Phakomatoses

Phakomatoses is that obscure term that pretty much causes every convo with a student to go like this:

“Wait, what… what did you just say.”

“Phakomatoses.”

“Phakomatoses?? What the fuck is that.”

Phakomatoses are neurocutaneous disorders and refer to:

  • NF1, NF2, TSC, VHL, and Sturge-Weber.

Neurofibromatosis type I (NF1)

  • Chromosome 17
  • Autosomal dominant
  • Neurofibromas (benign cutaneous nerve tumors presenting as small, soft bumps on the skin)
  • Axillary and groin freckling
  • Lisch nodules (iris hamartomas)
  • Cafe au lait spots (hyperpigmented macules)
  • Pheochromocytoma
  • Optic nerve glioma
  • Glioblastoma multiforme
  • Demonstrates variable expressivity

Neurofibromatotis type II (NF2)

  • Chromosome 22
  • Autosomal dominant
  • Bilateral acoustic schwannomas
  • Congenital cataracts
  • Meningioma, ependymoma, oligodendroglioma, medulloblastoma

Tuberous sclerosis (TSC)

  • TSC1 gene on chromosome 9 coding for hamartin protein, and chromosome 16 coding for tuberin protein.
  • Autosomal dominant
  • Periventricular nodules seen on CT or MRI (tubers)
  • Presents as seizure in young child (Qs like writhing movements in a kid’s sleep)
  • Adenoma sebaceum (angiofibromas; skin-colored papules in a butterfly distribution on the face and in the nasolabial folds)
  • Subungual fibromas (nailbed tumors)
  • Cardiac rhabdomyoma
  • Renal angiomyolipoma
  • Pulmonary lymphangioleiomyomatosis (abnormal smooth muscle proliferation of airways; can also affect pregnant women who do not have TSC)

von HippelLindau (VHL)

  • Chromosome 3
  • Autosomal dominant
  • Cerebellar and retinal hemangioblastomas
  • Bilateral renal cell carcinoma
  • Constitutive activation of hypoxia-inducible factor (HIF), leading to vascular proliferation

Sturge-Weber syndrome

  • Not hereditary; caused by mosaic, somatic mutation in GNAQ gene
  • Unilateral facial Port-wine stain birthmark (but may also present as cutaneous violaceous papules in an ophthalmic-trigeminal nerve distribution)
  • Seizure
  • Ipsilateral leptomeningeal angioma (arachnoid or pia mater vascular tumor)
  • Glaucoma

1. What’s the inheritance pattern of the phakomatoses?

2. Which condition is associated with optic nerve glioma?

 
 
 
 
 

3. Which condition is associated with cardiac rhabdomyoma?

 
 
 
 
 

4. Which condition is associated with renal angiomyolipoma?

 
 
 
 
 

5. Which condition is associated with bilateral renal cell carcinoma?

 
 
 
 
 

6. What are Lisch nodules? Which condition are they seen in?

7. Which condition is associated with meningioma?

 
 
 
 
 

8. What are the chromosome numbers for NF1, NF2, TSC, and VHL?