Authors: Mary Jeno, MD; Sreenath Thati Ganganna, MD, MBBS Reviewed: July 2021 Tuberous sclerosis complex (TSC) is a rare genetic disorder in which noncancerous tumors grow in important organs. For example, they may grow in the brain, eyes, lungs, skin, heart, and kidneys. Symptoms can vary depending on the organs involved. TSC is often diagnosed in a newborn or in infancy. However, in very mild cases, it may not be noticed until later in childhood or even adulthood. Most cases of TSC are due to a mutation in the TSC1 or TSC2 genes. TSC appears in about 1 in 5,000 to 10,000 live births. Males and females seem to be affected equally. The disease is lifelong. There is no cure for TSC, but there is treatment for the symptoms caused by the growths. TSC leads to growths, or noncancerous tumors, called “hamartomas.” Hamartomas can impact the function of the organ they are growing in. This impact will be based on the size of the growth and its location. Cancerous tumors are rare in TSC. TSC is unique for each person. It is difficult to predict who will develop growths and where they will occur. However, growths most commonly appear in a particular set of locations. These locations include: Because of all this variation, the spectrum of clinical features can also range from mild at one end to severe or prominent at the other. For this reason, the age at diagnosis may vary: Most patients with TSC will be diagnosed with other medical problems caused by the condition. Complications can include: TSC can cause serious or life-threating complications depending upon where the tumors grow and how big they are. For example: TSC is diagnosed on the basis of: Diagnosis can be confirmed in two ways. A variety of distinctive features can confirm TSC. These features include: These can appear as: Growths in the brain are detected with imaging studies such as brain MRI. They may include: Some people with TSC have normal development. However, typically, people with TSC have developmental delays or intellectual disability. Developmental delays are often seen in early childhood. They appear as delayed achievement of developmental milestones. Parents and teachers may also notice hyperactivity or behavioral problems in children with TSC. These are another common finding. Benign growths of the kidney include angiomyolipomas and renal cysts. They can cause high blood pressure, back pain, or blood in urine. These are also called cardiac rhabdomyomas. They are most often found in infants. They are diagnosed with an ultrasound of the heart (echocardiogram). They typically shrink as infants get older, or by around age 2. Heart tumors can obstruct blood flow in heart or cause heart rhythm problems. They may also remain silent, not causing any problems. These mostly consist of white growths at the back of the eye called retinal astrocytic hamartomas. They rarely affect vision. Subtle findings in patients with TSC include: Sometimes, signs of TSC are missed. This is true particularly if However, it is usually difficult to miss TSC due to the number of organs that may be involved. TSC is, in fact, often discovered with the use of ultrasound in a fetus during pregnancy. About 75% to 80% of patients with TSC have a mutation in either the TSC1 or TSC2 gene. These genes provide instructions to make a protein that helps control cell growth and reproduction. When these genes are affected, an individual develops the tendency to form hamartomas (growths). Most TSC patients with a defective gene have de novo genetic mutations. De novo mutations are spontaneous. They are new, rather than inherited from a parent. They occur in eggs, sperm, or fertilized eggs. Some TSC patients—about 20%—inherited a defective TSC1 or TSC2 gene from a mother or father. Several types of lab tests are used in TSC. These include: This is helpful in confirming a diagnosis. Most people with TSC have a mutation in the TSC1 or TSC2 genes. However, a negative genetic test does not rule out TSC. In some patients, a TSC diagnosis can only be established clinically. MRI is helpful in taking detailed pictures of the brain. This can help detect abnormal brain growths. It can also be used to detect lung tumors. Ultrasound can scan the kidneys for tumors. An ultrasound of the heart is called an echocardiogram. It can detect rhabdomyoma, a benign tumor of the heart muscle. A CT scan can look at the chest to detect lung tumors. An eye exam performed by an ophthalmologist can detect tumors inside the eye. An EEG reads the electrical activity of the brain. It may be used if a child has seizures. It can help identify the type and location of the seizures. This test uses painless electrodes placed on the surface of the scalp. Tests are typically repeated either every year or every few years: MRI scan of the brain is obtained at least once per year in children who have seizures, neurologic problems, or previous growths seen on imaging. Needed every 1 to 3 years for evaluation of the kidneys. Needed every year until any heart tumors go down in size. Should be performed annually. Should be performed annually. Repeated based on a patient’s seizure activity. Treatment of TSC is based on the type and severity of the symptoms. It therefore varies from patient to patient. Seizures in TSC patients are usually treated with standard antiseizure medications. Some patients have a special type of seizure called infantile spasms. These patients need specific treatments. Sometimes, seizures do not respond to antiseizure medications. In these cases, surgery may be used to remove the brain tubers that may be causing them. In rare cases, cancerous growths can occur in the brain. These growths can block spinal fluid. They may be treated with: Other TSC-related conditions that may require treatment include: The team involved in treating patients with TSC is usually very large. It can include: Treat seizures and monitor brain imaging studies. Do school and IQ testing to ensure children are receiving all the services they need to do their best in school. Can be helpful for managing behavioral problems. May help remove seizure–causing growths or cancerous growths in the brain. Monitor for kidney growths and subsequent issues, such as high blood pressure. Monitor heart function and any growths seen on echocardiogram. Monitor for any lung growths or related complications. Are a primary resource for all children. They can help navigate the services and referrals these children may need. It is not possible to outgrow TSC. It is a lifelong diagnosis. Outcomes are dependent on many factors. Many children with TSC can attend school and participate in sports and activities. It is likely that learning and development will be delayed. However, this will affect each child differently. It is challenging to predict how each child will develop. Children will likely require some assistance in school. This could include things such as: Adulthood outcomes will vary based on the severity of the disease. Often, children with TSC grow into healthy, independent adults. They can live full lives with the help of appropriate treatments. However, some will continue to experience disabling seizures, developmental delay, or intellectual disability. They will require special assistance. TSC will affect the family dynamic in several ways. It requires: The goal of treatment is to help a child with TSC live a full and meaningful life both in the family setting and in the social setting. Diets such as the ketogenic diet may be used for seizure maintenance. However, dietary and lifestyle changes do not impact the disease itself. Still, it is important for all children and adults to stay active and work on healthy lifestyle choices. TSC Alliance Infantile Spasms Action Network Pediatric Epilepsy Surgery Alliance In addition, PESA has resources for medical professionals to assist in helping clinicians help the parents of their patients find the resources they need after surgery. Educators and therapists will also find helpful resources and information, including videos, guides, and relevant research. Patients who have undergone surgery are encouraged to register with the Global Pediatric Epilepsy Surgery Registry to help set future research priorities. JCN Podcast on Tuberous Sclerosis Child Neurology Foundation (CNF) solicits resources from the community to be included on this webpage through an application process. CNF reserves the right to remove entities at any time if information is deemed inappropriate or inconsistent with the mission, vision, and values of CNF. ClinicalTrials.gov for Tuberous Sclerosis Complex are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently. ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details. Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits. A tuberous sclerosis complex (TSC) diagnosis can be overwhelming, and many people say they feel alone. “Your Journey with Tuberous Sclerosis Complex (TSC) — You Are Not Alone”, a video from the TSC Alliance, features interviews with parents who have children with TSC as well as adults with TSC and TSC Alliance staff members, who each explain why you are not alone in the journey of TSC. The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only. CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. Northrup H, Koenig MK, Pearson DA, et al. Tuberous Sclerosis Complex. 1999 Jul 13 [Updated 2020 Apr 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1220/ Goodman M, Lamm SH, Engel A, et al. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol. 1997 Feb. 12(2):85-90. PMID: 9075016; https://doi.org/10.1177/088307389701200203 Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct. 49(4):243-54. PMID: 24053982; https://doi.org/10.1016/j.pediatrneurol.2013.08.001 Au KS, Williams AT, Gambello MJ, Northrup H. Molecular genetic basis of tuberous sclerosis complex: from bench to bedside. J Child Neurol. 2004 Sep;19(9):699-709. PMID: 15563017; https://doi.org/10.1177/08830738040190091101 Stephanie Rnadle, MD, MS, et al. Tuberous sclerosis complex: Genetics, clinical features, and diagnosis. In: UpToDate, Waltham, MA. (Accessed on June 28, 2021). https://www.uptodate.com/contents/tuberous-sclerosis-complex-genetics-clinical-features-and-diagnosis Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006 Sep 28;355(13):1345-56. PMID: 17005952; https://doi.org/10.1056/NEJMra055323
University of Iowa, Stead Family Children’s Hospital, Iowa City, IA SUMMARY
JUMP TO
Disorder Overview
DESCRIPTION
Variability
Complications
SIGNS AND SYMPTOMS
Skin abnormalities
Brain abnormalities
Developmental delays
Kidney growths
Heart tumors
Eye findings
CAUSES
LAB INVESTIGATIONS
Genetic testing
Magnetic resonance imaging (MRI)
Ultrasound
Echocardiogram
Computerized tomography (CT) scan
Eye exam
Electroencephalogram (EEG)
MRI of brain
MRI of abdomen
Echocardiogram
Skin checks
Eye exam
EEG
TREATMENT AND THERAPIES
Treating Seizures
Treating Cancerous Growths
Treating Other Conditions
Treatment Team
Neurologists
Neuropsychologists
Psychologists
Neurosurgeons
Nephrologists
Cardiologists
Pulmonologists
Primary care pediatricians
OUTLOOK
Childhood
Adulthood
Family Dynamic
Diet and Lifestyle
Resources
Organizations
The TSC Alliance is dedicated to finding a cure for tuberous sclerosis complex, while improving the lives of those affected. The TSC Alliance was founded on the core belief that community is a sustaining strength in the face of difficult challenges.
The TSC Alliance hosts a private Facebook group, TSC Alliance Tuberous Sclerosis Complex Discussion Group with over 10,000 members. This discussion group is made available for caregivers, family members and other interested parties to discuss the various aspects of dealing with tuberous sclerosis complex.
The Infantile Spasms Action Network (ISAN) is a collaborative network of over 30 national and international entities focused on raising awareness for infantile spasms. To learn more about the group please visit their website.
The Pediatric Epilepsy Surgery Alliance (formerly known as The Brain Recovery Project) enhances the lives of children who need neurosurgery to treat medication-resistant epilepsy. They empower families with research, support services, and impactful programs before, during, and after surgery. PESA’s programs include research-based, reliable information to help parents and caregivers understand when a child’s seizures are drug-resistant; the risks and dangers of seizures; the pros and cons of the various neurosurgeries to treat epilepsy; the medical, cognitive, and behavioral challenges a child may have throughout life; school, financial aid, and life care issues. PESA’s resources include a comprehensive website with downloadable guides, pre-recorded webinars, and virtual workshops; an informative YouTube channel with comprehensive information about epilepsy surgery and its effects; a private Facebook group (Education After Pediatric Epilepsy Surgery) with over 300 members; Power Hour (bi-monthly open forums and live virtual workshops on various topics); and free school training to help your child’s education team understand the impact of their epilepsy surgery in school. Their Peer Support Program will connect you with a parent who has been there. The Pediatric Epilepsy Surgery Alliance also hosts biennial family conferences and regional events that allow families to learn from experts, connect with other families, and form lifelong friendships. They also provide a travel scholarship of up to $1,000 to families in need to fund travel to a level 4 epilepsy center for a surgical evaluation.Publications
Podcast from SAGE Neuroscience and Neurology/Journal of Child Neurology (JCN). Dr. Alison Christy speaks with Dr. Jurriaan Peters of Boston Children’s Hospital about their article published in JCN “The Evolution of Subclinical Seizures in Children With Tuberous Sclerosis Complex”. Then Dr. Christine Park of Brooke Army Medical Center in San Antonio gives an overview of the disease. Finally, Dr. Alison Christy interviews Dr. Derek Bauer of the University of Virginia on their personal connection with the disease as well as their career path. Research
Family Stories
References
‹ Return to Disorder Directory