Genetic/neuroendocrine Flashcards
Bilateral CN VIII schwannomas and multiple meningiomas. AD
NF 2
Chrom 22
Neurofibromas, optic nerve gliomas, Lisch nodules, café au lait spots
NF 1 (von Recklinghausen disease) Chrom 17
Cutaneous facial angiomas, leptomeningeal angiomas. V1 and V2 distributions of trigeminal nerve
Sturge-Weber syndrome
Tram-track calcifications
Kidney, liver, pancreatic cysts, cortical and subependymal hamartomas, rhabdomyoma, Ash-leaf spots, subependymal astrocytoma - AD
Tuberous sclerosis Renal angiomyolipomas (benign tumor w/blood vessels, smooth mm and fat) are also assoc w/TS
Congenital telangiectasias – AD
Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia)
Cerebellar hemangioblastoma, congenital cysts of kidneys, liver and pancreas - AD, pheo
Von Hippel-Lindau
Risk for bilateral RCC
How does prolactinoma cause amenorrhea, galactorrhea, and osteoporosis?
High prolactin suppresses GnRH from hypothal –> hypogonadism (low estrogen), anovulation, amenorrhea.
Sustained hyperprolactin –> low estrogen accelerates bone loss.
Fibrous dysplasia of the bone, endocrine problems, cafe-au-lait spots
McCune-Albright syndrome
Activating mutation in the G protein/CAMP/adenylate cyclase signaling pathway
Primary hyperparathyroidism (hypercalcemia/stones), pituitary tumors (periph vision loss), pancreatic tumors (includes ZE), angiofibromas and lipomas
MEN1
Medullary thyroid cancer (calcitonin), pheochromocytoma, mucosal neuromas/marfanoid habitus
MEN2B
Medullary thyroid cancer (calcitonin), pheochromocytoma, parathyroid hyperplasia
MEN2A
What does it mean when a drug has high lipophilicity?
high Vd, good penetration into CNS
Preferentially processed by the liver into more polar compounds
What is the MC secretory product of the pancreatic and duodenal endocrine lesions?
gastrin (can lead to peptic ulcers)
How can a carcinoid tumor cause pellagra?
The tumor secretes serotonin, depleting tryptophan (precursor to serotonin and niacin)
How does treatment of ZE syndrome with secretin cause increased serum gastrin?
Secretin inhibits gastrin release from stomach antrum, but stimulates gastrin secretion from a gastrinoma (pt with ZE).
Note: ZE patients typically have peptic ulcers (often beyond the duodenal bulb), abd pain/acid reflux, and diarrhea
Patient with ZE should be queried for a family history of what disorder?
MEN1 (pancreatic tumor - esp gastrinomas)
Primary hyperparathyroidism
Pituitary tumors
Differentiate localized vs metastatic carcinoid tumors
Localized to intestine - do not cause carcinoid synd bc secretory products are metabolized by the liver bf entering the systemic circ
Metastatic - release vasoactive substances that avoid first-pass metabolism –> flushing, diarrhea, bronchospasm
Small cell carcinoma can secrete what?
ACTH
Vasopression
Note: Squamous cell lung cancer can secrete PTHrP –> hypercalcemia)
Acoustic schwannomas are commonly located where in the brain? What other sx can develop due to the tumor?
Cerebellopontine angle
CN VIII - ipsilat SNHL/tinnitus and vertigo
CN VII - facial paresis
CN V - loss of facial sensation
Associated genes? Lynch synd FAP VHL Li-Fraumeni synd MEN1 MEN2
Lynch - MSH2, MLH1, MSH6, PMS2 FAP - APC VHL - VHL Li-Fraumeni - TP53 MEN1 - MEN1 MEN2 - RET
What genetic study can be done to diagnose Klinefelter?
Chromosomal analysis of lymphocytes
47XXY
What does unfavorable lyonization mean
Female patient who is a carrier of a X-linked disease gets the normal X chromosome inactivated –> displays phenotype. Hemizygous
Note: A chromosome in a diploid organism is hemizygous when only one copy is present.
Neck mass by carotid artery bifurcation that is positive for synaptophysin, chromogranin, and neuron-specific enolase. Dx?
Paraganglioma - rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen)
presence of multiple polyps in the colon together with tumors outside the colon.The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts
Gardner syndrome (familial colorectal polyposis) - AD mutation in the APC gene located in chromosome 5q21 (band q21 on chromosome 5). This is the same gene as is mutant in familial adenomatous polyposis (FAP), a more common disease that also predisposes to colon cancer.
infant with HTN, rapid eye movement, firm nodular midline abdominal mass and inc urine concentrations of homovanillic and vanillylmandelic acids. Dx?
Neuroblastoma - May cross midline. Assoc with N-Myc oncogene. Neural crest origin. common tumor of the adrenal medulla in children. HVA is a breakdown product of Dopamine in urine
Note: Wilms tumor is intrarenal
Female with excess skin on nape of neck and lymphedema of hands and feet. Chromosome analysis shows some cells with normal 46 XY and some cells with 45 X. What caused this cytogenetic abnormality?
Mosaic Turner’s syndrome and the mosaic trisomies result from nondisjunction during mitosis. In total monosomy/trisomies, the cause is nondisjunction during meiosis. Uniparental disomy is essentially only tested via the Prader-Willi and Angelman syndromes (chromosome 15).
Note: Excess skin = cystic hygroma
