Neurocutaneous Syndomes

Von Hippel Lindau Syndrome:

• Autosomal dominant
• Gene defect: VHL gene, tumor suppressor gene on chromosome 3
  
• Conditions associated with it include:
  • Renal cell carcinoma
  • Hemangioblastomas
  • Pheochromocytomas
  • Angiomatosis
  • Cysts in the pancreas, liver, and kidneys

Neurofibromatosis type 1:

• Also known as Von Recklinghausen Disease
• Autosomal dominant
• Gene defect: NF1 gene on chromosome 17, codes for the Neurofibromin protein
• Features of NF 1: “CAFE SPOTS”
  • Café-au-lait spots (multiple, >6, >5 mm in children or >15 mm in adults)
  • Axillary or inguinal freckling
  • Family history (autosomal dominant inheritance)
  • Eye findings (Lisch nodules on the iris)
  • Skin neurofibromas (benign tumors)
  • Plexiform neurofibromas (larger, deeper tumors)
  • Optic pathway gliomas (tumors of the optic nerve)
  • Tibial dysplasia (bone abnormalities, e.g., bowing of the tibia)
  • Skeletal abnormalities (e.g., scoliosis)

Neurofibromatosis type 2:

• Autosomal dominant
• Gene defect: NF2 gene on chromosome 22 that codes for the Merlin protein
• Features: "MISME"
  • Multiple schwannomas (bilateral vestibular schwannomas are hallmark)
  • Intracranial meningiomas
  • Spinal tumors (ependymomas, schwannomas)
  • Meningiomas (intracranial or spinal)
  • Ependymomas (spinal cord tumors)

Tuberous sclerosis:

• Autosomal dominant
• Mutation in the TSC 1 gene on chromosome 9 and TSC 2 on chromosome 16
• Features: “HAMARTOMAS”
  • Hamartomas in skin and CNS
  • Ash-leaf spots (Hypopigmented macules)
  • Mitral regurgitation
  • Angiofibromas (adenoma sebaceum)
  • Rhabdomyomas of the heart
  • Tuberous sclerosis
  • Autosomal dOMinant
  • Angiomyolipomas
  • Seizures and shagreen patches
  • Also associated with intellectual disability

Sturge Weber Syndrome

• Also known as encephalotrigeminal angiomatosis
• Somatic mosaicism due to mutation in GNAQ gene
• Features: “STURGE - I”
  • Portwine Stain (Nevus flammeus)
  • Tram track calcifications (leptomeningeal angioma)
  • Unilateral weakness
  • Retinal detachment and atrophy
  • Glaucoma
  • Epilepsy
  • Intellectual disability