Neuro - Pathology (Neurocutaneous disorders)

Question 1

What are 4 examples of Neurocutaneous disorders?

Answer 1

(1) Strurge-Weber syndrome (2) Tuberous sclerosis (3) Neurofibromatosis type I (von Recklinghausen disease) (4) von Hippel-Lindau disease

Question 2

What kind of anomaly is Sturge-Weber syndrome? What is its associated defect?

Answer 2

Congenital, non-inherited (somatic), developmental anomaly of neural crest derivatives (mesoderm/ectoderm) due to activating mutation of GNAQ gene.

Question 3

What are 4 key signs/symptoms associated with Sturge-Weber syndrome?

Answer 3

(1) Affects small (capillary-sized) blood vessels –> port-wine staining of the face (non-neoplastic “birthmark in CN V1/V2 distribution) (2) Ipsilateral leptomeningeal angioma –> seizures/epilepsy (3) Intellectual disability (4) Episcleral hemangioma –> high IOP –> early-onset glaucoma

Question 4

What is a mnemonic to remember key associations to make with Sturge-Weber syndrome?

Answer 4

STURGE-Weber: Sporadic, port-wine Stain; Tram track Ca2+ (opposite gyri); Unilateral; Retardation; Glaucoma, GNAQ gene; Epilepsy

Question 5

What are 9 key associations to make with Tuberous sclerosis?

Answer 5

HAMARTOMAS: (1) Hamartomas in CNS and skin (2) Angiofibromas (3) Mitral regurgitation (4) Ash-leaf spots (5) cardiac Rhabdomyoma… [Tuberous sclerosis]… (6) autosomal dOminant (7) Mental retardation (8) renal Angiomyolipoma (9) Seizures, Shagreen patches

Question 6

What are 2 types of masses that have higher incidence in Tuberous sclerosis patients?

Answer 6

Increased incidence of subependymal astrocytomas and ungual fibromas

Question 7

What is another name for Neurofibromatosis type I?

Answer 7

Neurofibromatosis type I (von Recklinghausen disease)

Question 8

What are 3 signs/symptoms associated with Neurofibromatosis type I (von Recklinghausen disease)? What are 2 types of masses also associated with this disorder?

Answer 8

Cafe-au-lait spots, Lisch nodules (pigmented iris hamartomas), neurofibromas in skin… Optic gliomas, pheochromocytomas

Question 9

What is the genetic defect of Neurofibromatosis type I (von Recklinghausen disease)?

Answer 9

Mutated NF1 tumor suppressor gene (neurofibromin, a negative regulator of Ras) on chromosome 17

Question 10

From where are the skin tumors of NF-1 derived?

Answer 10

Skin tumors of NF-1 are derived from neural crest cells.

Question 11

What are the 4 types of masses associated with von Hippel-Lindau disease?

Answer 11

(1) Cavernous hemangiomas in skin, mucosa, organs; (2) Bilateral renal cell carcinomas; (3) Hemangioblastoma (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerebellum; (4) Pheochromocytomas

Question 12

What is the mode of inheritance for von Hippel-Lindau disease?

Answer 12

Autosomal dominant

Question 13

What is the pathogenesis of von Hippel-Lindau disease?

Answer 13

Autosomal dominant; mutated VHL tumor suppressor gene on chromosome 3, which results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors