Tuberous sclerosis is an autosomal-dominant, neurocutaneous syndrome characterised by cellular hyperplasia, tissue dysplasia, and hamartomas involving multiple organs.

Aetiology

• The disease has 2 genetic loci:
  • TSC1, found on chromosome 9q34 - hamartin;
  • TSC2, found on chromosome 16p13 - tuberin;
• The clinical phenotype can result from a mutation in either of these genes.
• These genes are tumour suppressor genes, the hamartin-tuberin protein complex normally inactivates a protein called mechanistic target of rapomycin (mTOR) - which normally speeds up the cell cycle by its effect on protein synthesis
• Therefore, as mTOR is not switched off = increased tissue growth and hamartoma formation

Clinical features

Cutaneous features

• depigmented 'ash-leaf' spots which fluoresce under UV light
• roughened patches of skin over lumbar spine (Shagreen patches)
• adenoma sebaceum (angiofibromas): butterfly distribution over nose
• fibromata beneath nails (subungual fibromata)
• Facial angiofibromas
• café-au-lait spots* may be seen

Neurological features

• developmental delay
• epilepsy (infantile spasms or partial)
• intellectual impairment