Syndromes

Question 1

Tuberous Sclerosis

Answer 1

Hamartomas in CNS and skin

Angiofibromas, mitral regurgitation, ash leaf spots, cardiac rhabdomyoma, mental retardation, renal angomyolipoma (bilateral)
Seizures, Shagreen patches

increased incidence of subependymal astrocytomas and ungual fibromas

AD

Question 2

Neurofbromatosis type I

Answer 2

AD

Cafe au lait spots
Lisch nodules (Pigmented iris harmartomas), neurofibromas in skin (buttonhole on pressure), optic gliomas (vision loss), pheochromocytomas, axillary or inguinal freckles, sphenoid dysplasia, pseudoarthorosis, scoliosis

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

Skin tumor cells are derived from neural crest cells (tumors of Schwann cells)

Question 3

Von Hippel Lindau disease

Answer 3

AD

Cavernous hemangiomas in skin, mucosa and organs

Bilateral renal cell carcinomas, hemangioblastoma (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerebellum
Pheochromocytomas
Cysts in kidney, liver, and pancreas

Mutated VHL tumor suppressor gene on chromosome 3 leads to constitutive expression of HIF and activation of angiogenic growth factors

Question 4

Neurofibromatosis type 2

Answer 4

Bilateral acoustic neuromas

AD

NF2 tumor suppressor gene encoding merlin on chromosome 22

Question 5

Li-Fraumeni syndrome

Answer 5

AD mutation of p53

Develop malignant tumors at young age (less than 45 y.o)

family history of malignancies less than 45

Most common: breast, brain, adrenal cortex, sarcomas and leukemia

Question 6

Sturge Weber Syndrome

Answer 6

Congenial non inherited developmental anomaly of NEURAL CREST derivatives (mesoderm/ectoderm)

Activating mutation of GNAQ gene

Affects small blood vessels leading to port-wine stain of face (in CN V1/V2 distribution)

Ipsilateral leptomeningeal angioma leads to seizures and epilepsy, intellectual disability
episcleral hemangioma leads to increased intraocular pressure and early onset glaucoma

Hemiplegia and skull tram track calcifications

Question 7

MEN 1

Answer 7

Chromosome 11-AD

Parathyroid tumors-hypercalcemia/chief cell hyperplasia
Pituitary tumors (prolactin or GH)-bitemorpal hemianopia
Pancreatic endocrine tumors: zollinger ellsion, insulinoma, VIPoma, glucaganoma

Presents as kidney stones and stomac ulcers

Question 8

MEN 2A

Answer 8

AD
Mutations in RET protooncogeen-neural crest cell origin

Medullar thyroid carcinoma (secretes calcitonin)
Pheochromocytoma
parathyroid hyperplasia

Question 9

MEN 2B

Answer 9

Mutations in RET protoncogene
Neural crest cell origin

Medullar thyroid carcinoma (secretes calcitonin)
Pheochromocytoma
Oral/intestinal ganglioneuromatosis (mucosal neuromas)

Associated with marfanoid habitus-long arm span and long fingers