Years published: 1984, 1985, 1987, 1988, 1989, 1990, 1992, 1993, 1994, 1997, 1998, 1999, 2000, 2004, 2005, 2016, 2019, 2023
NORD gratefully acknowledges Francis J. DiMario Jr., MD, Department of Pediatrics, Neurogenetics-Tuberous Sclerosis Clinic, Connecticut Children’s Medical Center, for assistance in the preparation of this report.
Tuberous sclerosis is a rare genetic multisystem disorder that is typically apparent shortly after birth. The disorder can cause a wide range of potential signs and symptoms and is associated with the formation of benign (non-cancerous) tumors in various organ systems of the body. The skin, brain, eyes, heart, kidneys and lungs are frequently affected. These tumors are often referred to as hamartomas. Hamartoma is a general term for a tumor or tumor-like growth that is made up of cells normally found in the area of the body where the hamartoma forms. Hamartomas are not malignant; they do not typically metastasize and spread to other areas of the body. However, these abnormal growths can grow larger and can damage the affected organ system. The number, size, and specific location of these abnormal growths in individuals with tuberous sclerosis can vary widely and consequently the severity of the disorder can vary widely as well. Tuberous sclerosis results from alterations (mutations) in a gene or genes that may occur spontaneously (sporadically) for unknown reasons or be inherited as an autosomal dominant trait. Most cases represent new (sporadic or de novo) gene mutations, with no family history of the disease. Mutations within at least two different genes are known to cause tuberous sclerosis, the TSC1 gene or the TSC2 gene.
Tuberous sclerosis is a highly variable disorder. The signs, symptoms, and severity of the disorder can vary dramatically from one person to another, even among members of the same family. This is due, in part, to the specific organ systems that are involved. Any organ system of the body can be affected. Tuberous sclerosis can cause mild disease in which individuals go undiagnosed into adulthood or it can cause significant complications that can impact quality of life or the disorder can cause potentially severe, life-threatening complications.
Because of the highly variable nature of the disorder, it is important to note that affected individuals may not have all of the symptoms discussed below and that the disorder’s expression and progression will be unique in every individual person. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.
Nearly all individuals with tuberous sclerosis develop abnormalities of the skin. Many infants have white patches or spots (hypomelanotic macules) on their skin at birth or early during infancy. These abnormal patches of skin can vary in size and shape and sometimes may be quite small and difficult to notice on infants with fair skin. They occur most often on the arms, legs and trunk of the body. The macules may be distinctly white or may appear lighter in color in relation to the surrounding skin.
Small bumps or red spots known as angiofibromas may appear between the ages of 3 and 5 years, primarily on the face and often in a butterfly pattern. The small bumps generally become more numerous and larger as children grow older (until they reach adolescence). Some individuals will develop an irregularly-shaped, thickened, flesh-colored skin rash called a shagreen patch. This rash or plaque of abnormal skin usually develops on the lower back and is sometimes described as having the texture or feel of an orange peel, e.g. rough and dimpled.
Raised, thickened areas of skin called fibrous plaques may develop on the forehead and, less often, the scalp or cheeks. When on the scalp, these lesions may occur with the loss of nearby hair or be surrounded by thick, white hair. Adolescents and adults may develop small benign tumors around or under the nail beds of the fingers or toes (ungual fibroma).
The central nervous system is frequently involved in individuals with tuberous sclerosis. Central nervous system tumors can include subependymal nodules (SENs), cortical dysplasias, and subependymal giant cell astrocytomas or SEGAs. SEGAs occur in approximately 5%-15% of affected individuals and can cause pressure and obstruction within the brain. More than 80% of individuals with tuberous sclerosis develop seizures during childhood. Many initially manifest infantile spasms during infancy, which are characterized by a sudden jerk with flexion at the waist and raising of the arms. Alternatively, other seizure types can occur such as focal seizures involving part of the body or altered awareness, in which there is abnormal electrical activity in one specific area of the brain or generalized seizures where whole body convulsions or drop attacks develop that are associated with abnormal electrical activity throughout the brain. Most individuals will develop seizures at some point during life and most seizure types have been associated with tuberous sclerosis.
Affected individuals may have normal development and cognitive function but a majority experience delays in reaching developmental milestones (developmental delays) and have some degree of intellectual disability. Individuals can potentially develop a range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), sleep disturbances or disorders, learning and cognitive impairments, or behavioral issues including disruptive and emotional behaviors or problems. The term TSC-associated neuropsychiatric disorders (TANDs) may be used to describe the interrelated, collective behavioral, psychiatric, intellectual, academic, neuropsychological, and psychosocial abnormalities potentially associated with the disorder.
Brain tumors, especially SEGAs, can also cause hydrocephalus by blocking the flow of cerebrospinal fluid (CSF) within the brain. Hydrocephalus is characterized by the accumulation of excess amounts of CSF in and around the brain. The accumulation of CSF within the skull puts abnormal pressure on the brain and can cause a variety of symptoms including headaches, nausea, vomiting, irritability, and behavioral changes.
Another form of tumor associated with tuberous sclerosis is a benign angiomyolipoma. These tumors are made up of fat, blood vessels and smooth muscle cells, usually affect the kidneys, and may not cause any symptoms (asymptomatic). In some instances, they may cause flank pain or kidney (renal) dysfunction. Angiomyolipomas are prone to rupturing and bleeding (hemorrhaging), which can potentially become life-threatening (approximately 20% of the time). Around 70% of affected children may develop a benign angiomyolipoma, usually in later childhood or adolescence. In rare instances, angiomyolipomas or cysts may be found outside of the kidneys such as in the liver. Usually, these growths do not cause any symptoms.
Some women with tuberous sclerosis develop lymphangioleiomyomatosis (LAM), a condition in which the spread and uncontrolled growth (proliferation) of specialized cells (smooth muscle cells) form progressive cystic cavities within the lungs resulting in shortness of breath, coughing, and/or difficulty breathing (dyspnea), especially following periods of exercise or exertion. LAM mostly occurs in women of childbearing age and is extremely rare in men.
Some individuals may develop multifocal micronodular pneumocyte hyperplasia (MMPH), a condition in which multiple nodules form throughout the lungs because of the abnormal proliferation of certain lung cells called pneumocytes. MMPH usually is not associated with any symptoms, but there have been at least two reports in the medical literature of breathing difficulties and eventually respiratory failure associated with MMPH.
In addition to difficulty breathing, the lung complications associated with tuberous sclerosis can cause a collapsed lung (pneumothorax) and chylothorax, a condition in which there is an accumulation of chyle in the space between the membranes (pleura) that line the lungs and chest cavity. Chyle is a milky fluid that consists of lymph and emulsified fats. Chylothorax can cause difficulty breathing, rapid breathing (tachypnea), chest pain, or respiratory compromise.
A benign tumor known as a rhabdomyoma can develop in the heart of infants and young children. The tumor initially forms before birth (antenatally) in the developing fetus. These tumors usually do not cause symptoms and may regress on their own and disappear over time. In some instances, they can interfere or obstruct the flow of blood from the heart (outflow tract obstruction) and/or cause irregular heartbeats (arrhythmias).
Another common finding is the formation of small growths or tumors on the retina, the light-sensitive membrane that coats the inside of the eyes (multiple retinal hamartomas). These tumors rarely cause problems and seldom affect vision.
Some signs and symptoms associated with tuberous sclerosis occur less often than those described above. These findings are referred to as minor features of the disorder. Such symptoms include patches or areas of lightened color or a lack of color affecting the retina due to pigment loss (retinal achromatic patch). Some individuals may develop pitting or tiny holes in the enamel of teeth (dental enamel pitting) or the formation of fibrous growths within the mouth (intraoral fibromas), particularly in the gums. In some instances, individuals may develop “confetti” skin lesions during childhood, early adolescence, or adulthood. These lesions are tiny (1-3 millimeters) spots that are lighter in color (hypopigmented) than the surrounding skin. They may be scattered across certain areas of the skin.
Renal cysts, sometimes referred to as epithelial cysts, occur in approximately 20-30% of individuals and usually do not cause symptoms. These small, fluid-filled cysts can, in some instances, result in increased blood pressure. If the kidneys are filled with cysts, kidney dysfunction and kidney failure can eventually develop. Individuals with tuberous sclerosis may have a greater risk of developing certain cancers of the kidney than the general population, although their overall occurrence is still very uncommon. Less than 3% of individuals may eventually develop renal cell carcinoma. In extremely rare instances (less than 1%), an oncocytoma or a malignant angiomyolipoma may occur.
Some affected individuals will develop neuroendocrine tumors (NETs). Neuroendocrine tumors arise from hormone-producing cells of the neuroendocrine system. These cells are a cross or combination of endocrine cells and nerve cells. They are found throughout the body and perform many functions such as regulating air and blood flow through the lungs.
Tuberous sclerosis is caused by an alteration (mutation) in one of two different genes, the TSC1 gene or the TSC2 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain. Generally, alterations in the TSC2 gene result in a more severe disease expression.
In many instances, an alteration causing tuberous sclerosis occurs as a new (sporadic or de novo) mutation, which means that the gene alteration has occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. The disorder is not inherited from or “carried” by a healthy parent. However, such alterations can also be passed on through dominant inheritance (where a trait is transmitted from either an affected mother or father to their child).
Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
The TSC1 gene is located on the long arm (q) of chromosome 9 (9q34); the TSC2 is located on the short arm (p) of chromosome 16 (16p13.3). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.
The TSC1 gene regulates (encodes for) production of a protein known as hamartin that is thought to function as a tumor suppressor. The TSC2 gene encodes for a different tumor suppressor protein known as tuberin. A tumor suppressor gene is a gene that slows down cell division, repairs damage to the DNA of cells, and/or tells cell when to die, a normal process called apoptosis. Hamartin and tuberin are believed to inhibit the activity of a chemical pathway in the body called the mammalian target of rapamycin or mTOR pathway. Such a chemical pathway involves a number of complex interactions and is critical for normal human development; the mTOR pathway regulates the creation (synthesis) of proteins that are involved in many cellular functions including cell growth, proliferation, and survival. Alterations in the TSC1 and TSC2 genes ultimately lead to the uncontrolled activity or “hyperactivation” of the mTOR pathway and, consequently, to the development of the tumors that characterize tuberous sclerosis.
Tuberous sclerosis is a rare genetic disorder that affects 1 in 6,000 newborns in the United States. Approximately 40,000 to 80,000 people in the United States have tuberous sclerosis. The prevalence in Europe is estimated to be approximately 1 in 25,000 to 1 in 11,300. As many as 2 million people worldwide are believed to have the disorder. Males and females are affected in equal numbers and the disorder occurs in all races and ethnic groups.
A diagnosis of tuberous sclerosis is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation, and a variety of specialized tests. For example, the presence of hypopigmented macules on the skin occurring along with seizures or autism are diagnostic clues for tuberous sclerosis. Clinical diagnostic criteria have been established and updated for tuberous sclerosis (Northrup et al. 2018).
Generally, a diagnosis is considered definitive in individuals with two or more major features or one major feature and two or more minor features of the disorder. A possible diagnosis is suspected when one major feature or two or more minor features are present.
In some instances, a cardiac rhabdomyoma can be detected before birth (prenatally).
Clinical Testing and Workup
Molecular genetic testing can confirm a diagnosis of tuberous sclerosis. Molecular genetic testing can detect alterations in one of the two genes known to cause the disorder, and is available as a diagnostic service at specialized laboratories.
A variety of tests can be used to help obtain a diagnosis of tuberous sclerosis or to assess or establish the extent of the disorder in an individual. Such tests include computerized tomography (CT) scanning and magnetic resonance imaging (MRI) to evaluate the brain for the presence of tumors or other brain involvement. An MRI can also be used to evaluate the kidneys or liver for the presence of tumors. A high resolution CT scan can be used to evaluate the lungs. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues.
An echocardiogram and an electrocardiogram (EKG) can be used to evaluate the heart for the presence of a rhabdomyoma. During an echocardiogram, sound waves are directed toward the heart, enabling physicians to study cardiac function and motion. An electrocardiogram records the heart’s electrical impulses and may reveal abnormal electrical patterns.
Treatment may require the coordinated efforts of a team of specialists. Pediatricians and general internists, neurologists, dermatologists, cardiologists, dental specialists, eye specialists, psychiatrists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. Genetic counseling will be of benefit for affected individuals and their families.
The treatment for tuberous sclerosis is supportive and symptomatic. Early developmental intervention is important to ensure that affected children reach their potential. Most affected children will benefit from occupational, physical and speech therapy. Various methods of rehabilitative and behavioral therapy may be beneficial. It is essential that therapies are continued on a year-round basis to promote development of new skills and to prevent regression. Additional medical, social and/or vocational services including special remedial education may be necessary. Psychosocial support for the entire family is essential as well.
Anti-seizure drugs (anticonvulsants) may be prescribed to control seizures. The specific drug that is used will depend on several factors including the specific type of seizure, an affected individual’s age, other organ systems that are affected, and the severity of symptoms. Conventional anticonvulsants drugs that may be administered include phenobarbital, Dilantin (phenytoin), Klonopin (clonazepam), Depakene/Depakote (valproic acid/divalproex sodium), Tegretol (carbamazepine), Trileptal (oxcarbazepine), Topamax (topiramate), Lamictal (lamotrigine), Zonegran (zonisemide), Vimpat (lacosamide), Banzel (rufinamide), Onfi (clobazam), and others. All these anticonvulsants have potential side effects and require careful monitoring by a physician.
Two drugs have been approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of seizures associated with tuberous sclerosis. FDA approved Afinitor (everolimus) for the treatment of seizures in adult and pediatric patients aged 2 years and older with tuberous sclerosis in 2018, and Epidiolex (cannabidiol) for patients one year and older in 2020.
Sabril (vigabatrin) was approved in 2009 by the FDA to treat infantile spasms in children ages 1 month to 2 years. Treatment of children with tuberous sclerosis and infantile spasms with vigabatrin has been found to be effective. Visual field loss is an important safety concern with the use of this medication. The FDA has also approved adreno-corticotrophic hormone or ACTH (Acthar gel) for the treatment of infantile spasms. This medication has also been used to treat infants with tuberous sclerosis. These medications are used cautiously because of their side effects.
No specific anti-seizure medication works for all affected individuals. Often, a combination of different drugs may be required to treat some individuals. Alternative treatments include the ketogenic diet or the glycemic diet. Sometimes, seizures can be difficult to treat and medications or diets that initially worked will no longer provide benefit (refractory seizures). In some instances, seizure surgery to remove areas of brain dysplasia may be necessary to help to control seizures that don’t respond or stop responding to medications. Less invasive surgical options to control seizures include the implanting of a vagal nerve stimulator (VNS device). This is a small electrical stimulator placed under the skin over the upper chest and connected to one vagal nerve in order to provide intermittent electrical stimulus, like a pacemaker to the brain.
Surgery of other organs may be necessary if the ability of a particular organ to function properly is impaired by the presence of a tumor. For example, the obstruction of cerebrospinal fluid (CSF) circulation inside the brain (intracranial hypertension) because of a benign tumor may require a shunting procedure to drain the liquid or the surgical removal of the tumor.
In 2012, the FDA approved the use of Afinitor (everolimus) for the treatment of children and adults with tuberous sclerosis who have a subependymal giant cell astrocytoma that cannot be removed or can be only partially removed by surgery. The FDA also approved everolimus for the treatment of adults with tuberous sclerosis who have an angiomyolipoma of the kidney that does not require surgery right away. In some instances, angiomyolipomas will require surgery or embolization therapy. Cutting off the blood supply (arterial embolization) to a kidney tumor may be used to shrink down the size of the tumor. Embolization is usually followed by treatment with corticosteroids and surgical removal (resection) of the tumor that spares the kidney or by destruction (ablation) of the tumor. Large cystic lesions of the kidneys may also require surgical decompression or removal.
A benign tumor inside the heart (rhabdomyoma) may not cause symptoms and generally does not require treatment as they often regress on their own within the first several years after birth. If symptomatic, however, surgical removal (resection) may be necessary. Reports in the medical literature have detailed the off-label use of mTOR inhibitors to treat these tumors with positive results. Some affected individuals may be prescribed certain medications to treat irregular heartbeats (arrhythmias).
Individuals taking mTOR inhibitors for internal tumors (e.g. SEGAs or angiomyolipomas) may see improvement in skin lesions. The FDA has also approved a topical treatment for facial angiofibroma associated with TSC. Available evidence suggests that topical sirolimus 0.2% as the most effective in terms of clinical improvement. Individuals with no immediate indication for mTOR inhibitor treatment may undergo certain procedures to improve the appearance of skin lesions including dermabrasion, laser therapy, or surgical removal (excision) of a lesion.
In 2015, the FDA approved the use of mTOR inhibitors for the treatment of lung complications such as LAM in individuals with tuberous sclerosis. Because LAM occurs most often in young women of childbearing age, researchers have speculated that female hormones such as estrogen play a role in the development of the disorder. A link between LAM and female hormones has not been proven. However, many physicians have explored the use of agents that lower the production or effects of estrogen in the body. The results have varied greatly among individuals. Such agents may include medroxyprogesterone acetate. Estrogen-containing medications and dietary supplements should be discontinued in patients with LAM.
Supplemental oxygen therapy may be necessary for some individuals with impaired lung function. In individuals with severe lung disease that is resistant to treatment, a lung transplant may ultimately become necessary.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
De Vries PJ. Targeted Treatments in Tuberous Sclerosis (TSC). In: Treatment of Neurodevelopmental Disorders, Hagerman RJ, Hendren RL, editors. 2014 Oxford University Press, New York, NY. Pp. 177-214.
Byars AW. Tuberous Sclerosis Complex. In: Pediatric Neuropsychology: Research, Theory, and Practice, 2nd edition. Yeates KO, Ris MD, Taylor HG, Pennington BF, editors. 2010 The Guilford Press, New York, NY. Pp. 167-180.
Kwiatkowski DJ. Tuberous Sclerosis. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:595-6.
Lin YT, Yu CL, Tu YK, Chi CC. Efficacy and safety of topical mechanistic target of rapamycin inhibitors for facial angiofibromas in patients with tuberous sclerosis complex: A systematic review and network meta-analysis. Biomedicines. 2022;10(4):826. Published 2022 Mar 31. doi:10.3390/biomedicines10040826
Curatolo P, Moavero R, Roberto D, Graziola F. Genotype/phenotype correlations in tuberous sclerosis complex. Semin Pediatr Neurol. 2015;22:259-273. http://www.ncbi.nlm.nih.gov/pubmed/26706013
Sadowski K, Kotulska K, Schwartz RA, Jozwiak S. Systemic effects of treatment with mTOR inhibitors in tuberous sclerosis complex: a comprehensive review. J Eur Acad Dermatol Venereol. 2015;[Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/26403211
DiMario FJ Jr, Sahin M, Ebrahimi-Fakhari D. Tuberous sclerosis complex. Pediatr Clin North Am. 2015;62:633-648. http://www.ncbi.nlm.nih.gov/pubmed/26022167
De Vries PJ, Whitemore VH, Leclezio L, et al. Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND checklist. Pediatr Neurol. 2015;52:25-35. http://www.ncbi.nlm.nih.gov/pubmed/25532776
Teng JM, Cowen EW, Wataya-Kaneda M, et al. Dermatologic and dental aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements. JAMA Dermatol. 2014;150:1095-1101. http://www.ncbi.nlm.nih.gov/pubmed/25029267
Julich K, Sahin M. Mechanism-based treatment in tuberous sclerosis complex. Pediatr Neurol. 2014;50:290-296. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959246/
Franz DN, Belousova E, Sparagana S, et al. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomized EXIST-1 study. Lancet Oncol. 2014;15:1513-1520. http://www.ncbi.nlm.nih.gov/pubmed/25456370
Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49:243-254. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080684/
Krueger DA, Northrup H. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49:255-265. http://www.ncbi.nlm.nih.gov/pubmed/24053983
Franz DN. Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex. Biologics. 2013;7:211-221. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797614/
Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363:1801-1811. http://www.ncbi.nlm.nih.gov/pubmed/21047224
Dworakowska D, Grossman AB. Are neuroendocrine tumours a feature of tuberous sclerosis? A systemic review. Endocr Relat Cancer. 2009;16:45-58. http://www.ncbi.nlm.nih.gov/pubmed/18978035
Au KS, Ward CH, Northrup H. Tuberous sclerosis complex: disease modifiers and treatments. Curr Opin Pediatr. 2008;20:628-633. http://www.ncbi.nlm.nih.gov/pubmed/19005330
Yates JR. Tuberous sclerosis. Eur J Hum Genet. 2006;14:1065-1073. http://www.ncbi.nlm.nih.gov/pubmed/16868562
Timotin L, Sarrot-Reynauld F, Lantuejoul S, et al. Tuberous sclerosis without mental impairment, diagnosed in adulthood. Rev Med Interne. 2005;26:511-3. http://www.ncbi.nlm.nih.gov/pubmed/15936480
Curatolo P, Bombardieri R, Verdecchia M, Seri S. Intractable seizures in tuberous sclerosis complex: from molecular pathogenesis to the rationale for treatment. J Child Neurol. 2005;20:318-25. http://www.ncbi.nlm.nih.gov/pubmed/15921233
Mayer K, et al. Mutation screening of the entire coding regions of the TSC1 and the TSC2 gene with the protein truncation test (PTT) identifies frequent splicing defects. Hum Mutat. 1999;14:401-411. http://www.ncbi.nlm.nih.gov/pubmed/10533066
Kwiatkowska J, Jozwiak S, Hall F, et al. Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance. Ann Hum Genet. 1998;62:277-285. http://www.ncbi.nlm.nih.gov/pubmed/9924605
Au KS, Rodriguez JA, Finch JL, et al. Germ-line mutational analysis of the TSC2 gene in 90 tuberous-sclerosis patients. Am J Hum Genet. 1998;62:286-294. http://www.ncbi.nlm.nih.gov/pubmed/9463313
DiMario FJ Jr. Tuberous Sclerosis. Epocrates website, Last Updated: 11/28/18.. Available at: https://online.epocrates.com/diseases/67311/Tuberous-sclerosis-complex/Key-Highlights Accessed Oct 1, 2019.
Northrup H, Koenig MK, Pearson DA, et al. Tuberous Sclerosis Complex. 1999 Jul 13 [Updated 2018 Jul 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1220/ Accessed Oct 1, 2019.
Curatolo P. Tuberous Sclerosis. Orphanet Encyclopedia, October 2015. Available at: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=805 Accessed Oct 1, 2019.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/
Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/
This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/