Familial tumour syndromes: tuberous sclerosis complex

2017 ◽  
Author(s):  
Howard Weiner ◽  
Peter B. Crino
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Attention Deficit Disorder ◽  
Genetic Disorder ◽  
Mammalian Target Of Rapamycin ◽  
Treatment Modalities ◽  
Cognitive Disability ◽  
Developmental Abnormalities ◽  
Cortical Dysplasias ◽  
Cellular Pathogenesis

Tuberous sclerosis complex (TSC) is a multisystem, genetic disorder that results from mutations in TSC1 or TSC2 genes. Neurological and neuropsychiatric disabilities include epilepsy, intellectual disability, autism, attention deficit disorder, and generalized anxiety. Cortical dysplasias (also known as tubers) are developmental abnormalities of the cerebral cortex that are believed to be responsible for seizures, cognitive disability, and autism. Subependymal giant cell astrocytomas (SEGAs) are intraventricular tumours that can cause hydrocephalus, increased intracranial pressure, and death. TSC results from hyperactivation of the mammalian target of rapamycin (mTOR) pathway in neurons in the brain. This chapter reviews the clinical presentations of TSC as well as diagnostic approaches for epilepsy and SEGAs. It discusses the genetics and cellular pathogenesis of TSC as well as reviewing the link to mTOR signalling. This chapter also presents evidence for different treatment modalities for seizures and SEGAs. It is written for qualified specialist physicians and caregivers.

Tuberous sclerosis complex renal disease

2015 ◽  
Author(s):  
Bradley P. Dixon ◽  
J. Christopher Kingswood ◽  
John J. Bissler
Keyword(s):  
Renal Failure ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Mammalian Target Of Rapamycin ◽  
Cystic Disease ◽  
Pulmonary Lymphangioleiomyomatosis ◽  
Brain Involvement ◽  
Almost All

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting almost all organs. It has wider phenotypic variation than often appreciated, with less than half showing the combination of characteristic facial angiofibromas, epilepsy, and mental retardation. Renal angiomyolipomata or cysts are found in 90% and renal failure was historically a common mode of adult death from the disease. Pulmonary lymphangioleiomyomatosis is restricted to females. Angiomyolipomata or cystic disease, or both, may cause renal failure. Angiomyolipomata may also haemorrhage, especially from larger lesions. Manifestations of brain involvement substantially complicate management of many patients with TSC. The causative genes TSC1 and TSC2 encode tuberin and hamartin which are involved in control of the mammalian target of rapamycin pathway. Inhibitors of that pathway, such as sirolimus and everolimus, are therefore logical approaches to therapy and have been shown to be effective in reducing angiomyolipomata volume. It remains to be seen whether they can protect renal function.

scholarly journals RARE-25. RETINAL ASTROCYTOMA mTOR INHIBITOR THERAPY IN TUBEROUS SCLEROSIS MOSAICISM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii447-iii447
Author(s):  
Naomi Evans ◽  
Katherine Paton ◽  
Harinder Kaur Gill ◽  
Juliette Hukin
Keyword(s):  
Optic Nerve ◽  
Retinal Detachment ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Neovascular Glaucoma ◽  
Renal Angiomyolipoma ◽  
Gradual Reduction ◽  
Health Canada

Abstract INTRODUCTION Everolimus is an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), it is Health Canada and FDA approved for SEGA and renal angiomyolipoma in the setting of tuberous sclerosis complex (TSC). There is little data available in regards to this treatment of TSC associated retinal astrocytoma (RA). Although the behaviour of RA is often indolent or slowly progressive, aggressive behaviour with retinal detachment and neovascular glaucoma requiring enucleation has been reported in several patients. Definite TSC diagnosis is established when either two major features or one major and two minor features are present. Probable TSC diagnosis is established when one major plus one minor feature is present. METHODS We report a child with probable TSC mosaicism, with negative serum NGS for TSC but RA and retinal achromic patch on the left. A left retinal peripapillary astrocytoma around optic nerve and very close to fovea was noted. There was concern that if it grew or there were to be any leakage it would cause visual impairment. This lead to therapy with everolimus 4.5 mg/m2/d aiming for level between 5 and 10 mcg/L. RESULTS This boy has had a gradual reduction of the RA over the last 29 months, with healthy retina in the region no longer occupied by the lesion and preserved vision. He has tolerated therapy well with occasional mouth ulcers. CONCLUSION mTORC1 inhibition is effective therapy to preserve vision in the setting of retinal astrocytoma and tuberous sclerosis mosaicism.

TUBEROUS SCLEROSIS: PRESENTATION OF A CASE AND REVIEW OF THE LITERATURE

2021 ◽  
pp. 95-96
Author(s):  
Fabricio Andrés Lasso Andrade ◽  
Jorge Alejandro Cadena Arteaga ◽  
Ángela Maria Fajardo Arteaga ◽  
Viviana Lizeth Echeverry Morillo ◽  
David Alfredo Acevedo Vargas ◽  
...  
Keyword(s):  
Nervous System ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Causal Link ◽  
Benign Tumors ◽  
Review Of The Literature ◽  
Dominant Inheritance ◽  
Variable Expression

Tuberous Sclerosis Complex (TSC) also known as Bournneville disease. TSC is a multisystemic genetic disorder with autosomal dominant inheritance, of variable expression, which is mainly characterized by the presence of benign tumors or hamartomas in the nervous system and skin, but which may also be present in the heart, kidney, lung and other organs. The most frequent symptom is epilepsy, affecting 80-90% of patients with TSC which manifests itself in childhood between 1 to 3 years of age. We present a case of sporadic onset tuberous sclerosis with epilepsy that had a causal link with TSC after admission to the emergency room in a convulsive status.

scholarly journals The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex

2019 ◽  
Vol 30 (4) ◽  
pp. 2199-2214
Author(s):  
Benoit Scherrer ◽  
Anna K Prohl ◽  
Maxime Taquet ◽  
Kush Kapur ◽  
Jurriaan M Peters ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Face Processing ◽  
Genetic Disorder ◽  
Neuropsychiatric Symptoms ◽  
Autism Spectrum ◽  
The Body ◽  
Fusiform Gyrus ◽  
Benign Tumors ◽  
Anatomical Connectivity

Abstract Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors throughout the body; it is generally diagnosed early in life and has a high prevalence of autism spectrum disorder (ASD), making it uniquely valuable in studying the early development of autism, before neuropsychiatric symptoms become apparent. One well-documented deficit in ASD is an impairment in face processing. In this work, we assessed whether anatomical connectivity patterns of the fusiform gyrus, a central structure in face processing, capture the risk of developing autism early in life. We longitudinally imaged TSC patients at 1, 2, and 3 years of age with diffusion compartment imaging. We evaluated whether the anatomical connectivity fingerprint of the fusiform gyrus was associated with the risk of developing autism measured by the Autism Observation Scale for Infants (AOSI). Our findings suggest that the fusiform gyrus connectivity captures the risk of developing autism as early as 1 year of age and provides evidence that abnormal fusiform gyrus connectivity increases with age. Moreover, the identified connections that best capture the risk of developing autism involved the fusiform gyrus and limbic and paralimbic regions that were consistent with the ASD phenotype, involving an increased number of left-lateralized structures with increasing age.

scholarly journals Loss of Tuberous Sclerosis Complex-2 Function and Activation of Mammalian Target of Rapamycin Signaling in Endometrial Carcinoma

2008 ◽  
Vol 14 (9) ◽  
pp. 2543-2550 ◽  
Author(s):  
Karen H. Lu ◽  
Weiguo Wu ◽  
Bhuvanesh Dave ◽  
Brian M. Slomovitz ◽  
Thomas W. Burke ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin

Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex

2020 ◽  
Vol 58 (1) ◽  
pp. 25-31
Author(s):  
Pierre Pfirmann ◽  
Jerome Aupy ◽  
Eva Jambon ◽  
Laetitia Idier ◽  
Mathilde Prezelin-Reydit ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Multidisciplinary Approach ◽  
Genetic Disorder ◽  
Multidisciplinary Care ◽  
Adult Patients ◽  
Bone Lesions ◽  
Interdisciplinary Management ◽  
Cutaneous Lesions ◽  
High Level

BackgroundTuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines.ObjectivesOur study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model.MethodsData on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually.Results90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27–47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC.ConclusionWe obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction.

Fetal Echocardiographic Detection of Cardiac Tumors: A Case Report of Multiple Fetal Cardiac Rhabdomyomas

2019 ◽  
Vol 35 (5) ◽  
pp. 426-430
Author(s):  
Bailey Sarff ◽  
Randall Floyd ◽  
Amy Bildner ◽  
Janell Stormo ◽  
Kelsy Fisher
Keyword(s):  
Case Report ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cardiac Tumor ◽  
Genetic Disorder ◽  
Cardiac Tumors ◽  
Size Number

Cardiac rhabdomyomas are the most common fetal cardiac tumor. They can be detected in the second and third trimesters. Rhabdomyomas are most commonly associated with the genetic disorder tuberous sclerosis complex. When associated with tuberous sclerosis complex, cardiac rhabdomyomas usually regress within the first few years of life, without complications. Symptoms depend on the size, number, and location of the rhabdomyomas. A case report of multiple cardiac rhabdomyomas that was found at 35 weeks’ gestation and is discussed.

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