Neurocutaneous Syndromes

Question 1

Phakomatoses

Answer 1

neurological disorders, skin manifestations, harmatomas (benign growths)

mostly genetic

Question 2

NF1

Answer 2

Neurofibromatosis Type 1: most common neurocutaneous syndrome (90%)

Autosomal Dominant or Sporadic

• mutation in neurofibrin protein
• affects all neural crest cells: schwann cells, fibroblasts, melanocytes, osteoblasts, chondrocytes

Question 3

NF1 Manifestations

• systemic (2)
• manifestations (3)
• vision(3)

Answer 3

Mental retardation, seizures, Cafe Au Lait Spots (6+ for dx)

Crowe Sign + Plexiform Neurofibromas (any nerve)

S-Shaped lid + Iris Lisch Nodules + Optic Nerve Glioma

Question 4

NF2

Answer 4

Autosomal Dominant: central fibromatosis
- mutation in merlin protein

Focal Neurological Deficits

Bilateral Vestibular Schwannoma (Acoustic) 85%
- noncancerous inner ear tumor

PSC or Cortical Cataracts 81%

more subtle skin findings

Question 5

Tuberous Sclerosis Complex

• mutation?
• affects what pathway?
• systemic effects?
• manifestations?

Answer 5

Bourneville’s Disease - mutation on hamartin protein or tuberin protein
- 2/3 are spontaneous mutations

Affects mTOR signaling pathway leading to abnormal cell differentiation (can involve ANY organ)

Seizures, Autism, Mental Retardation

Angiofibromoma (adenoma sebaceum) on face
Ash Leaf Spot (hypopigmented spot at birth)
Shagreen Patch 50% usually lower back

Retinal Hamartomas: non-progressive, translucent, flat in periphery

Question 6

Sturge-Weber Syndrome

• genetics?
• Triad?
• Symptoms
• manifestations

Answer 6

Mosaic genetics (more W >>) 
- mutation in GNAQ gene that regulates proteins for blood vessel development

Triad of Vascular Malformations: Eye, Brain, Face

Impaired blood flow, seizures***, Hemiplegia(paralysis of one side)

Facial Hemangioma (Port-Wine Stain): along trigeminal dermatome - usually unilateral

Glaucoma: on side of birthmark and usually with upper eyelid is affected

Choroidal Hemangiomas

Question 7

Von Hippel-Lindau

• genetics
• manifestations (4)

Answer 7

Autosomal Dominant
- mutation in VHL gene leading to renal, pancreatic and epididymis cysts

Hemangioblastomas of CNS: cerebellum, medulla, SC

Renal Cell Carcinoma ~ usually by 60

Pheochromocytoma: benign tumor on adrenal gland
- affects BP and HTN

Retinal Hemangioblastomas: tumors in retina
- multiple of these are diagnostic of VHL

Question 8

Wyburn-Mason Syndrome

Answer 8

not inherited

retinal arteriovenous malformations(AVM) that can hemorrhage (decrease VA or lead to strab)
-Cerebral AVM leads to papilledema, HA, seizures

looks like worms