HY lecture notes:
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 does that mean.”
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 15 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 Hippel–Lindau (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) / arteriovenous malformation (AVM)
- Glaucoma
Arteriovenous malformation (AVM) can also cause SIADH.
In addition, pulmonary AVMs are seen in hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).
- Autosomal dominant
- Cutaneous telangiectasias.
- Epistaxis (nosebleeding) is super common from an early age.
- Can also cause GI bleeding leading to iron deficiency anemia.
- USMLE will always show you a picture of a tongue or fingernail with a red dot, which is the telangiectasia.
- Pulmonary AVMs can be seen. USMLE will show you the tongue and then say 44M has dysnpea and high-output cardiac failure; why? Answer is pulmonary AVM.
AVMs can cause bounding pulses (wide pulse pressure; big difference between systolic and diastolic pressure, e.g., 160/60, or 120/40) similar to aortic regurgitation (and sometimes patent ductus arteriosus) because blood quickly leaves the arterial circulation for the venous circulation.
