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The Lancet. Neurology Jul 2015Tuberous sclerosis (also known as tuberous sclerosis complex [TSC]) is a multisystem genetic disorder that affects almost every organ in the body. Mutations in the TSC1... (Review)
Review
Tuberous sclerosis (also known as tuberous sclerosis complex [TSC]) is a multisystem genetic disorder that affects almost every organ in the body. Mutations in the TSC1 or TSC2 genes lead to disruption of the TSC1-TSC2 intracellular protein complex, causing overactivation of the mammalian target of rapamycin (mTOR) protein complex. The surveillance and management guidelines and clinical criteria for tuberous sclerosis were revised in 2012, and mTOR inhibitors are now recommended as treatment options for subependymal giant cell astrocytomas and renal angiomyolipomas-two common features of the disease. However, most morbidity and mortality caused by tuberous sclerosis is associated with neurological and neuropsychiatric manifestations. Treatment of epilepsy associated with tuberous sclerosis remains a major challenge, with more than 60% of patients having ongoing seizures. Tuberous-sclerosis-associated neuropsychiatric disorders (TAND) are multilevel and occur in most individuals with the disorder, but are rarely assessed and treated. Clinical trials of mTOR inhibitors to treat seizures and TAND are underway. Management of the neurological and neuropsychiatric manifestations of the disorder should be coordinated with treatment of other organ systems. In view of the age-related expression of manifestations from infancy to adulthood, continuity of clinical care and ongoing monitoring is paramount, and particular attention is needed to plan transition of patient care from childhood to adult services.
Topics: Clinical Trials as Topic; Humans; Mental Disorders; Nervous System Diseases; Tuberous Sclerosis
PubMed: 26067126
DOI: 10.1016/S1474-4422(15)00069-1 -
Multiple Sclerosis and Related Disorders Mar 2023Tuberous sclerosis (TS) is a monogenic disorder which causes disabling neurological symptoms. Similarly, multiple sclerosis (MS) may result in disability, but in...
Tuberous sclerosis (TS) is a monogenic disorder which causes disabling neurological symptoms. Similarly, multiple sclerosis (MS) may result in disability, but in contrast, is diagnosed without genetic testing. Clinicians are advised to exercise caution in diagnosing MS in the presence of a pre-existing genetic disorder, as it may be a potential 'red flag'. A dual diagnosis of MS and TS has not previously been reported in the literature. We provide two cases of known cases of TS who presented with new neurological symptoms and associated physical signs compatible with a dual diagnosis of TS/MS.
Topics: Humans; Tuberous Sclerosis; Multiple Sclerosis; Genetic Testing
PubMed: 36863086
DOI: 10.1016/j.msard.2023.104586 -
American Journal of Medical Genetics.... Sep 2018Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal-dominant genetic syndrome marked by development of hamartomatous lesions arising from dysfunction of the... (Review)
Review
Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal-dominant genetic syndrome marked by development of hamartomatous lesions arising from dysfunction of the mammalian target of rapamycin (mTOR) pathway. Although TSC remains a heterogeneous clinical entity, the recent inclusion of genetic diagnostic criteria reflects advancement in our understanding of its underlying etiopathogenesis. Abnormal cellular growth, differentiation, and migration result in multisystem sequelae, with neurologic manifestations of TSC representing the primary cause of morbidity and mortality for the majority of individuals. Modern imaging techniques aid in the diagnosis of TSC and guide treatment strategies by revealing central nervous system findings. Cortical tubers are the namesake lesion of the disorder and occur in up to 90% of cases, often exerting significant epileptogenic potential. Subependymal nodules are found in 80% of patients as calcified tumors lining the ependyma of the lateral ventricles. In some cases, these nodules are thought to progress to subependymal giant cell astrocytomas and may present with obstructive hydrocephalus. Retinal astrocytic hamartomas are also common, present in 50% of patients. Surgery remains the treatment of choice for large or symptomatic lesions, though clinical trials have highlighted a potential role for mTOR pathway antagonism. A multidisciplinary approach is necessary for achieving optimal patient outcomes.
Topics: Brain; Epilepsy; Hamartoma; Humans; Mutation; Neurodevelopmental Disorders; Retinal Pigment Epithelium; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein
PubMed: 30230171
DOI: 10.1002/ajmg.c.31647 -
American Journal of Medical Genetics.... Sep 2018Healthcare transition from childhood to adulthood is required to ensure continuity of care of an increasing number of individuals with chronic conditions surviving into... (Review)
Review
Healthcare transition from childhood to adulthood is required to ensure continuity of care of an increasing number of individuals with chronic conditions surviving into adulthood. The transition for patients with tuberous sclerosis complex (TSC) is complicated by the multisystemic nature of this condition, age-dependent manifestations, and high clinical variability and by the presence of intellectual disability in at least half of the individuals. In this article, we address the medical needs regarding each TSC-related manifestation in adulthood, and the services and support required. We review existing models of transition in different chronic conditions, discuss our experience in transitioning from the pediatric to the adult TSC Clinic at our Institution, and propose general rules to follow when establishing a transition program for TSC. Although a generalizable transition model for TSC is likely not feasible for all Institutions, a multidisciplinary TSC clinic is probably the best model, developed in accordance with the resources available and country-specific healthcare systems. Coordination of care and education of the adult team should be always sought regardless of the transition model.
Topics: Adolescent; Adult; Epilepsy; Humans; Intellectual Disability; Italy; Kidney Diseases; Lung Diseases; Patient Care; Transition to Adult Care; Tuberous Sclerosis
PubMed: 30253036
DOI: 10.1002/ajmg.c.31653 -
Journal of Neurodevelopmental Disorders Sep 2023Tuberous sclerosis complex (TSC) is associated with a wide range of physical manifestations for which international clinical recommendations for diagnosis and management...
BACKGROUND
Tuberous sclerosis complex (TSC) is associated with a wide range of physical manifestations for which international clinical recommendations for diagnosis and management have been established. TSC is, however, also associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND) that are typically under-identified and under-treated yet associated with a profound burden of disease. The contemporary evidence base for the identification and treatment of TAND is much more limited and, to date, consensus recommendations for the diagnosis and management of TAND have also been limited and non-specific.
METHODS
The TANDem project was launched with an international, interdisciplinary, and participatory consortium of 24 individuals, including TSC family representatives, from all World Health Organization (WHO) regions but one. One of the aims of the TANDem project was to generate consensus recommendations for the identification and treatment of TAND. At the time of this project, no internationally adopted standard methodology and methodological checklists existed for the generation of clinical practice recommendations. We therefore developed our own systematic procedure for evidence review and consensus-building to generate evidence-informed consensus recommendations of relevance to the global TSC community.
RESULTS
At the heart of the consensus recommendations are ten core principles surrounded by cluster-specific recommendations for each of the seven natural TAND clusters identified in the literature (autism-like, dysregulated behavior, eat/sleep, mood/anxiety, neuropsychological, overactive/impulsive, and scholastic) and a set of wraparound psychosocial cluster recommendations. The overarching recommendation is to "screen" for TAND at least annually, to "act" using appropriate next steps for evaluation and treatment, and to "repeat" the process to ensure early identification and early intervention with the most appropriate biological, psychological, and social evidence-informed approaches to support individuals with TSC and their families.
CONCLUSIONS
The consensus recommendations should provide a systematic framework to approach the identification and treatment of TAND for health, educational, social care teams and families who live with TSC. To ensure global dissemination and implementation of these recommendations, partnerships with the international TSC community will be important. One of these steps will include the generation of a "TAND toolkit" of "what to seek" and "what to do" when difficulties are identified in TAND clusters.
Topics: Humans; Affect; Anxiety; Autistic Disorder; Consensus; Tuberous Sclerosis
PubMed: 37710171
DOI: 10.1186/s11689-023-09500-1 -
Tidsskrift For Den Norske Laegeforening... Mar 2007
Topics: Clinical Competence; Humans; Patient Care Team; Tuberous Sclerosis
PubMed: 17435801
DOI: No ID Found -
European Journal of Human Genetics :... Oct 2006Tuberous sclerosis is a serious inherited disease which poses major challenges for affected families and those caring for them. Identification of the genes causing the...
Tuberous sclerosis is a serious inherited disease which poses major challenges for affected families and those caring for them. Identification of the genes causing the condition and study of their protein products has shed light on the pathogenesis of the disease and provided valuable new information about signalling pathways regulating protein synthesis and cell growth. There is now the exciting possibility of drug therapy for some of the manifestations of the disease.
Topics: Adult; Child, Preschool; Humans; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins
PubMed: 16868562
DOI: 10.1038/sj.ejhg.5201625 -
Archives of Disease in Childhood Dec 1988
Review
Topics: Eye Diseases; Heart Diseases; Humans; Nervous System Diseases; Tuberous Sclerosis
PubMed: 3069050
DOI: 10.1136/adc.63.12.1423 -
Journal of the American Academy of... Aug 2007Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem neurocutaneous syndrome characterized by the development of multiple hamartomas distributed... (Review)
Review
UNLABELLED
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem neurocutaneous syndrome characterized by the development of multiple hamartomas distributed throughout the body, skin, brain, heart, kidneys, liver, and lungs. Two-thirds of patients represent sporadic mutations. The classic triad is seizures, mental retardation, and cutaneous angiofibromas. However, the full triad occurs in only 29% of patients; 6% of them lack all three of them. Two tumor suppressor genes responsible for TSC have been identified: TSC1 gene on chromosome 9 and TSC2 on chromosome 16. This article highlights the most recent significant advances in the diagnosis and genetics of TSC, along with a discussion on the limitations and the usefulness of the revised 1998 clinical criteria for the tuberous sclerosis complex. The "ash leaf" macule often comes in other shapes, such as round; most are polygonal, usually 0.5 cm to 2.0 cm in diameter, resembling a thumbprint. Since the death of its describer, Thomas Fitzpatrick, we call each a "Fitzpatrick patch." Special attention is paid in this work to TSC treatment options, including therapeutic trials with rapamycin, also known as sirolimus.
LEARNING OBJECTIVE
After completing this learning activity, participants should familiar with tuberous sclerosis complex, its cutaneous signs and systemic findings stratified by patient age, its genetics, and the potential for meaningful therapeutic intervention.
Topics: Dermatology; Diagnosis, Differential; Humans; Molecular Diagnostic Techniques; Mutation; Protein Kinases; Sirolimus; Skin Diseases; TOR Serine-Threonine Kinases; Tooth Diseases; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins
PubMed: 17637444
DOI: 10.1016/j.jaad.2007.05.004 -
Pediatric and Developmental Pathology :... 1999
Topics: History, 19th Century; History, 20th Century; Humans; Tuberous Sclerosis
PubMed: 9949228
DOI: 10.1007/s100249900110