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Pediatric Annals Apr 2017Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present at any age and can affect multiple organ systems. This disorder is usually identified in... (Review)
Review
Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present at any age and can affect multiple organ systems. This disorder is usually identified in infants and children based on characteristic skin lesions, seizures, and cellular overgrowth or hamartomas in the heart, brain, and kidneys. Tuberous sclerosis complex is a genetic disorder caused by a mutation in either the TSC1 or TSC2 gene leading to dysfunction of hamartin or tuberin, respectively. Hamartin and tuberin form a protein complex that helps regulate cellular hyperplasia. Accurate diagnosis is essential in implementing appropriate surveillance and treatment to patients with this disorder. Specific guidelines for diagnosis, surveillance, and management have been proposed by the International Tuberous Sclerosis Complex Consensus Group. Treatment of tuberous sclerosis complex is in part symptomatic; however, for certain clinical manifestations, specific treatments may be indicated. [Pediatr Ann. 2017;46(4):e166-e171.].
Topics: Child; Combined Modality Therapy; Genetic Markers; Humans; Infant; Prognosis; Tuberous Sclerosis
PubMed: 28414398
DOI: 10.3928/19382359-20170320-01 -
Anais Brasileiros de Dermatologia Jun 2018Tuberous sclerosis complex is a multisystemic, autosomal dominant genetic disorder with complete penetrance, that can evolve with hamartomas in multiple organs, such as... (Review)
Review
Tuberous sclerosis complex is a multisystemic, autosomal dominant genetic disorder with complete penetrance, that can evolve with hamartomas in multiple organs, such as skin, central nervous system, kidney and lung. Due to the wide phenotypic variability, the disease is often not recognized. Tuberous sclerosis complex affects one in 10,000 newborns and most patients are diagnosed during the first 15 months of life. The diagnostic criteria for tuberous sclerosis were reviewed in 2012, at the second International Tuberous Sclerosis Complex Consensus Conference. The diagnosis is based on genetic criteria, by the identification of inactivating pathogenic mutation of tumor suppressor genes TSC1 and TSC2, and clinical criteria, including cutaneous, renal, pulmonary, cardiac and neurological manifestations. The treatment of tuberous sclerosis complex consists, mainly, in management of the symptoms caused by hamartomas and in prevention of organ failure. Multidisciplinary approach is recommended, in order to obtain better clinical outcomes.
Topics: Hamartoma; Humans; Immunosuppressive Agents; Mutation; Sirolimus; Tuberous Sclerosis
PubMed: 29924239
DOI: 10.1590/abd1806-4841.20186972 -
Pediatric Neurology Oct 2021Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric...
BACKGROUND
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations.
METHODS
Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required.
RESULTS
Only two changes were made to clinical diagnostic criteria reported in 2013: "multiple cortical tubers and/or radial migration lines" replaced the more general term "cortical dysplasias," and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals.
CONCLUSIONS
Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.
Topics: Child; Consensus; Humans; Practice Guidelines as Topic; Tuberous Sclerosis
PubMed: 34399110
DOI: 10.1016/j.pediatrneurol.2021.07.011 -
Seminars in Pediatric Neurology Apr 2021Affecting approximately 1 per 6000-10,000 individuals, tuberous sclerosis complex (TSC) is a neurocutaneous disorder that is not only uncommon but at risk to go... (Review)
Review
Affecting approximately 1 per 6000-10,000 individuals, tuberous sclerosis complex (TSC) is a neurocutaneous disorder that is not only uncommon but at risk to go underrecognized. Similar to other phakomatoses, TSC is a disorder of cellular proliferation and migration producing hamartomas-benign tumors or malignant cancers affecting the skin and brain-and also involving the heart, kidneys, lungs and eyes in ways that can vary across the lifetime. It also occurs and varies across generations. Among medical subspecialists, the pediatric neurologist is often responsible for making the initial diagnosis when the affected individual presents with infantile spasms or another early-onset epilepsy syndrome. In recent decades, the identification of the responsible genes and gene products forming the mechanistic target of rapamycin complex, previously termed the mammalian target of rapamycin, not only has expanded our understanding of tuberous sclerosis pathophysiology, but has also inspired the search for targeted interventions.
Topics: Brain; Child; Humans; Spasms, Infantile; Tuberous Sclerosis
PubMed: 33892851
DOI: 10.1016/j.spen.2021.100875 -
Lancet (London, England) Aug 2008Tuberous sclerosis is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and... (Review)
Review
Tuberous sclerosis is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. The affected genes are TSC1 and TSC2, encoding hamartin and tuberin respectively. The hamartin-tuberin complex inhibits the mammalian-target-of-rapamycin pathway, which controls cell growth and proliferation. Variations in the distribution, number, size, and location of lesions cause the clinical syndrome to vary, even between relatives. Most features of tuberous sclerosis become evident only in childhood after 3 years of age, limiting their usefulness for early diagnosis. Identification of patients at risk for severe manifestations is crucial. Increasing understanding of the molecular abnormalities caused by tuberous sclerosis may enable improved management of this disease.
Topics: Electroencephalography; Humans; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins
PubMed: 18722871
DOI: 10.1016/S0140-6736(08)61279-9 -
Handbook of Clinical Neurology 2013Tuberous sclerosis complex (TSC) is a genetic multisystem disorder characterized by widespread hamartomas in several organs, including the brain, heart, skin, eyes,... (Review)
Review
Tuberous sclerosis complex (TSC) is a genetic multisystem disorder characterized by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. The affected genes are TSC1 and TSC2, encoding hamartin and tuberin respectively. The hamartin-tuberin complex inhibits the mammalian-target-of-Rapamycin (mTOR) pathway, which controls cell growth and proliferation. Variations in the distribution, number, size, and location of lesions cause the clinical syndrome to vary even between relatives. About 85% of children and adolescents with TSC have CNS complications, including epilepsy, cognitive impairment, challenging behavioral problems, and autism-like symptoms. Epilepsy generally begins during the first year of life, with focal seizures and spasms. The discovery of the mTOR pathway upregulation in TSC-associated lesions presents new possibilities for treatment strategy. Increasing understanding of the molecular abnormalities caused by TSC may enable improved management of the disease.
Topics: Cognition Disorders; Epilepsy; Genetic Association Studies; Humans; Tuberous Sclerosis
PubMed: 23622183
DOI: 10.1016/B978-0-444-52891-9.00038-5 -
Handbook of Clinical Neurology 2015Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect the brain, skin, eyes, kidneys, heart, and lungs. TSC alters cellular proliferation and... (Review)
Review
Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect the brain, skin, eyes, kidneys, heart, and lungs. TSC alters cellular proliferation and differentiation, resulting in hamartomas of various organs, tumor formation, and altered neuronal migration. The phenotype is highly variable. Most individuals have seizures, commonly including infantile spasms, and there is variable intellectual disability and autism. Neonates can present with cardiac failure due to intracardiac rhabdomyomas. The likelihood of renal angiomyolipomas increases with age, and renal disease is the most common cause of death in adults with TSC. Pulmonary involvement occurs predominantly in women and carries a high morbidity and mortality. TSC is inherited as an autosomal dominant trait, but spontaneous mutations are common. A mutation of either TSC1 on chromosome 9 or TSC2 on chromosome 16 leads to dysfunction of hamartin or tuberin, respectively. These two proteins form a functional complex that modulates the mammalian target of rapamycin (mTOR) pathway. Medications that inhibit mTOR are being used to treat TSC-related tumors, and current studies are investigating whether these agents could alleviate other TSC complications. Consensus statements guide identification and optimal management of many of the TSC-related complications at diagnosis and throughout the lifespan. A multidisciplinary approach is necessary for optimal management of individuals with TSC.
Topics: Brain; Female; History, 19th Century; Humans; Male; Mouth Diseases; Mutation; Skin; TOR Serine-Threonine Kinases; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins
PubMed: 26564073
DOI: 10.1016/B978-0-444-62702-5.00006-8 -
Journal of Cutaneous Medicine and... Nov 2023
Topics: Humans; Tuberous Sclerosis; Facial Neoplasms; Angiofibroma
PubMed: 37195068
DOI: 10.1177/12034754231174851 -
La Revue de Medecine Interne Oct 2021Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects different organs and caused by loss-of-function mutations in one of two genes: TSC1 or... (Review)
Review
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects different organs and caused by loss-of-function mutations in one of two genes: TSC1 or TSC2. TSC1 or TSC2 gene mutation lead to dysfunction of hamartin or tuberin, respectively. Hamartin and tuberin form a protein complex that helps regulate cellular proliferation. These proteins form a complex that constitutively inhibits the mammalian target of rapamycin (mTOR) signaling pathway, leading to permanent activation of mTOR signaling within all TSC-associated lesions. Major features of TSC include tumors of the brain, skin, heart, lungs and kidneys, seizures and TSC-associated neuropsychiatric disorders, which can include autism spectrum disorder and cognitive disability. These disorders are usually diagnosed in children and adults. Specific guidelines for diagnosis, surveillance, and management have been proposed by the International Tuberous Sclerosis Complex Consensus Group. Several randomized controlled trials led to regulatory approval of the use of mTOR inhibitors for the treatment of renal angiomyolipomas, brain subependymal giant cell astrocytomas, refractory epilepsy and pulmonary lymphangioleiomyomatosis.
Topics: Autism Spectrum Disorder; Humans; Lymphangioleiomyomatosis; Tuberous Sclerosis; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins
PubMed: 33836894
DOI: 10.1016/j.revmed.2021.03.003 -
Critical Reviews in Oncogenesis 2022Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects both fetal development and postnatal tissue growth, resulting in altered brain structures... (Review)
Review
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects both fetal development and postnatal tissue growth, resulting in altered brain structures and a tumor predisposition syndrome. Although every organ system is affected by the disease, kidney involvement is a leading cause of death in adults with TSC. Over the past decade, significant progress has been made in understanding the renal disease. This review focuses on the cystic and solid renal lesions in TSC, including their pathobiology and treatment.
Topics: Adult; Humans; Tuberous Sclerosis; Kidney Diseases
PubMed: 36734871
DOI: 10.1615/CritRevOncog.2022042857