Sturge-Weber syndrome

• Somatic mosaic mutation of GNAQ gene → malformation of capillaries

Tuberous sclerosis

• Mutation of tumor suppressor genes (variable expression) → loss of function → unchecked cell growth → tumor development
• Tumor suppressor genes
  • TSC1 gene on chromosome 9 encodes hamartin protein
  • TSC2 gene on chromosome 16 encodes tuberin protein
• Clinical features
  • Intellectual disability (caused by brain lesions)
  • Seizures
  • Skin manifestations
    • Adenoma sebaceum (facial angiofibroma): benign tumor composed of blood vessels and fibrous connective tissue
      • Mostly located around the nose and cheeks
      • Distribution resembles a butterfly shape
    • Ash-leaf spots: hypopigmented (white) macules on the trunk and extremities
    • Shagreen patch: flesh-colored papule in the lumbosacral region with an orange-peel appearance

von Hippel-Lindau syndrome

• See Hereditary cancer syndromes
• VHL gene: tumor suppressor gene on the short arm of chromosome 3
• Deletion of VHL gene → impaired ubiquitination and elimination of hypoxia-inducible factor 1a → loss of function → tumor and cyst development

Neurofibromatosis

• Etiology
  • Neurofibromatosis type 1 and type 2: autosomal dominant inheritance or spontaneous mutation

Neurofibromatosis type I

• Café-au-lait spots

Mnemonic

If you drink too much coffee, you are gonna go number one.

• Cutaneous neurofibromas
• Optic gliomas

Neurofibromatosis type II