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Recent advances: Advances in the understanding of tuberous sclerosis
- Source :
- Archives of Disease in Childhood. 83:140-142
- Publication Year :
- 2000
- Publisher :
- BMJ, 2000.
-
Abstract
- Medical textbooks still define tuberous sclerosis (TSC) as a triad of clinical features, mental retardation, epilepsy and “adenoma sebaceum”, first described by Vogt in 1908.1 2 Not surprisingly therefore many clinicians still do not realise that half of TSC sufferers will have normal intellect, a quarter will not have epilepsy, and almost any organ in the body can be affected. Recent advances in molecular genetics and imaging have begun to unravel the complexity of the disease, explaining the mechanisms behind the clinical features and providing insights into how these patients should be managed. Gunther and Penrose described the autosomal dominant pattern of inheritance of TSC in 1935.3 We now know that there are two genes (and probably only two) causing the TSC clinical phenotype. TSC1 is found on the long arm of chromosome 9, and its protein product is called hamartin.4 The TSC2 gene's protein product is named tuberin and it is situated on the short arm of chromosome 16, only 48 base pairs of DNA from the gene for adult onset polycystic kidney disease (PKD1).5 This genetic heterogeneity in TSC raises the question of whether the clinical syndrome produced by the two different genes is the same. In some conditions, neurofibromatosis for example, genetic heterogeneity helps explain clinically distinct forms of the disease. However, all the complications of TSC have been seen in both TSC1 and TSC2 except for the contiguous gene deletion syndrome (see below). There may, however, be subtle differences in the phenotype produced by the two genes or by specific mutations. There is already some evidence from case series that mutations in TSC2 tend to produce more severe disease than TSC, but this needs to be confirmed in larger less biased studies.6 We may then see no significant differences in the …
- Subjects :
- Genetics
congenital, hereditary, and neonatal diseases and abnormalities
Pathology
medicine.medical_specialty
PKD1
business.industry
Genetic heterogeneity
medicine.disease
Tuberous sclerosis
Chromosome 16
medicine.anatomical_structure
Pediatrics, Perinatology and Child Health
medicine
Polycystic kidney disease
TSC1
medicine.symptom
TSC2
business
Adenoma sebaceum
Subjects
Details
- ISSN :
- 00039888
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Archives of Disease in Childhood
- Accession number :
- edsair.doi...........bd1a2d765bf20b3f4be9dc735e699a65