Materiały źródłowe

• #1 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  Tuberous sclerosis complex is highly variable in clinical presentation and findings. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. […] Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). […] The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals. […] The recommendation of the Genetics Panel was to make identification of a pathogenic mutation in TSC1 or TSC2 an independent diagnostic criterion, sufficient for the diagnosis or prediction of TSC regardless of the clinical findings.

• #2 Medical Care for Tuberous Sclerosis Complex Symptoms

  https://www.massgeneral.org/neurology/tsc/patient-education/medical-care

  Because tuberous sclerosis complex (TSC) is a lifelong condition, it is important for all individuals with the disorder to be followed medically from infancy through old age. […] What is clear for all cases, however, is that early diagnosis, careful monitoring, and intervention can dramatically improve the long-term prognosis for people with TSC. […] Collaboration among specialists and the primary, or referring, physician is critical to effective diagnosis and treatment of a person with TSC. […] When physicians suspect that an individual has TSC, they typically perform the following examinations: […] If a TSC diagnosis is confirmed the following additional testing is recommended: […] Following diagnosis, a schedule for routine follow-up care should be established with the individual’s physician or team of physicians.

• #3 Diagnostic criteria – TSC Alliance

  https://www.tscalliance.org/understanding-tsc/diagnosis-criteria/

  In 2021, the International Tuberous Sclerosis Complex Consensus Group reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria published in 2013. Clinical features of TSC and genetic testing provide two ways of obtaining a diagnosis of TSC. […] The clinical and genetic diagnostic criteria of 2021 are summarized below: […] 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.

• #4 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  Tuberous sclerosis complex is highly variable in clinical presentation and findings. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. […] Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). […] The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals. […] The recommendation of the Genetics Panel was to make identification of a pathogenic mutation in TSC1 or TSC2 an independent diagnostic criterion, sufficient for the diagnosis or prediction of TSC regardless of the clinical findings.

• #5 Diagnostic criteria – TSC Alliance

  https://www.tscalliance.org/understanding-tsc/diagnosis-criteria/

  In 2021, the International Tuberous Sclerosis Complex Consensus Group reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria published in 2013. Clinical features of TSC and genetic testing provide two ways of obtaining a diagnosis of TSC. […] The clinical and genetic diagnostic criteria of 2021 are summarized below: […] 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.

• #6 Diagnostic Criteria – Tuberous Sclerosis Australia

  https://tsa.org.au/understanding-tsc/diagnostic-criteria/

  In 2021, the International Tuberous Sclerosis Complex Consensus Group reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria published in 2013. […] The clinical and genetic diagnostic criteria of 2021 are summarised below. […] A definite diagnosis of TSC (Tuberous Sclerosis Complex) will be made when an individual has either: 2 major features; OR 1 major feature with 2 minor features. […] A possible diagnosis of TSC (Tuberous Sclerosis Complex) will be made when an individual has either: 1 major feature; OR 1 major and 1 minor feature; or more than 2 minor features. […] A combination of the two major clinical features Lymphangioleiomyomatosis (LAM) and Angiomyolipomas without other features does not meet criteria for a Definite Diagnosis.

• #7 Table: International Tuberous Sclerosis Complex (TSC) Diagnostic Criteria-Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/multimedia/table/international-tuberous-sclerosis-complex-tsc-diagnostic-criteria

  International Tuberous Sclerosis Complex (TSC) Diagnostic Criteria […] A definite diagnosis of TSC requires either of the following: The identification of either a TSC1 or TSC2 pathogenic mutation by molecular genetic testing […] Two major features or 1 major feature with 2 minor features. A possible diagnosis of TSC requires the following: Either 1 major feature or 2 minor features […] A combination of the two major clinical features (lymphangioleiomyomatosis and angiomyolipomas) without other features does not meet the criteria for a definite diagnosis.

• #8 Tuberous sclerosis (diagnostic criteria) | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/tuberous-sclerosis-diagnostic-criteria-1?lang=us

  The tuberous sclerosis diagnostic criteria have been developed to aid the diagnosis of tuberous sclerosis and have been updated in 2012 by the International Tuberous Sclerosis Complex Consensus Group (at time of writing – 2019). […] The identification of either a TSC1 or TSC2 pathogenic mutation is sufficient to make a definite diagnosis of tuberous sclerosis complex. Of note, 10-25% of TSC patients have no mutation identified by conventional genetic testing, which does not exclude TSC or prevent the use of clinical diagnostic criteria to diagnose TSC. […] Definite TS complex: either 2 major features or 1 major and 2 or more minor. […] Possible TS complex: either 1 major or 2 minor. […] A combination of the two following major features (LAM and angiomyolipomas) without other feature does not meet criteria for a definite diagnosis of TSC.

• #9 Diagnostic criteria – TSC Alliance

  https://www.tscalliance.org/understanding-tsc/diagnosis-criteria/

  In 2021, the International Tuberous Sclerosis Complex Consensus Group reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria published in 2013. Clinical features of TSC and genetic testing provide two ways of obtaining a diagnosis of TSC. […] The clinical and genetic diagnostic criteria of 2021 are summarized below: […] 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.

• #10 Tuberous Sclerosis Complex Workup: Diagnostic Criteria, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/1177711-workup

  According to the 2021 diagnostic criteria from the International Tuberous Sclerosis Complex Consensus Conference, major features of TSC include the following: […] The following are the diagnostic criteria for TSC: Definite TSC – Two major features or one major feature plus two or more minor features […] Possible TSC – Either one major feature or two or more minor features […] Laboratory studies are performed as indicated clinically to identify genetic mutations associated with the disorder, monitor anticonvulsant treatment, identify idiosyncratic or dose-related adverse effects, and identify or monitor underlying renal or pulmonary disease. […] Three imaging procedures are usually undertaken in tuberous sclerosis complex (TSC): CT or MRI scans of the brain, renal ultrasounds, and echocardiograms.

• #11 Tuberous sclerosis complex — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/tuberous-sclerosis-complex/

  Diagnosis of TSC can be clinical or genetic. Updated international tuberous sclerosis complex diagnostic criteria suggest that a definite clinical diagnosis of TSC can be made in a patient with two major features of the condition, or one major feature together with two minor features. One major feature, or two or more minor features, suggests a possible clinical diagnosis of TSC. […] The major features of TSC are: hypomelanotic macules (at least three that are at least five millimetres in diameter) these are also known as ash leaf spots; a Woods light may help to visualise them; angiofibromas (at least three) or fibrous cephalic plaque; ungual fibromas (at least two); shagreen patch; multiple retinal hamartomas; cortical dysplasias, such as multiple cortical tubers and/or cerebral white matter radial migration lines; subependymal nodules (at least two); SEGA; cardiac rhabdomyoma; LAM; and angiomyolipomas (AML at least two). […] For genetic diagnosis, a pathogenic variant in TSC1 or TSC2 will also confirm TSC.

• #12 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  A significant fraction (10-25%) of TSC patients have no mutation identified by conventional genetic testing. Therefore, a normal result does not exclude TSC. […] The new, updated diagnostic clinical criteria now include 11 major features and six minor features. […] The presence of a shagreen patch was retained as a major feature, but the criterion was updated by deletion of connective tissue nevus because this term encompasses a variety of skin lesions with excessive dermal connective tissue that are not necessarily associated with TSC. […] The finding of more than one retinal hamartoma was determined to be significant and specific enough to retain as a major feature. […] Subependymal nodules and subependymal giant cell astrocytomas will continue to represent two separate major features.

• #13 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  The cardiology panel recommended retaining cardiac rhabdomyoma as a major feature and determined that there is no need to specify one versus more than one. […] The pulmonology panel recommended retaining the finding of lymphangioleiomyomatosis (LAM) as a major feature of the clinical criteria to diagnose TSC. […] The nephrology panel attending the Consensus Conference agreed with deleting the designation of renal in the major feature renal angiomyolipomas to now use angiomyolipomas (2) in the clinical diagnostic criteria.

• #14 Diagnostic Criteria – Tuberous Sclerosis Australia

  https://tsa.org.au/understanding-tsc/diagnostic-criteria/

  In 2021, the International Tuberous Sclerosis Complex Consensus Group reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria published in 2013. […] The clinical and genetic diagnostic criteria of 2021 are summarised below. […] A definite diagnosis of TSC (Tuberous Sclerosis Complex) will be made when an individual has either: 2 major features; OR 1 major feature with 2 minor features. […] A possible diagnosis of TSC (Tuberous Sclerosis Complex) will be made when an individual has either: 1 major feature; OR 1 major and 1 minor feature; or more than 2 minor features. […] A combination of the two major clinical features Lymphangioleiomyomatosis (LAM) and Angiomyolipomas without other features does not meet criteria for a Definite Diagnosis.

• #15 How TSC is Diagnosed

  https://www.massgeneral.org/neurology/tsc/patient-education/diagnosis

  To diagnose TSC with certainty, physicians rely on a constellation of features, rather than any single manifestation. […] Tuberous sclerosis complex (TSC) is often difficult to diagnose. […] To make distinctions about the significance of features and to reach a clinical diagnosis, physicians rely on very specific diagnostic criteria, first developed in 1979 and revised most recently in 1998. […] The diagnostic criteria for TSC distinguish between major features and minor features of the disorder. […] In light of these criteria, diagnosis of an individual suspected of having TSC is based on a careful physical examination, during which a physician examines the skin for various TSC-related abnormalities, as well as the fingernails and toenails for periungual fibromas, and the teeth and gums for dental pits and/or gingival fibromas. […] Based on their clinical findings, physicians use the diagnostic criteria to determine the level of certainty of a diagnosis. […] In addition to physical and imaging examinations, individuals suspected of having TSC typically undergo genetic testing.

• #16 Tuberous sclerosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tuberous-sclerosis/diagnosis-treatment/drc-20365971

  Depending on symptoms, you or your child may see several different specialists who are experts in tuberous sclerosis. […] The health care provider usually does a physical exam and talks with you about symptoms and family history. The provider looks for growths, also called noncancerous tumors, that are commonly caused by tuberous sclerosis. The provider also will likely order several tests including blood tests and genetic tests to diagnose tuberous sclerosis and identify related problems. […] Genetic testing can confirm the diagnosis of tuberous sclerosis. If a child is diagnosed with tuberous sclerosis without a family history of the condition, both parents may want to consider genetic testing for tuberous sclerosis for themselves. Genetic counseling can help parents understand the risk of tuberous sclerosis for their other children and any future children. […] A health care provider who sees your child for possible tuberous sclerosis will ask you several questions. Be ready to answer them so you have time to discuss whatever is most important to you.

• #17 How TSC is Diagnosed

  https://www.massgeneral.org/neurology/tsc/patient-education/diagnosis

  To diagnose TSC with certainty, physicians rely on a constellation of features, rather than any single manifestation. […] Tuberous sclerosis complex (TSC) is often difficult to diagnose. […] To make distinctions about the significance of features and to reach a clinical diagnosis, physicians rely on very specific diagnostic criteria, first developed in 1979 and revised most recently in 1998. […] The diagnostic criteria for TSC distinguish between major features and minor features of the disorder. […] In light of these criteria, diagnosis of an individual suspected of having TSC is based on a careful physical examination, during which a physician examines the skin for various TSC-related abnormalities, as well as the fingernails and toenails for periungual fibromas, and the teeth and gums for dental pits and/or gingival fibromas. […] Based on their clinical findings, physicians use the diagnostic criteria to determine the level of certainty of a diagnosis. […] In addition to physical and imaging examinations, individuals suspected of having TSC typically undergo genetic testing.

• #18 Diagnosis – The Tuberous Sclerosis Association

  https://tuberous-sclerosis.org/information-and-support/diagnosis/

  The age, time and background of a Tuberous Sclerosis Complex (TSC) diagnosis can vary dramatically between everyone living with the condition. However, the signs, symptoms and methods used to confirm a TSC diagnosis can be very similar. […] Usually, a diagnosis of TSC follows a result of careful physical examinations in combination with scans and imaging procedures, such as an MRI scan. […] Clinicians may also use a checklist of characteristic features of TSC – such as abnormal areas of skin, or tumours in your eyes, brain, heart, lungs or kidneys – to confirm a diagnosis. Several tests will be needed to check for these features. […] It is possible to perform genetic testing to help identify TSC. This often takes place when TSC is suspected in an individual, with their immediate family often also tested. Genetic testing is correct in around 80% of cases.

• #19 Tuberous sclerosis complex — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/tuberous-sclerosis-complex/

  Diagnosis of TSC can be clinical or genetic. Updated international tuberous sclerosis complex diagnostic criteria suggest that a definite clinical diagnosis of TSC can be made in a patient with two major features of the condition, or one major feature together with two minor features. One major feature, or two or more minor features, suggests a possible clinical diagnosis of TSC. […] The major features of TSC are: hypomelanotic macules (at least three that are at least five millimetres in diameter) these are also known as ash leaf spots; a Woods light may help to visualise them; angiofibromas (at least three) or fibrous cephalic plaque; ungual fibromas (at least two); shagreen patch; multiple retinal hamartomas; cortical dysplasias, such as multiple cortical tubers and/or cerebral white matter radial migration lines; subependymal nodules (at least two); SEGA; cardiac rhabdomyoma; LAM; and angiomyolipomas (AML at least two). […] For genetic diagnosis, a pathogenic variant in TSC1 or TSC2 will also confirm TSC.

• #20 Tuberous Sclerosis: Symptoms, Diagnosis & Treatments

  https://www.healthline.com/health/tuberous-sclerosis

  Tuberous sclerosis (TS) can be diagnosed by genetic testing or a series of tests that includes an MRI of the brain, a CT scan of the head, an electrocardiogram, an echocardiogram, a kidney ultrasound, an eye exam, and looking at your skin under a Woods lamp, which emits ultraviolet light. […] A diagnosis of TS can be confirmed with genetic tests. When considering genetic testing for family planning, it’s important to remember that only one-third of TS cases are inherited. If you have a family history of TS, it’s possible to get genetic testing to see if you carry the gene. […] TS is diagnosed by genetic testing or a series of tests that includes: an MRI of the brain, a CT scan of the head, an electrocardiogram, an echocardiogram, a kidney ultrasound, an eye exam, looking at your skin under a Woods lamp, which emits ultraviolet light. […] A precise diagnosis will require a CT scan and an MRI along with a full clinical exam.

• #21 Tuberous Sclerosis Complex | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/tuberous-sclerosis-complex

  Diagnosing TSC is based upon a review of the signs and symptoms, the persons family history, and diagnostic testing. The tests used to diagnose TSC include CT (computed tomography) or MRI (magnetic resonance imaging), ultrasound, and electrocardiogram (EKG). Seizures and delayed development may be the first signs of TSC. A careful examination of the skin, nails, teeth, gums, and eyes for characteristic features of TSC also can help diagnose the disorder. […] Genetic testing can help parents determine if they are carriers of one of the genes that cause TSC. A genetic counselor can provide information about the test and what the results could mean.

• #22 Tuberous Sclerosis Complex Workup: Diagnostic Criteria, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/1177711-workup

  According to the 2021 diagnostic criteria from the International Tuberous Sclerosis Complex Consensus Conference, major features of TSC include the following: […] The following are the diagnostic criteria for TSC: Definite TSC – Two major features or one major feature plus two or more minor features […] Possible TSC – Either one major feature or two or more minor features […] Laboratory studies are performed as indicated clinically to identify genetic mutations associated with the disorder, monitor anticonvulsant treatment, identify idiosyncratic or dose-related adverse effects, and identify or monitor underlying renal or pulmonary disease. […] Three imaging procedures are usually undertaken in tuberous sclerosis complex (TSC): CT or MRI scans of the brain, renal ultrasounds, and echocardiograms.

• #23

  https://www.nhs.uk/conditions/tuberous-sclerosis/diagnosis/

  To diagnose tuberous sclerosis, you’ll be asked about your family’s medical history. You’ll also have a number of tests to look for signs of the condition. […] Healthcare professionals use a checklist of the characteristic features of tuberous sclerosis such as abnormal areas of skin, or tumours in your eyes, brain, heart, lungs or kidneys to confirm a diagnosis. Several tests will be needed to check for these features. […] Tests you may have to check for tuberous sclerosis include: an eye examination to check for eye tumours, a skin examination to look for abnormal growths or patches of pale or thickened skin, an MRI scan to detect tumours in the brain or kidneys, a CT scan or ultrasound scan to detect tumours in the kidneys, heart or lungs, an electroencephalogram (EEG) to detect abnormal electrical activity within the brain associated with epilepsy, an electrocardiogram (ECG) to detect abnormal electrical activity in the heart that could be caused by heart tumours. […] A genetic blood test to look for the faulty genes that cause tuberous sclerosis can also help make a diagnosis, although it isn’t always reliable.

• #24 Tuberous Sclerosis Complex: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1177711-overview

  Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder affecting cellular differentiation, proliferation, and migration early in development, resulting in a variety of hamartomatous lesions that may affect virtually every organ system of the body. […] Diagnosis should be possible in most cases using established clinical criteria. Molecular genetic testing is useful in uncertain or questionable cases, as well as for prenatal diagnosis and for screening family members of an affected individual. […] The following three imaging studies are usually undertaken in patients with TSC: Computed tomography scanning or magnetic resonance imaging of the brain: Performed to identify SEGAs before obstructive hydrocephalus occurs; they also identify the extent and number of cortical tubers present.

• #25 Tuberous Sclerosis Complex: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1177711-overview

  Renal ultrasonography: Performed to assess change in AMLs or cysts, in the hope that this will allow operative intervention prior to the development of renal failure. […] Echocardiography: Performed as part of the baseline evaluation in a patient with newly diagnosed or suspected TSC. […] Electroencephalography: Should be performed in patients with TSC in whom seizures are suspected; follow-up electroencephalography is performed as clinically indicated. […] Baseline electrocardiography is recommended for all patients newly diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their presenting symptom.

• #26

  https://www.nhs.uk/conditions/tuberous-sclerosis/diagnosis/

  To diagnose tuberous sclerosis, you’ll be asked about your family’s medical history. You’ll also have a number of tests to look for signs of the condition. […] Healthcare professionals use a checklist of the characteristic features of tuberous sclerosis such as abnormal areas of skin, or tumours in your eyes, brain, heart, lungs or kidneys to confirm a diagnosis. Several tests will be needed to check for these features. […] Tests you may have to check for tuberous sclerosis include: an eye examination to check for eye tumours, a skin examination to look for abnormal growths or patches of pale or thickened skin, an MRI scan to detect tumours in the brain or kidneys, a CT scan or ultrasound scan to detect tumours in the kidneys, heart or lungs, an electroencephalogram (EEG) to detect abnormal electrical activity within the brain associated with epilepsy, an electrocardiogram (ECG) to detect abnormal electrical activity in the heart that could be caused by heart tumours. […] A genetic blood test to look for the faulty genes that cause tuberous sclerosis can also help make a diagnosis, although it isn’t always reliable.

• #27 Tuberous Sclerosis Complex Workup: Diagnostic Criteria, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/1177711-workup

  Under optimal circumstances, molecular genetic testing identifies mutations in up to 75-80% of individuals with tuberous sclerosis complex (TSC). Therefore, a negative genetic diagnostic test result does not exclude a diagnosis of TSC. […] EEG should be performed in patients with tuberous sclerosis complex (TSC) in whom seizures are suspected. […] Baseline ECG is recommended for all patients newly diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their presenting symptom.

• #28 Tuberous Sclerosis Complex Workup: Diagnostic Criteria, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/1177711-workup

  Under optimal circumstances, molecular genetic testing identifies mutations in up to 75-80% of individuals with tuberous sclerosis complex (TSC). Therefore, a negative genetic diagnostic test result does not exclude a diagnosis of TSC. […] EEG should be performed in patients with tuberous sclerosis complex (TSC) in whom seizures are suspected. […] Baseline ECG is recommended for all patients newly diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their presenting symptom.

• #29 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  Tuberous sclerosis complex is highly variable in clinical presentation and findings. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. […] Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). […] The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals. […] The recommendation of the Genetics Panel was to make identification of a pathogenic mutation in TSC1 or TSC2 an independent diagnostic criterion, sufficient for the diagnosis or prediction of TSC regardless of the clinical findings.

• #30 Tuberous sclerosis (diagnostic criteria) | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/tuberous-sclerosis-diagnostic-criteria-1?lang=us

  The tuberous sclerosis diagnostic criteria have been developed to aid the diagnosis of tuberous sclerosis and have been updated in 2012 by the International Tuberous Sclerosis Complex Consensus Group (at time of writing – 2019). […] The identification of either a TSC1 or TSC2 pathogenic mutation is sufficient to make a definite diagnosis of tuberous sclerosis complex. Of note, 10-25% of TSC patients have no mutation identified by conventional genetic testing, which does not exclude TSC or prevent the use of clinical diagnostic criteria to diagnose TSC. […] Definite TS complex: either 2 major features or 1 major and 2 or more minor. […] Possible TS complex: either 1 major or 2 minor. […] A combination of the two following major features (LAM and angiomyolipomas) without other feature does not meet criteria for a definite diagnosis of TSC.

• #31 Tuberous Sclerosis Complex Workup: Diagnostic Criteria, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/1177711-workup

  Under optimal circumstances, molecular genetic testing identifies mutations in up to 75-80% of individuals with tuberous sclerosis complex (TSC). Therefore, a negative genetic diagnostic test result does not exclude a diagnosis of TSC. […] EEG should be performed in patients with tuberous sclerosis complex (TSC) in whom seizures are suspected. […] Baseline ECG is recommended for all patients newly diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their presenting symptom.

• #32 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  A significant fraction (10-25%) of TSC patients have no mutation identified by conventional genetic testing. Therefore, a normal result does not exclude TSC. […] The new, updated diagnostic clinical criteria now include 11 major features and six minor features. […] The presence of a shagreen patch was retained as a major feature, but the criterion was updated by deletion of connective tissue nevus because this term encompasses a variety of skin lesions with excessive dermal connective tissue that are not necessarily associated with TSC. […] The finding of more than one retinal hamartoma was determined to be significant and specific enough to retain as a major feature. […] Subependymal nodules and subependymal giant cell astrocytomas will continue to represent two separate major features.

• #33 Diagnostic Criteria – Tuberous Sclerosis Australia

  https://tsa.org.au/understanding-tsc/diagnostic-criteria/

  Either a TSC1 or TSC2 pathogenic mutation is sufficient to make a Definite Diagnosis of TSC. A pathogenic mutation is defined as a sequence variant that clearly prevents TSC1 or TSC2 protein production. Additionally, some mutations compatible with protein production are well established as disease-causing and as sufficient to make a Definite Diagnosis of TSC. Other variants should be considered with caution.

• #34 Tuberous sclerosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tuberous-sclerosis/diagnosis-treatment/drc-20365971

  Depending on symptoms, you or your child may see several different specialists who are experts in tuberous sclerosis. […] The health care provider usually does a physical exam and talks with you about symptoms and family history. The provider looks for growths, also called noncancerous tumors, that are commonly caused by tuberous sclerosis. The provider also will likely order several tests including blood tests and genetic tests to diagnose tuberous sclerosis and identify related problems. […] Genetic testing can confirm the diagnosis of tuberous sclerosis. If a child is diagnosed with tuberous sclerosis without a family history of the condition, both parents may want to consider genetic testing for tuberous sclerosis for themselves. Genetic counseling can help parents understand the risk of tuberous sclerosis for their other children and any future children. […] A health care provider who sees your child for possible tuberous sclerosis will ask you several questions. Be ready to answer them so you have time to discuss whatever is most important to you.

• #35 Tuberous Sclerosis Complex | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/tuberous-sclerosis-complex

  Diagnosing TSC is based upon a review of the signs and symptoms, the persons family history, and diagnostic testing. The tests used to diagnose TSC include CT (computed tomography) or MRI (magnetic resonance imaging), ultrasound, and electrocardiogram (EKG). Seizures and delayed development may be the first signs of TSC. A careful examination of the skin, nails, teeth, gums, and eyes for characteristic features of TSC also can help diagnose the disorder. […] Genetic testing can help parents determine if they are carriers of one of the genes that cause TSC. A genetic counselor can provide information about the test and what the results could mean.

• #36 Tuberous Sclerosis (TSC) | Symptoms, Diagnosis & Treatment

  https://www.cincinnatichildrens.org/health/t/tuberous-sclerosis

  Tuberous sclerosis is often diagnosed within the first year of life but may take years if symptoms are mild. […] Diagnosing tuberous sclerosis can be a complex process because the condition impacts many of the body’s systems. At first, symptoms may be considered isolated problems when in reality they are caused by a single condition. […] In many cases, tuberous sclerosis is ultimately diagnosed by a geneticist who is trained to identify very specific gene mutations tied to the condition. However, not all instances of tuberous sclerosis can be confirmed genetically.

• #37 Tuberous sclerosis – Wikipedia

  https://en.wikipedia.org/wiki/Tuberous_sclerosis

  TSC can be first diagnosed at any stage of life. Prenatal diagnosis is possible by chance if heart tumours are discovered during routine ultrasound. In infancy, epilepsy, particularly infantile spasms, or developmental delay may lead to neurological tests. The white patches on the skin may also first become noticed. In childhood, behavioural problems and autism spectrum disorder may provoke a diagnosis. During adolescence, the skin problems appear. In adulthood, kidney and lung problems may develop. An individual may also be diagnosed at any time as a result of genetic testing of family members of another affected person.

• #38 Early Diagnosis of Tuberous Sclerosis Complex: Prenatal Diagnosis | American Journal of Neuroradiology

  https://www.ajnr.org/content/early/2023/08/03/ajnr.A7952

  Strong emphasis has been placed recently on early (4 postnatal months) detection of tuberous sclerosis complex and the introduction of antiepileptic treatment before seizure onset. […] This objective can be achieved prenatally: Cardiac rhabdomyomas and the major diagnostic tuberous sclerosis complex sign are detected during fetal ultrasound, and prenatal MR imaging allows detection of cerebral major manifestations: cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas. […] In the remaining 39 fetuses (78%), MR imaging revealed a prenatal diagnosis of tuberous sclerosis complex, having shown an additional 13 major criteria: subependymal nodules in all cases (39/39=100.0%), subependymal giant cell astrocytomas in 6 (6/39=15.4%), and cortical tubers in 24 (24/39=61.5%).

• #39 Early Diagnosis of Tuberous Sclerosis Complex: Prenatal Diagnosis | American Journal of Neuroradiology

  https://www.ajnr.org/content/early/2023/08/03/ajnr.A7952

  A schedule of proper care of children with tuberous sclerosis complex can be established during the perinatal period due to education of women to report for mandatory ultrasound examinations during pregnancy, the good quality of ultrasound, and referral to MR imaging if a cardiac tumor is depicted on ultrasound. […] Gynecologists and pediatric cardiologists performing fetal ultrasound and radiologists performing prenatal MR imaging are a key to early diagnosis of tuberous sclerosis complex in many cases. […] Two major features are sufficient to make a definite diagnosis of TSC, and 2 diagnostic methods (fetal US and MR imaging) are necessary to reach this diagnosis, also before birth. […] In our material, all pregnant women with cardiac tumors diagnosed on US were referred to MR imaging. Major features of cerebral TSC were found in as many as 78% of the analyzed cases, confirming the diagnosis.

• #40 Diagnosis of tuberous sclerosis in the prenatal period: a retrospective study of 240 cases and review of the literature | European Journal of Human Genetics

  https://www.nature.com/articles/s41431-024-01631-w

  Tuberous sclerosis complex (TSC) is a rare multisystemic disorder caused by a pathogenic variant in the TSC1 or TSC2 gene. […] We report the largest series of prenatal genetic tests for TSC with a retrospective study of 240 foetuses presenting with suggestive antenatal signs. […] In this series, a definite diagnosis was assessed in 50% (41/82) of foetuses who initially presented with a single CR and 80.3% (127/158) in cases of multiple CRs. […] We also provide a review of the literature to specify the probability of clinical or genetic diagnosis of TSC in case of detection of single or multiple CRs.

• #41 Tuberous Sclerosis Complex (TSC) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/tuberous-sclerosis-complex-tsc

  Tuberous sclerosis complex (TSC) can cause a wide variety of symptoms. Many of them, such as seizures and developmental delays, are common in children who do not have TSC. Therefore, in order to diagnose the condition, doctors look for a group of symptoms. Some of the symptoms are present at birth, such as tumors on the heart and white patches on the skin. […] Your child’s medical team may run a number of different tests to diagnose TSC, including: Magnetic resonance imaging (MRI) of the brain to look for tumors in the brain and renal system that often occur in children with TSC, Echocardiogram (an ultrasound of the heart) to look for tumors on the heart, Ultrasound to identify any kidney lesions, Genetic testing to look for a TSC-related gene change. About 20 percent of people who have TSC do not have an identifiable gene change. Therefore a negative genetic test result cannot rule out a child having the condition. […] Sometimes heart tumors are seen during a routine prenatal ultrasound. These heart tumors can be an early sign of TSC. If your clinician sees this type of tumor, he or she may refer you for advanced ultrasound screening.

• #42 The Fetal Medicine Foundation

  https://fetalmedicine.org/education/fetal-abnormalities/brain/tuberous-sclerosis

  Tuberous sclerosis is found in 50% of cases of rabdomyoma (in the other 50% of cases the cardiac tumor is an isolated finding). When there are multiple rabdomyomas the risk of tuberous sclerosis is 90%. […] Detailed ultrasound examination, including neurosonography. […] Search for the mutations in the TSC1 and TSC2 genes. […] Fetal brain MRI may be useful if other brain abnormalities are suspected. […] Ultrasound scans every 4 weeks to monitor the evolution of cardiac tumors and development of arrhythmias and hydrops. […] Prognosis depends on the number, size and location of the tumors.

• #43 Diagnosis & Treatment – Tuberous Sclerosis Complex | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/neurology-and-neurosurgery/tuberous-sclerosis/treatments-and-procedures

  TSC is often detected at or before birth by the presence of heart lesions (rhabdomyomas) seen on ultrasound, which may signal the need for further evaluation. […] In infants, TSC may be suspected if the child has cardiac rhabdomyomas at birth or seizures (especially the kind called infantile spasms) in the first six months of life. With a careful examination of the skin and brain, it may be possible to diagnose TSC in a very young infant. However, many children are not diagnosed until later in life when their seizures begin or other symptoms such as facial angiofibromas appear. […] Diagnosis of TSC is based on a careful clinical exam in combination with imaging of the brain, such as computed tomography (CT) or magnetic resonance imaging (MRI) which may show tubers in the brain, and an ultrasound of the heart, liver, and kidneys, which may show tumors in those organs.

• #44 Tuberous Sclerosis Complex: Early Diagnosis in Infants | Pediatric Neurology Briefs

  https://pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-32-12

  Investigators from the Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research conducted two concurrent prospective longitudinal studies to analyze the timing and pattern of clinical presenting symptoms of TSC in infants to facilitate earlier diagnosis and treatment in this specific population. […] There were 130 participants that met diagnostic criteria for TSC. Common initial presenting symptoms were cardiac rhabdomyomas (59%) and hypomelanotic macules (39%), and 85% of the children had either or both. TSC symptoms which led to diagnosis were hypomelanotic macules (94%), tubers and other cortical dysplasias (94%), subpendymal nodules (SENs) (90%), and cardiac rhabdomyomas (82%). […] Thirty-five percent presented before birth, 41% presented at birth or within the first month of life, and 74% were diagnosed within 30 days of presentation.

• #45 Tuberous Sclerosis (TSC): Symptoms, Causes & Treatment – UChicago Medicine

  https://www.uchicagomedicine.org/conditions-services/neurology-neurosurgery/tuberous-sclerosis

  Tuberous sclerosis is often diagnosed during infancy. However, in some people with mild forms of TSC, it can remain undiagnosed. […] Because TSC can be difficult to diagnose, it is important to go to specialists who understand the signs of TSC. Early diagnosis can help prevent some complications of TSC. […] Our neurologists use a variety of tools to diagnose this complex condition, including: […] Genetic testing to check for the TSC1 and TSC2 genetic mutations. (Genetic counseling also can determine if tuberous sclerosis affects other members of your family.)

• #46 Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0764-z

  Tuberous sclerosis complex (TSC) is a genetic disorder with an incidence of 1:6000 live births and associated with the development of benign tumors in several organs. […] The aim of this study was to define the most useful approach to make the diagnosis of TSC before seizure onset (before age 4th months), in order to start early EEG monitoring with possible preventative treatment intervention. […] Early diagnosis of TSC, before seizure onset, is feasible and it is becoming pivotal for epilepsy management and improvement of cognitive outcome. Early TSC diagnosis is mostly based on clinical signs. Brain MRI, echocardiography, skin examination and genetic testing should be performed early in every patient suspected of having TSC. […] In the light of the recent studies and recommendations, it is therefore essential to make a diagnosis of TSC as soon as possible, in order to allow epileptogenic treatment before seizure onset, with a view to improvement of clinical outcome.

• #47 Tuberous Sclerosis Complex: Early Diagnosis in Infants | Pediatric Neurology Briefs

  https://pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-32-12

  The mean postnatal diagnosis was 72 days (median 32 days). […] Although seizures are not part of diagnostic criteria for TSC, epilepsy prevalence in TSC has been reported as high as 90%. […] The overall epilepsy frequency was 76% (57% infantile spasms, 55% focal seizures, and 12% other seizure types). […] Earlier seizure onset and higher seizure frequency were associated with worse developmental outcomes. […] This paper provides important information regarding how to improve early diagnosis of TSC, given that earlier identification and treatment improves developmental outcome. […] Prenatal ultrasound, neuroimaging, skin examination, and genetic testing are all essential components of this evaluation. […] The importance of earlier diagnosis is related to the high frequency of epilepsy in this population, and early treatment of seizures is essential. […] Early referral for epilepsy surgery may be effective in improving seizure control and improving developmental outcome, and should be considered early for any patient with DRE, including those with TSC.

• #48 Tuberous sclerosis – Wikipedia

  https://en.wikipedia.org/wiki/Tuberous_sclerosis

  TSC can be first diagnosed at any stage of life. Prenatal diagnosis is possible by chance if heart tumours are discovered during routine ultrasound. In infancy, epilepsy, particularly infantile spasms, or developmental delay may lead to neurological tests. The white patches on the skin may also first become noticed. In childhood, behavioural problems and autism spectrum disorder may provoke a diagnosis. During adolescence, the skin problems appear. In adulthood, kidney and lung problems may develop. An individual may also be diagnosed at any time as a result of genetic testing of family members of another affected person.

• #49 Tuberous Sclerosis (TSC) | Symptoms, Diagnosis & Treatment

  https://www.cincinnatichildrens.org/health/t/tuberous-sclerosis

  Tuberous sclerosis is often diagnosed within the first year of life but may take years if symptoms are mild. […] Diagnosing tuberous sclerosis can be a complex process because the condition impacts many of the body’s systems. At first, symptoms may be considered isolated problems when in reality they are caused by a single condition. […] In many cases, tuberous sclerosis is ultimately diagnosed by a geneticist who is trained to identify very specific gene mutations tied to the condition. However, not all instances of tuberous sclerosis can be confirmed genetically.

• #50 Diagnosis of Tuberous Sclerosis Complex

  https://www.neurologylive.com/view/diagnosis-of-tuberous-sclerosis-complex

  The other thing that’s interesting about TS [tuberous sclerosis] is when people get diagnosed. What leads to the diagnosis? As a pediatric person, I think it’s often prenatally with the cardiac rhabdomyomas or in infancy with the onset of seizures. […] A common presentation, for example, is a parent who comes in with a child with known tuberous sclerosis. We have the conversation that this is a genetic disease. Then I say, Would you like me to look at your skin or do an exam? It turns out they have some of the major or minor diagnostic features of TSC [tuberous sclerosis complex], and I say, You may have this as well, which is always a fairly sobering conversation. […] I’ve had individuals who have come in with a first-time seizure, gotten a brain MRI, and have found abnormalities in the brain that are highly consistent with TSC. Then I do a skin exam or look at the kidneys, and I’m able to assemble a diagnosis.

• #51 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Tuberous-Sclerosis-Diagnosis.aspx

  Tuberous sclerosis is a broad condition involving benign tumors that may present in various parts of the body. As a result, the symptoms of this condition can vary greatly, thus making it difficult to make an accurate diagnosis. […] The first notable sign of tuberous sclerosis for many individuals affected by the condition is seizures caused by tumors in the brain. However, some people are diagnosed after noting delayed development or abnormalities of the skin. […] Tumors in the brain that cause seizures are often the first sign noticed by individuals with tuberous sclerosis. Various types of seizures may occur, including infantile spasms that occur in young children. […] A developmental delay resulting from tumors in the brain may also be a presenting sign of someone with the condition. This varies significantly in severity, from mild aggression to attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and self-harming tendencies.

• #52 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Tuberous-Sclerosis-Diagnosis.aspx

  Cysts in the kidneys, which may affect renal function, can also be indicative of tuberous sclerosis, and usually present in individuals between the ages of 15 to 30 years old. Given the late presentation of this symptom, most individuals who experience this have already been diagnosed. […] White patches on the retina of the eyes are a diagnostic indicator of the presence of benign tumors in the eyes called phakomas. […] When an individual presents with signs that could be indicative of tuberous sclerosis, a thorough medical history should be taken, as well as a family history of relevant conditions. […] The possibility of familial disease supports the need to inquire about the patient’s family history of the disease during diagnosis. However, the mutation can also occur spontaneously without a family history of tuberous sclerosis.

• #53 Diagnosis of Tuberous Sclerosis Complex

  https://www.neurologylive.com/view/diagnosis-of-tuberous-sclerosis-complex

  The other thing that’s interesting about TS [tuberous sclerosis] is when people get diagnosed. What leads to the diagnosis? As a pediatric person, I think it’s often prenatally with the cardiac rhabdomyomas or in infancy with the onset of seizures. […] A common presentation, for example, is a parent who comes in with a child with known tuberous sclerosis. We have the conversation that this is a genetic disease. Then I say, Would you like me to look at your skin or do an exam? It turns out they have some of the major or minor diagnostic features of TSC [tuberous sclerosis complex], and I say, You may have this as well, which is always a fairly sobering conversation. […] I’ve had individuals who have come in with a first-time seizure, gotten a brain MRI, and have found abnormalities in the brain that are highly consistent with TSC. Then I do a skin exam or look at the kidneys, and I’m able to assemble a diagnosis.

• #54 Diagnosis of Tuberous Sclerosis Complex

  https://www.neurologylive.com/view/diagnosis-of-tuberous-sclerosis-complex

  It’s curious that many of them, when queried about TAND [TSC-associated neuropsychiatric disorders], report that they have a lot of the things that are very compatible with TAND. […] It’s amazing. I’ve also seen many people as adults who are diagnosed who had been living with this disorder for decades and never knew.

• #55 Tuberous Sclerosis (TSC) | Symptoms, Diagnosis & Treatment

  https://www.cincinnatichildrens.org/health/t/tuberous-sclerosis

  Tuberous sclerosis is often diagnosed within the first year of life but may take years if symptoms are mild. […] Diagnosing tuberous sclerosis can be a complex process because the condition impacts many of the body’s systems. At first, symptoms may be considered isolated problems when in reality they are caused by a single condition. […] In many cases, tuberous sclerosis is ultimately diagnosed by a geneticist who is trained to identify very specific gene mutations tied to the condition. However, not all instances of tuberous sclerosis can be confirmed genetically.

• #56 How TSC is Diagnosed

  https://www.massgeneral.org/neurology/tsc/patient-education/diagnosis

  To diagnose TSC with certainty, physicians rely on a constellation of features, rather than any single manifestation. […] Tuberous sclerosis complex (TSC) is often difficult to diagnose. […] To make distinctions about the significance of features and to reach a clinical diagnosis, physicians rely on very specific diagnostic criteria, first developed in 1979 and revised most recently in 1998. […] The diagnostic criteria for TSC distinguish between major features and minor features of the disorder. […] In light of these criteria, diagnosis of an individual suspected of having TSC is based on a careful physical examination, during which a physician examines the skin for various TSC-related abnormalities, as well as the fingernails and toenails for periungual fibromas, and the teeth and gums for dental pits and/or gingival fibromas. […] Based on their clinical findings, physicians use the diagnostic criteria to determine the level of certainty of a diagnosis. […] In addition to physical and imaging examinations, individuals suspected of having TSC typically undergo genetic testing.

• #57 Diagnosis of Tuberous Sclerosislogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/jd201102180000004/2011/02/18/diagnosis-tuberous-sclerosis

  Diagnosis of Tuberous Sclerosis […] Almost 40% of children whose cases were reviewed had signs and symptoms that could have led to earlier diagnosis. […] Diagnosis is made clinically, based on the presence of two major features or one major plus two minor features, and it can be difficult, as no sign or symptom is universal or pathognomonic, and features may emerge over time. […] Average age at diagnosis was 7.5 years (median, 1 year); 81% were diagnosed before age 10. […] Thirty-nine percent of patients had symptoms or signs of TSC that had initially been missed: most commonly, seizures (including infantile spasms) and dermatologic features (e.g., hypopigmented macules, shagreen patch, periungual fibromas, facial angiofibromas); many patients had more than one feature that had been missed.

• #58 Diagnosis of Tuberous Sclerosislogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/jd201102180000004/2011/02/18/diagnosis-tuberous-sclerosis

  The authors note that TSC2 mutations were associated with more severe phenotype. […] They emphasize that early diagnosis is important because TSC patients have an 84% lifetime risk for seizures, as well as other medical issues. […] This review demonstrates the variable presentation of TSC and highlights the importance of appropriate multidisciplinary evaluation and longitudinal follow-up to minimize missed diagnoses.

• #59 Diagnosis of Tuberous Sclerosislogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/jd201102180000004/2011/02/18/diagnosis-tuberous-sclerosis

  Diagnosis of Tuberous Sclerosis […] Almost 40% of children whose cases were reviewed had signs and symptoms that could have led to earlier diagnosis. […] Diagnosis is made clinically, based on the presence of two major features or one major plus two minor features, and it can be difficult, as no sign or symptom is universal or pathognomonic, and features may emerge over time. […] Average age at diagnosis was 7.5 years (median, 1 year); 81% were diagnosed before age 10. […] Thirty-nine percent of patients had symptoms or signs of TSC that had initially been missed: most commonly, seizures (including infantile spasms) and dermatologic features (e.g., hypopigmented macules, shagreen patch, periungual fibromas, facial angiofibromas); many patients had more than one feature that had been missed.

• #60 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Identifying the clinical pattern and, when possible, a pathogenic gene variant can give a clear diagnosis for an often difficult-to-manage set of symptoms, which has been shown in other epilepsy syndromes and neurodegenerative diseases to be helpful to patients, families, and care partners. Importantly, arriving at a clear diagnosis as early as possible can also guide treatments and provide prognostic information. […] Clinical recognition of TSC is strong enough that genetic testing is often confirmatory only. Typically, diagnosis is made with imaging studies of the brain, heart, and eyes and dermatologic evaluation after a child presents with infantile spasms, although as noted, prenatal detection of cardiac rhabdomyomas may also lead to diagnosis. Family history should be taken and skin examination and neuroimaging done for any child with infantile spasms because these may be key in making a diagnosis of TSC and guiding surveillance of other body systems. Early diagnosis has become more paramount as treatments targeting the mTOR pathway have become available. Diagnostic criteria are provided in Table 2. […] Because of the multisystem nature of TSC and the lifelong course with new symptoms appearing over time, surveillance monitoring is essential. Recommendations for monitoring are provided in Table 3.

• #61 Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0764-z

  Tuberous sclerosis complex (TSC) is a genetic disorder with an incidence of 1:6000 live births and associated with the development of benign tumors in several organs. […] The aim of this study was to define the most useful approach to make the diagnosis of TSC before seizure onset (before age 4th months), in order to start early EEG monitoring with possible preventative treatment intervention. […] Early diagnosis of TSC, before seizure onset, is feasible and it is becoming pivotal for epilepsy management and improvement of cognitive outcome. Early TSC diagnosis is mostly based on clinical signs. Brain MRI, echocardiography, skin examination and genetic testing should be performed early in every patient suspected of having TSC. […] In the light of the recent studies and recommendations, it is therefore essential to make a diagnosis of TSC as soon as possible, in order to allow epileptogenic treatment before seizure onset, with a view to improvement of clinical outcome.

• #62 Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0870-y

  This prospective surveillance study demonstrates a low age at first diagnosis (median: 6 months), likely due to antenatal detection of cardiac rhabdomyoma. Early diagnosis bears the potential for implementing effective therapies at an earlier stage. […] For classification of patients with a definite or possible diagnosis of TSC, we used the current Tuberous Sclerosis Consensus Conference updated diagnostic guidelines. […] The most common diagnostic study performed was echocardiography in 90.7% (78/86), followed by ultrasound (cerebral or abdominal) in 89.5% (77/86). An electroencephalogram (EEG) was performed in 84.9% (73/86) of cases. […] We here present a prospective epidemiological study that aimed at determining the incidence of TSC, using the current revised diagnostic criteria from 2012 Tuberous Sclerosis Consensus Conference.

• #63 Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0870-y

  Our findings reveal a substantially lower age at first diagnosis of TSC. With the advent and implementation of prenatal imaging the diagnosis of TSC is often made early. […] The presence of cardiac rhabdomyoma was associated with cardiac arrhythmias in a substantial number of children in our cohort. Early age at diagnosis will open new avenues to new therapeutic interventions; most importantly early and close EEG monitoring and if abnormal, initiation of early anti-epileptic drug treatment.

• #64 Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0870-y

  Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited. […] The aims of this study were 1) to generate up-to-date data on the incidence of definite or possible TSC, 2) to assess age at first diagnosis, and 3) to compare these data with previous epidemiologic data. […] In total, 86 patients met inclusion criteria (definite or possible TSC) with a median age at diagnosis of 6 months (range: 5 months before birth 197 months of age). […] The annual incidence rate of TSC is estimated at a minimum of 1:17.785 live births. However correcting for underreporting, the estimated incidence rate of definite or possible TSC is approximately 1:6.7601:13.520 live births in Germany. […] This is the first study that assessed prospectively the incidence rate of TSC in children and adolescents using the updated diagnostic criteria of 2012.

• #65 Tuberous Sclerosis Complex: Early Diagnosis in Infants | Pediatric Neurology Briefs

  https://pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-32-12

  Investigators from the Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research conducted two concurrent prospective longitudinal studies to analyze the timing and pattern of clinical presenting symptoms of TSC in infants to facilitate earlier diagnosis and treatment in this specific population. […] There were 130 participants that met diagnostic criteria for TSC. Common initial presenting symptoms were cardiac rhabdomyomas (59%) and hypomelanotic macules (39%), and 85% of the children had either or both. TSC symptoms which led to diagnosis were hypomelanotic macules (94%), tubers and other cortical dysplasias (94%), subpendymal nodules (SENs) (90%), and cardiac rhabdomyomas (82%). […] Thirty-five percent presented before birth, 41% presented at birth or within the first month of life, and 74% were diagnosed within 30 days of presentation.

• #66 SciELO Brazil – Tuberous sclerosis complex: review based on new diagnostic criteria Tuberous sclerosis complex: review based on new diagnostic criteria

  https://www.scielo.br/j/abd/a/qvXj7GRvVrCX7FrXZKtSBRz/

  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. […] 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. […] Diagnostic criteria for tuberous sclerosis were firstly established in 1998. […] In 2012, in the second International Tuberous Sclerosis Complex Consensus Conference held in Washington, these criteria were reviewed with the aim of presenting recommendations for the diagnosis, surveillance and management of TSC patients.

• #67 SciELO Brazil – Tuberous sclerosis complex: review based on new diagnostic criteria Tuberous sclerosis complex: review based on new diagnostic criteria

  https://www.scielo.br/j/abd/a/qvXj7GRvVrCX7FrXZKtSBRz/

  According to the new genetic criterion, the identification of the pathogenic mutation in TSC1 or TSC2 DNA is enough to establish the definitive diagnosis of TSC, configuring an independent diagnostic criterion. […] The definitive diagnosis is defined by the presence of two major criteria or one major and two minor criteria. […] Diagnostic suspicion of TSC comes from the antenatal detection of cardiac rhabdomyomas; the post-natal identification of hypopigmented macules on the skin; seizures in childhood, particularly with spasms; and presence or absence of cognitive impairment during autism assessment. […] The International Tuberous Sclerosis Complex Consensus recommends yearly screening for neuropsychiatric disorders and when clinically indicated. […] There are no specific symptoms for the diagnosis of TSC. However, there are clinical presentations that can occur in the context of TSC that require further investigation.

• #68 Tuberous sclerosis complex – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-us/673

  Tuberous sclerosis complex is an autosomal-dominant, neurocutaneous, multi-system disorder characterised by cellular hyperplasia, tissue dysplasia, and multiple organ hamartomas. […] The disease has two genetic loci: TSC1, found on chromosome 9q34; and TSC2, found on chromosome 16p13. The clinical phenotype can result from a mutation in either of these genes. […] Key diagnostic factors include family history, epilepsy, cardiac rhabdomyoma (single or multiple), renal angiomyolipomas, lymphangioleiomyomatosis of the lung, cerebral subependymal calcified nodules, multiple cortical tubers and/or radial migration lines, giant cell astrocytoma, facial angiofibromas, cephalic plaque(s), non-traumatic ungual or periungual fibromas, hypomelanotic macules, shagreen patch(es) (connective tissue nevus), retinal nodular hamartoma(s), and polycystic kidney disease.

• #69 Tuberous sclerosis complex – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-us/673

  Other diagnostic factors include numerous dental enamel pits and intraoral fibromas, autism, cognitive impairment, and behavioural problems. […] Investigations to consider include genetic testing, brain MRI, neurodevelopmental assessment, electroencephalogram (EEG), ECG, echocardiography, abdominal MRI, glomerular filtration rate (GFR), blood pressure, high-resolution chest CT, pulmonary function tests and 6-minute walk test, skeletal x-ray, colonoscopy, and renal biopsy.

• #70 Diagnosing Tuberous Sclerosis | Children’s Hospital Pittsburgh

  https://www.chp.edu/our-services/brain/neurology/tuberous-sclerosis/diagnosis

  Testing and neuroimaging especially for kids. Our neuro-imaging and testing at the Brain Care Institute are designed especially for children and include the latest technologies and clinical advances. Tests specifically for TSC include: […] Brain magnetic resonance imaging (MRI) […] Clinical findings […] Computed tomography (CT) scan […] Echocardiogram […] Electrocardiogram (EKG) […] Evaluation of the skin […] Eye exam […] Genetic testing […] Renal (kidney) ultrasound […] Woods lamp (ultraviolet light)

• #71 Tuberous sclerosis complex – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-us/673

  Other diagnostic factors include numerous dental enamel pits and intraoral fibromas, autism, cognitive impairment, and behavioural problems. […] Investigations to consider include genetic testing, brain MRI, neurodevelopmental assessment, electroencephalogram (EEG), ECG, echocardiography, abdominal MRI, glomerular filtration rate (GFR), blood pressure, high-resolution chest CT, pulmonary function tests and 6-minute walk test, skeletal x-ray, colonoscopy, and renal biopsy.

• #72 Medical Care for Tuberous Sclerosis Complex Symptoms

  https://www.massgeneral.org/neurology/tsc/patient-education/medical-care

  Because tuberous sclerosis complex (TSC) is a lifelong condition, it is important for all individuals with the disorder to be followed medically from infancy through old age. […] What is clear for all cases, however, is that early diagnosis, careful monitoring, and intervention can dramatically improve the long-term prognosis for people with TSC. […] Collaboration among specialists and the primary, or referring, physician is critical to effective diagnosis and treatment of a person with TSC. […] When physicians suspect that an individual has TSC, they typically perform the following examinations: […] If a TSC diagnosis is confirmed the following additional testing is recommended: […] Following diagnosis, a schedule for routine follow-up care should be established with the individual’s physician or team of physicians.

• #73 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Identifying the clinical pattern and, when possible, a pathogenic gene variant can give a clear diagnosis for an often difficult-to-manage set of symptoms, which has been shown in other epilepsy syndromes and neurodegenerative diseases to be helpful to patients, families, and care partners. Importantly, arriving at a clear diagnosis as early as possible can also guide treatments and provide prognostic information. […] Clinical recognition of TSC is strong enough that genetic testing is often confirmatory only. Typically, diagnosis is made with imaging studies of the brain, heart, and eyes and dermatologic evaluation after a child presents with infantile spasms, although as noted, prenatal detection of cardiac rhabdomyomas may also lead to diagnosis. Family history should be taken and skin examination and neuroimaging done for any child with infantile spasms because these may be key in making a diagnosis of TSC and guiding surveillance of other body systems. Early diagnosis has become more paramount as treatments targeting the mTOR pathway have become available. Diagnostic criteria are provided in Table 2. […] Because of the multisystem nature of TSC and the lifelong course with new symptoms appearing over time, surveillance monitoring is essential. Recommendations for monitoring are provided in Table 3.

• #74 SciELO Brazil – Tuberous sclerosis complex: review based on new diagnostic criteria Tuberous sclerosis complex: review based on new diagnostic criteria

  https://www.scielo.br/j/abd/a/qvXj7GRvVrCX7FrXZKtSBRz/

  According to the new genetic criterion, the identification of the pathogenic mutation in TSC1 or TSC2 DNA is enough to establish the definitive diagnosis of TSC, configuring an independent diagnostic criterion. […] The definitive diagnosis is defined by the presence of two major criteria or one major and two minor criteria. […] Diagnostic suspicion of TSC comes from the antenatal detection of cardiac rhabdomyomas; the post-natal identification of hypopigmented macules on the skin; seizures in childhood, particularly with spasms; and presence or absence of cognitive impairment during autism assessment. […] The International Tuberous Sclerosis Complex Consensus recommends yearly screening for neuropsychiatric disorders and when clinically indicated. […] There are no specific symptoms for the diagnosis of TSC. However, there are clinical presentations that can occur in the context of TSC that require further investigation.

• #75 Diagnostic criteria – TSC Alliance

  https://www.tscalliance.org/understanding-tsc/diagnosis-criteria/

  In 2021, the International Tuberous Sclerosis Complex Consensus Group reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria published in 2013. Clinical features of TSC and genetic testing provide two ways of obtaining a diagnosis of TSC. […] The clinical and genetic diagnostic criteria of 2021 are summarized below: […] 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.

• #76 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  Tuberous sclerosis complex is highly variable in clinical presentation and findings. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. […] Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). […] The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals. […] The recommendation of the Genetics Panel was to make identification of a pathogenic mutation in TSC1 or TSC2 an independent diagnostic criterion, sufficient for the diagnosis or prediction of TSC regardless of the clinical findings.

• #77 Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0764-z

  Tuberous sclerosis complex (TSC) is a genetic disorder with an incidence of 1:6000 live births and associated with the development of benign tumors in several organs. […] The aim of this study was to define the most useful approach to make the diagnosis of TSC before seizure onset (before age 4th months), in order to start early EEG monitoring with possible preventative treatment intervention. […] Early diagnosis of TSC, before seizure onset, is feasible and it is becoming pivotal for epilepsy management and improvement of cognitive outcome. Early TSC diagnosis is mostly based on clinical signs. Brain MRI, echocardiography, skin examination and genetic testing should be performed early in every patient suspected of having TSC. […] In the light of the recent studies and recommendations, it is therefore essential to make a diagnosis of TSC as soon as possible, in order to allow epileptogenic treatment before seizure onset, with a view to improvement of clinical outcome.

• #78 Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0764-z

  The diagnosis of TSC was confirmed in children with at least two major criteria or one major and two minor, or when a pathogenic mutation in either TSC1 or TSC2 was identified. […] Our study shows that early diagnosis of TSC, before clinical seizure onset, is feasible. In the vast majority of our patients (82/100, 82.0%) the diagnosis was established before the end of the 4th month of life (16 weeks), which is regarded as the usual time of clinical seizure onset. […] Therefore, as children diagnosed with TSC before seizure onset have better prognosis it needs to be emphasized that early TSC diagnosis is becoming pivotal and should be established as soon as possible.

• #79 Tuberous Sclerosis Complex – Child Neurology Foundation

  https://www.childneurologyfoundation.org/disorder/tuberous-sclerosis-complex/

  The team involved in treating patients with TSC is usually very large. It can include: Neurologists, Neuropsychologists, Psychologists, Neurosurgeons, Nephrologists, Cardiologists, Pulmonologists, Primary care pediatricians. […] 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. […] 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.

• #80 Tuberous Sclerosis Complex Workup: Diagnostic Criteria, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/1177711-workup

  Under optimal circumstances, molecular genetic testing identifies mutations in up to 75-80% of individuals with tuberous sclerosis complex (TSC). Therefore, a negative genetic diagnostic test result does not exclude a diagnosis of TSC. […] EEG should be performed in patients with tuberous sclerosis complex (TSC) in whom seizures are suspected. […] Baseline ECG is recommended for all patients newly diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their presenting symptom.

• #81 Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4080684/

  A significant fraction (10-25%) of TSC patients have no mutation identified by conventional genetic testing. Therefore, a normal result does not exclude TSC. […] The new, updated diagnostic clinical criteria now include 11 major features and six minor features. […] The presence of a shagreen patch was retained as a major feature, but the criterion was updated by deletion of connective tissue nevus because this term encompasses a variety of skin lesions with excessive dermal connective tissue that are not necessarily associated with TSC. […] The finding of more than one retinal hamartoma was determined to be significant and specific enough to retain as a major feature. […] Subependymal nodules and subependymal giant cell astrocytomas will continue to represent two separate major features.

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