Tuberous sclerosis complex (TSC), also known as Bourneville disease, is a rare autosomal dominant genetic disorder characterized by the growth of numerous benign tumors throughout the body, including the brain, skin, kidneys, heart, and lungs[@northrup2021]. It affects approximately 1 in 6,000 to 1 in 10,000 live births and has a prevalence of about 1 in 20,000.
TSC results from mutations in the TSC1 or TSC2 genes, leading to dysregulated [mTOR](/mechanisms/mtor-signaling-pathway) (mammalian target of rapamycin) signaling and abnormal cell growth and proliferation[@henske2016].
Mutations in TSC2 account for approximately 70% of cases and typically cause a more severe phenotype. Approximately 15-20% of cases are caused by TSC1 mutations, while 10-15% have no identified mutation.
mTOR Pathway Dysregulation
The TSC1/TSC2 complex normally inhibits mTORC1 (mammalian target of rapamycin complex 1) signaling. Loss-of-function mutations lead to:
Constitutive mTORC1 activation
Uncontrolled cell growth and proliferation
Increased protein synthesis
Enhanced cell survival
Clinical Features
Neurological Manifestations
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Tuberous Sclerosis Complex
Overview
Tuberous sclerosis complex (TSC), also known as Bourneville disease, is a rare autosomal dominant genetic disorder characterized by the growth of numerous benign tumors throughout the body, including the brain, skin, kidneys, heart, and lungs[@northrup2021]. It affects approximately 1 in 6,000 to 1 in 10,000 live births and has a prevalence of about 1 in 20,000.
TSC results from mutations in the TSC1 or TSC2 genes, leading to dysregulated [mTOR](/mechanisms/mtor-signaling-pathway) (mammalian target of rapamycin) signaling and abnormal cell growth and proliferation[@henske2016].
Mutations in TSC2 account for approximately 70% of cases and typically cause a more severe phenotype. Approximately 15-20% of cases are caused by TSC1 mutations, while 10-15% have no identified mutation.
mTOR Pathway Dysregulation
The TSC1/TSC2 complex normally inhibits mTORC1 (mammalian target of rapamycin complex 1) signaling. Loss-of-function mutations lead to:
Constitutive mTORC1 activation
Uncontrolled cell growth and proliferation
Increased protein synthesis
Enhanced cell survival
Clinical Features
Neurological Manifestations
Epilepsy
Occurs in 80-90% of individuals with TSC
Onset typically in first year of life
Infantile spasms are common
Often refractory to antiepileptic drugs
Consider surgical resection for drug-resistant cases
Cortical Dysplasia
Cortical tubers are hallmark brain lesions
Contribute to epilepsy and cognitive impairment
Number and location correlate with neurological outcomes
Intellectual Disability
Present in approximately 50% of cases
Range from normal intelligence to severe impairment
Correlates with epilepsy severity and number of cortical tubers