TSC1 and TSC2: Tuberous Sclerosis Complex and Its Related Epilepsy Phenotype

2021 ◽  
Author(s):  
Claudia Di Napoli ◽  
Alessia Gennaro ◽  
Carmelania Lupica ◽  
Raffaele Falsaperla ◽  
Roberta Leonardi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Mtor Inhibitor ◽  
Autosomal Dominant ◽  
Treatment Strategies ◽  
Neurological Impairment ◽  
Drug Resistant ◽  
Autosomal Dominant Disorder ◽  
Mechanistic Target Of Rapamycin ◽  
Neuropsychiatric Manifestations

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a multisystemic involvement. In TSC, reduced function of TSC1 and TSC2 genes products (hamartin and tuberin, respectively) leads to an hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and to a consequent cell growth dysregulation. In TSC patients, neurological and neuropsychiatric manifestations, especially epilepsy and neuropsychiatric comorbidities such as autism or intellectual disability, represent the most disabling features. In particular, epilepsy occurrs up to 80% of patients, is often drug resistant and is frequently associated with neurological impairment. Due to the burden of this morbidity, different treatment strategies have been proposed with the purpose to make patients epilepsy free, such as the use of different antiepileptic drugs like vigabatrin, carbamazepine, valproic acid, and levetiracetam. More recently, a mTOR inhibitor (i.e. everolimus) has showed promising results in terms of seizures reduction.

Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex

2019 ◽  
Vol 20 (1) ◽  
pp. 217-240 ◽  
Author(s):  
Catherine L. Salussolia ◽  
Katarzyna Klonowska ◽  
David J. Kwiatkowski ◽  
Mustafa Sahin
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Phenotypic Variability ◽  
Mtor Inhibitors ◽  
Multiple Organ ◽  
Great Promise ◽  
Optimal Timing ◽  
Autosomal Dominant Disorder ◽  
Organ Systems ◽  
Neuropsychiatric Manifestations

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects multiple organ systems due to an inactivating variant in either TSC1 or TSC2, resulting in the hyperactivation of the mechanistic target of rapamycin (mTOR) pathway. Dysregulated mTOR signaling results in increased cell growth and proliferation. Clinically, TSC patients exhibit great phenotypic variability, but the neurologic and neuropsychiatric manifestations of the disease have the greatest morbidity and mortality. TSC-associated epilepsy occurs in nearly all patients and is often difficult to treat because it is refractory to multiple antiseizure medications. The advent of mTOR inhibitors offers great promise in the treatment of TSC-associated epilepsy and other neurodevelopmental manifestations of the disease; however, the optimal timing of therapeutic intervention is not yet fully understood.

scholarly journals Tuberous Sclerosis Complex Associated Lymphangioleiomyomatosis Presenting with Spontaneous Pneumothorax and Renal Angiomyolipomas

2019 ◽  
Vol 48 (2) ◽  
pp. 51-54
Author(s):  
Mohammed Mirazur Rahman ◽  
Shish Mohammad Sarkar ◽  
Manzurul Ibrahim Musa ◽  
Farjana Binte Habib ◽  
Md Nazmul Hasan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Spontaneous Pneumothorax ◽  
Autosomal Dominant ◽  
Multisystem Disorder ◽  
Autosomal Dominant Disorder ◽  
Oxygen Inhalation ◽  
Lower Back ◽  
Thin Walled

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder manifested by involvement of multisystem including skin, central nervous system, heart, kidneys and eyes. Lymphangioleiomyomatosis (LAM) is also a multisystem disorder that primarily affects the lungs. We report a case of tuberous sclerosis complex associated lymphangio-leiomyomatosis (TSC-LAM) in a 26-year-old female patient who was presented with spontaneous pneumothorax and renal angiomyolipomas. In clinical examination; We found multiple angiofibromas over her face, shagreen patches over upper and lower back and ungual fibromas in both fingers and toes. HRCT of chest revealed right sided pneumothorax with multiple thin walled cysts in both lungs. Ultrasonogram (USG) and Computer Tomography (CT) scan of abdomen revealed bilateral angiomyolipomas. We managed her pneumothorax with intercostal chest tube drainage and oxygen inhalation. Bangladesh Med J. 2019 May; 48 (2): 51-54

scholarly journals Tuberous sclerosis complex in a child: diagnosis and management

2010 ◽  
Vol 50 (3) ◽  
pp. 181
Author(s):  
Prastiya Indra Gunawan ◽  
Aminuddin Harahap ◽  
Darto Saharso
Keyword(s):  
Mental Retardation ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autosomal Dominant ◽  
Mental Disability ◽  
Autosomal Dominant Disorder ◽  
Diagnosis And Management ◽  
Child Diagnosis ◽  
Body Tissues ◽  
Lung And Kidney

Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder affecting children and adults, resulted from mutations in one of two genes, TSC1 (encoding hamartin) or TSC2 (encoding tuberin) genes located on chromosomes 9 and 16 respectively.1,2 Synonyms of TSC are Bourneville Pringle syndrome, epiloia, or tuberosclerosis. This disorder is characterized by seizures, mental disability, and small noncancerous tumors on the skin and other body tissues, such as brain, eye, lung, and kidney. The classic triad are seizures, mental retardation, and cutaneous angiofibromas.3

scholarly journals A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Saba Ahmad ◽  
Luis Manon ◽  
Gifty Bhat ◽  
Jerry Machado ◽  
Alice Zalan ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cellular Differentiation ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Disease ◽  
Sacrococcygeal Teratoma ◽  
Dominant Disease ◽  
The Brain

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

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.

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