Book chapter
Tuberous sclerosis complex
Handbook of Clinical Neurology, pp 813-822
2018
PMID: 29478616
Abstract
Tuberous sclerosis complex (TSC) is an autosomal-dominant or sporadic multisystem disorder that results from mutations in either TSC1 or TSC2. The primary organs affected include the brain, skin, lung, kidney, and heart, all with variable frequency, penetrance, and severity. There are over 2000 known allelic variants for TSC, including nonsense and misssense mutation, and all pathogenic mutations are inactivating, leading to loss-of-function effects on the encoded proteins, TSC1 and TSC2. These proteins form a complex to constitutively inhibit the mammalian target of rapamycin (mTOR) signaling cascade, and as a consequence, mTOR signaling is constitutively active within all TSC-associated lesions. The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce renal and brain lesion size, and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. The clinical application of mTOR inhibitors in TSC has provided one of the first examples of precision medicine in a neurodevelopmental disorder.
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44 citations in Scopus
Details
- Title
- Tuberous sclerosis complex
- Creators
- Daphne M. Hasbani - St. Christopher's Hospital for ChildrenPeter B. Crino - University of Maryland, Baltimore
- Publication Details
- Handbook of Clinical Neurology, pp 813-822
- Publisher
- Elsevier Health Sciences
- Resource Type
- Book chapter
- Language
- English
- Academic Unit
- Pediatrics
- Scopus ID
- 2-s2.0-85045874177
- Other Identifier
- 991019174902604721