Tuberous sclerosis complex in a child: diagnosis and management

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

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

Bangladesh Medical Journal ◽

10.3329/bmj.v48i2.51295 ◽

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

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

Journal of Pediatric Neurology ◽

10.1055/s-0041-1727142 ◽

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.

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A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

Human Genome Variation ◽

10.1038/s41439-020-00124-8 ◽

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.

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

10.36106/gjra/4910349 ◽

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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Tuberous Sclerosis Complex - Diagnosis and Management

10.3389/978-2-88971-733-0 ◽

2021 ◽

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Diagnosis And Management

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Tuberous sclerosis complex: a clinical case with multiple ophthalmological manifestations

BMJ Case Reports ◽

10.1136/bcr-2018-226662 ◽

2018 ◽

pp. bcr-2018-226662

Author(s):

Tiago Maio ◽

José Lemos ◽

Jorge Moreira ◽

Filipa Sampaio

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Nerve Palsy ◽

Autosomal Dominant ◽

Obstructive Hydrocephalus ◽

Abducens Nerve ◽

Signs And Symptoms ◽

Optic Discs ◽

Expansive Lesion ◽

Binocular Diplopia

The tuberous sclerosis complex is a rare disease, with autosomal dominant transmission, with multisystemic involvement including ophthalmologic. Retinal hamartomas and retinal achromic patch are the most frequent ocular findings. Other ophthalmic signs and symptoms are relatively rare in this disease.We describe the case of a young woman with tuberous sclerosis who presented with horizontal binocular diplopia and decreased visual acuity without complaints of nausea, vomiting or headache. She had right abducens nerve palsy, pale oedema of both optic discs and retinal hamartomas. An obstructive hydrocephalus caused by an intraventricular expansive lesion was identified in brain CT.Observation by the ophthalmologist is indicated in all confirmed or suspected cases of tuberous sclerosis to aid in clinical diagnosis, monitoring of retinal hamartomas or identification of poorly symptomatic papilloedema.

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Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex

Annual Review of Genomics and Human Genetics ◽

10.1146/annurev-genom-083118-015354 ◽

2019 ◽

Vol 20 (1) ◽

pp. 217-240 ◽

Cited By ~ 10

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.

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Tuberous sclerosis complex renal disease

10.1093/med/9780199592548.003.0330 ◽

2015 ◽

Cited By ~ 1

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.

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