such as dyspnea, cough, and spontaneous pneumothorax in all adults at each clinic visit.
Perform baseline chest CT in all females, and symptomatic males, starting at the age of 18 years or older. For adult females with a negative screening CT who remain asymptomatic, obtain high resolution CT (HRCT) to screen for the presence of LAM every 5 years through menopause. Low-dose CT protocols preferred.
Perform baseline PFTs and 6MWT in patients with evidence of cystic lung disease consistent with LAM on the screening chest CT. For patients with evidence of cystic lung disease consistent with LAM on screening CT, obtain follow-up HRCT after 1 to 3 years, and on a case-by-case basis thereafter at least every 5 years depending upon the individual circumstances. Low-dose CT protocols preferred.
Perform routine serial PFT monitoring at least annually in patients with evidence of LAM on HRCT and more frequently in patients who are progressing rapidly or who are being monitored for response to therapy.
Use mTOR inhibitors 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 > 90ml/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.
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 PFTs to monitor adequacy of pharmacodynamic suppression of the mTOR pathway.
Perform a detailed clinical dermatologic inspection/exam. 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 mTOR inhibitor 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).
Perform a detailed clinical dental inspection/exam. Perform a detailed clinical dental inspection/exam 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). They 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.
Consider fetal echocardiography to detect individuals with high risk of heart failure after delivery when rhabdomyomas are identified via prenatal ultrasound. Obtain an echocardiogram every 1 to 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 an echocardiogram in pediatric patients, especially if younger than three years of age Obtain electrocardiogram 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.
Obtain an electrocardiogram in all ages to assess for underlying conduction defects.
Perform a complete ophthalmologic evaluation, including dilated fundoscopy, to assess for retinal findings (astrocytic hamartoma and achromic patch) and visual field deficits. 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 fundus examinations to detect retinal changes.
Identification of unexpected functional and nonfunctional pancreatic neuroendrocrine tumors (PNETS) have been found during abdominal MRI surveillance in individuals with TSC. Further monitoring and evaluation should be referred to endocrinology.


Reviewed by Ashley Pounders, MSN, FNP-C, Director of Medical Affairs, TSC Alliance, November 2023.

Clinical management of TSC

Because TSC affects multiple organs, diagnostic studies are recommended for all individuals with a new diagnosis of TSC regardless of their outward manifestations of the disease. For example, published recommendations for diagnostic and follow-up evaluations suggest baseline imaging using cranial MRI or CT regardless of the presence of neurological symptoms. This suggestion is because it is important to identify possible subependymal giant cell astrocytoma (SEGA), which has an increased growth potential over subependymal nodules (SEN) and therefore needs more extensive follow-up.

In order to ensure comprehensive care, referrals to a variety of specialists familiar with TSC should be coordinated. If possible, a referral to a multidisciplinary clinic specializing in TSC is ideal, as the center will likely house all necessary specialists, including a dermatologist, neurologist, geneticist, nephrologist and/or urologist, ophthalmologist and cardiologist.

The clinician making the diagnosis of TSC may recommend that other, at-risk family members also be evaluated for this condition. TSC is an autosomal dominant genetic disorder, and while all persons with TSC are thought to have symptoms, the presentation of their symptoms can be highly variable even within the same family. A determination of whether or not the parents and siblings of a diagnosed child are affected is important to the provision of later genetic counseling, thereby making an accurate diagnosis necessary. While an estimated two-thirds of individuals diagnosed with TSC are born into families with no prior history of the disease (i.e., sporadic mutation), it is becoming more and more common for adults to learn of their own diagnosis following the diagnosis of their child or because of other medical concerns.

There is some debate as to which evaluations are necessary when testing the parents of a newly diagnosed child. The consensus is that a thorough physical examination conducted by a physician familiar with TSC will detect the majority of affected individuals.  The evaluation should include a skin examination with a Woods lamp (ultraviolet light) and a retinal examination through dilated pupils.  Further examination via diagnostic imaging of the brain and kidneys should be ordered for the parents of children with TSC and/or for adults with medical issues that suggest a diagnosis of TSC. Diagnostic molecular testing should also be discussed with the parents of a newly diagnosed child and/or adults suspected or diagnosed with TSC.

Reviewed by Ashley Pounders, MSN, FNP-C, Director of Medical Affairs, TSC Alliance, November 2023.

Diagnostic criteria

The clinical and genetic diagnostic criteria of 2021 are summarized below:

Hypomelanotic macules (≥3; at least 5mm diameter) “Confetti” skin lesions
Angiofibroma (≥3) or fibrous cephalic plaque Dental enamel pits (>3)
Ungual fibromas (≥2) Intraoral fibromas (>2)
Shagreen patch Retinal achromatic patch
Multiple retinal hamartomas Multiple renal cysts
Multiple cortical tubers and/or radial migration lines Nonrenal hamartomas
Subependymal nodule (≥2) Sclerotic bone lesions
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma
Lymphangioleiomyomatosis (LAM)*
Angiomyolipomas (>2)*
Definite TSC:  2 major features or 1 major feature with 2 minor features.
Possible TSC:  either 1 major feature or >2 minor features.
* a combination of the 2 Major clinical features LAM and angiomyolipomas without other features does not meet criteria for a definite diagnosis.
Genetic diagnosis: A pathogenic variant in TSC1 or TSC2 is diagnostic for TSC. Most TSC-causing variants are sequence variants that clearly prevent TSC1 or TSC2 protein production. Some variants compatible with protein production (e.g., some missense changes) are well established as disease-causing. Other variant types should be considered with caution.


Approximately 15% of individuals with TSC have no pathogenic variant, sometimes called a mutation, identified by conventional genetic testing, and a normal result does not exclude TSC or have any effect on the use of Clinical Diagnostic Criteria to diagnose TSC.  Clinical genetic testing identifies pathogenic variants in approximately 85% of DNA samples submitted for testing from individuals who have a definite diagnosis of TSC based on accepted diagnostic criteria. For the remaining 15%, there are several explanations for why we may not find a pathogenic variant. One explanation is genetic mosaicism, in which a pathogenic variant in the TSC1 or TSC2 gene is present in some of the individual’s cells but not all of the cells in the body. Another reason we may not find a pathogenic variant is that the genetic mutation may have occurred in sections of the gene that we do not test because we do not understand how changes in these parts of the genes can cause disease.

Reviewed by Ashley Pounders, MSN, FNP-C, Director of Medical Affairs, TSC Alliance, November 2023.


TSC Clinics

The TSC Alliance has offered TSC Clinic designations to the institutions listed here to help serve as a resource for the TSC community to identify where comprehensive clinical care for people with TSC is available.

The TSC Alliance does not accredit any TSC Clinic or TSC Center of Excellence, and the TSC Alliance does not directly provide or guide any clinical care or medical decision-making.  None of the information provided by TSC Alliance, including the identification of TSC Clinics or TSC Centers of Excellence, is intended as medical advice and should not be relied upon as a substitute for professional consultation with a qualified healthcare provider familiar with a patient’s medical needs.  The identification of a TSC Clinic or Center of Excellence does not constitute a recommendation or endorsement of any provider of medical care.

Peer-to-peer listserv

The TSC Alliance invites healthcare professionals affiliated with a TSC Clinic, TSC Center of Excellence, or University Medical Center to subscribe to our new private listserv: p2p@lists.tscalliance.org. Its primary purpose is for members to pose TSC-related cases or questions to their peers for feedback. Members may also use the listserv to seek opportunities for collaboration on TSC-related projects. The listserv will be monitored to ensure it is being used for appropriate communications.

Please note: This listserv is meant for healthcare professionals ONLY. For all general TSC information, you can reach out to our support navigators at support@tscalliance.org. Healthcare providers can reach out to Ashley Pounders, MSN, FNP-C at apounders@tscalliance.org for any questions.

How to subscribe

Email Ashley Pounders at apounders@tscalliance.org who will add you as a member. You should receive a “Welcome to list p2p” email from Groups List Manager p2p-request@lists.tscalliance.org to confirm your membership.

Key medical publications

The following papers are available free of charge with open access to anyone in the world.  The TSC Alliance encourages sharing these links, or a link to this page (tscalliance.org/consensus) with healthcare providers.  Any future updates to these recommendations will also be posted on this page.

Updated 2021 clinical consensus guidelines

Updated TAND clinical consensus guidelines

CME opportunities

Improving outcomes for patients with tuberous sclerosis complex-associated seizures: Integrating new treatment options into existing care pathways (expires December 8, 2024)

In this activity, a pediatric neurologist and epilepsy specialist, along with another epilepsy specialist involved in managing patients with TSC, share their insights on the current management strategies for TSC-associated seizures and the potential for preventing or delaying seizures in patients with TSC, and review emerging treatment options. Plus, hear from a caregiver of a patient with TSC on her experience and how novel treatments may improve outcomes.

This activity is jointly provided by USF Health and touchIME.

Professional Advisory Board

The TSC Alliance’s Professional Advisory Board (PAB) is composed of clinicians from diverse specialties serving individuals across the age spectrum and constituent representatives, who respond to and make recommendations to meet the evolving medical needs of individuals and families affected by TSC (e.g., clinical care barriers, clinical trial recruitment/enrollment/equitable representation, changes in health policy). Toward this end, the Board of Directors approved ten members of this new PAB on February 29, 2024. This group will be asked to suggest additional nominees for PAB membership to fill gaps in expertise and representation.

Current Professional Advisory Board Members

Lisa Carlton, PhD
Washington, DC

Peter Crino, MD, PhD
Adult Neurology and Epilepsy
Baltimore, MD

Thomas Darling, MD, PhD
Rockville, MD

Jennifer E. Glass, LGC
Genetic Counseling
Cincinnati, OH

Jonathan Goldstein
New York, NY

Dana Holinka
Northglenn, CO

Brigett Langstaff
Baldwinsville, NY

Elahna Paul, MD, PhD
Nephrology and Pediatric Kidney Transplant
Boston, MA

Penney Parkes
Greenwich, CT

Stephanie Randle, MD, MS
Pediatric Neurology and Epilepsy
Seattle, WA