Central nervous system manifestations of tuberous sclerosis complex

Lu, Derek S.; Karas, Patrick J.; Krueger, Darcy A.; Weiner, Howard L.

doi:10.1002/ajmg.c.31647

Cited by 37 publications

(29 citation statements)

References 52 publications

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“…In a UK study [42], CKD (stages 3-5) was found more frequently in individuals with TSC of all ages than in the general population at with SEGA in TOSCA) or shunt placement 4.1%) [21]. For a review on neurological manifestations of TSC, please see Lu et al [70].…”

Section: Renal Manifestationsmentioning

confidence: 99%

A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)

Zöllner

Franz

Hertzberg

et al. 2020

Orphanet J Rare Dis

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Objective: This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly the kidneys, brain, skin, eyes, heart, and lungs. Methods: We performed a systematic analysis of the available literature on BOI in TSC according to the PRISMA guidelines. All studies irrespective of participant age that reported on individual and societal measures of disease burden (e.g. health care resource use, costs, quality of life) were included. Results: We identified 33 studies reporting BOI in TSC patients. Most studies (21) reported health care resource use, while 14 studies reported quality of life and 10 studies mentioned costs associated with TSC. Only eight research papers reported caregiver BOI. Substantial BOI occurs from most manifestations of the disorder, particularly from pharmacoresistant epilepsy, neuropsychiatric, renal and skin manifestations. While less frequent, pulmonary complications also lead to a high individual BOI. The range for the mean annual direct costs varied widely between 424 and 98,008 International Dollar purchasing power parities (PPP-$). Brain surgery, end-stage renal disease with dialysis, and pulmonary complications all incur particularly high costs. There is a dearth of information regarding indirect costs in TSC. Mortality overall is increased compared to general population; and most TSC related deaths occur as a result of complications from seizures as well as renal complications. Long term studies report mortality between 4.8 and 8.3% for a follow-up of 8 to 17.4 years. Conclusions: TSC patients and their caregivers have a high burden of illness, and TSC patients incur high costs in health care systems. At the same time, the provision of inadequate treatment that does not adhere to published guidelines is common and centralized TSC care is received by no more than half of individuals who need it, especially adults. Further studies focusing on the cost effectiveness and BOI outcomes of coordinated TSC care as well as of new treatment options such as mTOR inhibitors are necessary.

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Section: Renal Manifestationsmentioning

confidence: 99%

A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)

Zöllner

Franz

Hertzberg

et al. 2020

Orphanet J Rare Dis

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“…They are thought to be caused by a failure of cellular differentiation and neuronal migration during neurodevelopment [59]. Radial migration lines occur due to a similar process and can be observed with the tubers [45]. The cortical tubers contain giant dysplastic neurons and astrocytes, and they tend to stay stable in size [60].…”

Section: Neurologic Manifestationsmentioning

confidence: 92%

“…Despite the potential of TSC to involve any organ system in the body, some organs are more affected than others. Neurologic manifestations, including seizures and cognitive impairment, are the primary source of patient and caretaker burden, followed by renal abnormalities [45,46].…”

Section: Clinical Presentationmentioning

confidence: 99%

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Tuberous sclerosis: a review of the past, present, and future

Uysal¹,

Şahin²

2020

Turk J Med Sci

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Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in several organs. With the advent of genetic and molecular techniques, mutations in the TSC1 or TSC2 genes were discovered to be responsible for mTOR overactivation, which is the underlying mechanism of pathogenesis. TSC is a highly heterogenous clinical entity with variable presentations and severity of disease. The brain, heart, skin, eyes, kidneys, and lungs are commonly involved in this syndrome, with neurologic symptoms comprising a significant source of morbidity and mortality. In 2012, the diagnostic criteria for TSC were revised by the International Tuberous Sclerosis Complex Consensus panel, and genetic testing was incorporated into the guidelines. Early detection of cardiac rhabdomyomas or TSC-associated skin lesions can suggest the diagnosis and underlie the importance of clinical vigilance. Animal studies have demonstrated the benefit of using mTOR inhibitors for various symptoms of TSC, and they have been successfully translated into clinical trials with significant improvement in symptom burden. Subependymal giant cell astrocytomas, renal angiomyolipomas, and epilepsy are the three FDA-approved indications in relation to TSC for the use of everolimus, which is a first generation mTOR inhibitor. Rapamycin has been FDA approved for lymphangioleiomyomatosis. Other TSC symptoms that could potentially benefit from this class of medication are currently under investigation. TSC constitutes a unique combination of protean physical symptoms and neurobehavioral abnormalities. TSC associated neuropsychiatric disorders (TAND), including intellectual disability, mood disorders, and autism spectrum disorder, represent significant challenges but remain underdiagnosed and undertreated. The TAND checklist is a useful tool for routine use in the clinical evaluation of TSC patients. A multidisciplinary treatment plan, based on the specific problems and needs of individuals, is the key to management of this genetic condition. Ongoing research studies have been providing promising leads for developing novel mechanistic strategies to address the pathophysiology of TSC.

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“…Tuberous sclerosis complex (TSC), an autosomal dominant inherited disease caused by TSC1 or TSC2 mutation, affects approximately 2,000,000 individuals worldwide and has the typical clinical manifestations of hamartomas in multiple organs throughout the body, including the brain, skin, kidney, lung, eye, and heart [ 1 ]. Especially, the disorders of epilepsy, intellectual disability, autism, and other structural lesions occurred in the brain are the leading cause of morbidity and mortality for TSC patients [ 2 ]. Of which, epilepsy is most common, accounting for 70-90% [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

Shao

Chang

2020

BioMed Research International

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Epilepsy is most common in patients with tuberous sclerosis complex (TSC). However, in addition to the challenging treatment, the pathogenesis of epilepsy is still controversial. To determine the transcriptome characteristics of perituberal tissue (PT) and clarify its role in the pathogenesis of epilepsy, GSE16969 was downloaded from the GEO database for further study by comprehensive bioinformatics analysis. Identification of differentially expressed genes (DEGs), functional enrichment analysis, construction of protein-protein interaction (PPI) network, and selection of Hub genes were performed using R language, Metascape, STRING, and Cytoscape, respectively. Comparing with cortical tuber (CT), 220 DEGs, including 95 upregulated and 125 downregulated genes, were identified in PT and mainly enriched in collagen-containing extracellular matrix and positive regulation of receptor-mediated endocytosis, as well as the pathways of ECM-receptor interaction and neuroactive ligand-receptor interaction. As for normal cortex (NC), 1549 DEGs, including 30 upregulated and 1519 downregulated genes, were identified and mainly enriched in presynapse, dendrite and axon, and also the pathways of dopaminergic synapse and oxytocin signaling pathway. In the PPI network, 4 hub modules were found between PT and CT, and top 5 hub modules were selected between PT and NC. C3, APLNR, ANXA2, CD44, CLU, CP, MCHR2, HTR1E, CTSG, APP, and GNG2 were identified as Hub genes, of which, C3, CD44, ANXA2, HTR1E, and APP were identified as Hub-BottleNeck genes. In conclusion, PT has the unique characteristics different from CT and NC in transcriptome and makes us further understand its importance in the TSC-associated epilepsy.

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Central nervous system manifestations of tuberous sclerosis complex

Cited by 37 publications

References 52 publications

A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)

A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)

Tuberous sclerosis: a review of the past, present, and future

The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

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