High-yield associations Flashcards
VHL gene (deletion on chromosome 3p) tumor suppressor gene
Sporadic renal cell carcinoma
Autosomal dominant Von Hippel-Lindau (cerebellar and retinal hemangioblastoma, clear cell renal carcinoma, pheochromocytoma)
C-MYC (chromosome 8) oncogene
Burkitt lymphoma
Diffuse large B cell lymphoma
NF-1 (chromosome 17) tumor suppressor gene
Neurofibromatosis type 1 (AKA von Recklinghausen disase)
Autosomal dominant mutation of NF1 that encodes protein neurofibromin
Characterized by cutaneous neurofibromas (fleshy, dome-shaped or pedunculated made of Schwann cells), cafe-au-lait spots, Lisch nodules (hamartoma of the iris), sphenoid dysplasia, congenital pseudoarthrosis, scoliosis
RB (chromosome 13) tumor suppressor gene
Retinoblastoma
Osteosarcoma
WT-1 (chromosome 11) tumor suppressor gene
Wilms tumor
45, XO
Turner syndrome
Low-set ears, webbed neck, wide-spaced nipples, cardiac defects (e.g. coarctation of the aorta, bicuspid aortic valve), narrow, high arched palate, low hairline, short stature, broad chest (“shield chest”), primary amenorrhea (streak ovaries), horseshoe kidney, intellectual disability, lymphatic outflow abnormalities (lymphedema, cystic hygroma)
46, XX, del(22)(q11)
DiGeorge syndrome
Hypertelorism, micrognathia, cleft palate, cardiac defects (e.g. interrupted aortic arch, Tetrology of Fallot)
47, XX, +18
Edwards syndrome
Low-set ears, micrognathia, clenched hands with overlapping fingers, hypertonia, cardiac defects, rocker bottom feet, omphalocele
47, XX, +21
46, XX, t(14;21) - Robertsonian translocation
Down Syndrome
Epicanthal folds, upslanting palpebral fissures, protruding tongue, excessive skin at the nape of the neck, below average birth weight and length, hypotonia, weak Moro reflex, cardiac defects (e.g. VSD), duodenal atresia (double bubble sign)
Fetal alcohol syndrome
Short palpebral fissures, smooth philtrum, thin vermillion border
Teratogenic effects of phenytoin
Neural tube defects, orofacial clefts, microcephaly, nail or digit hypoplasia
Teratogenic effects of lithium
Ebstein anomaly (ASD, atrialized right ventricle, malformed tricuspid valve), nephrogenic diabetes insipidus, hypothyroidism
Teratogenic effects of valproate
Neural tube defects
Teratogenic effects of isotretinoin
Microcephaly, thymic hypoplasia, small ears, hydrocephalus
Teratogenic effects of methotrexate
Limb and craniofacial abnormalities, neural tube defects, abortion
Teratogenic effects of ACE inhibitors
Renal dysgenesis, oligohydramnios
Teratogenic effects of warfarin
Nasal hypoplasia, stippled epiphysis
Teratogenic effects of tetracyclines
Teeth staining
Amoxicillin is the first-line for Lyme disease during pregnancy
Teratogenic effects of chloramphenicol
“Gray baby” syndrome
Teratogenic effects of TMP/SMX
Neural tube defects
Teratogenic effects of aminoglycosides
Ototoxicity, vetibulotoxicity
Arachnodactyly, scoliosis, aortic root dilation
Marfan syndrome
Inherited defect of the extracellular matrix protein fibrillin (FBN1 gene) responsible for the production and maintenance of elastic fibers
Often exhibits variable expressivity
Other symptoms: tall, thin body habitus, hypermobile joints, aortic dissection, peumothorax
Macroorchidism, large jaw, intellectual disability
Fragile X syndrome
Expansion of trinucleotide repeats on FMR1 gene on the long arm of the X chromosome –> FMR1 hypermethylation –> prevention of transcription
May also see long and narrow face, prominent forehead and chin, hyperlaxity of hand joints
Short stature, hypotonia, intellectual disability, obesity, hyperphagia, hypogonadism
Prader-Willi
Microdeletion of paternal chromosome 15 or maternal uniparental disomy
47, XXY
Kleinfelter syndrome
Tall stature, small, firm testes, azoospermia (primary hypogonadism), gynecomastia, mild intellectual disability
Labs: ↓ testosterone –> ↑ GnRH –> ↑ LH/FSH –> ↑ estradiol
Primary ciliary dyskinesia
Autosomal recessive dynein arm defect impairs normal ciliary motion and mucociliary clearance
Chronic sinusitis, nasal polyps, bronchiectasis, digital clubbing, situs inversus, infertility due to immotile spermatozoa
Dx: low nasal nitric oxide levels, bronchoscopy and electron microscopic visualization of ciliary abnormalities, genetic testing
Situs inversus + chronic sinusitis + bronchiectasis = Kartagener syndrome
Cystic fibrosis
Mutation of CFTR gene
Chronic sinusitis, nasal polyps, bronchiectasis, digital clubbing, pancreatic insufficiency, infertility due to absent vas deferens, failure to thrive
Dx: elevated sweat chloride levels, abnormal nasal transepithelial potential difference, genetic testing
Krunkenberg tumor
Primary gastric cancer that has metastasized to the ovary via lymphatics
Histology shows mucin-filled signet ring cells.
Which HPV strains are associated with cervical cancer?
16, 18
1, 4 (skin warts)
6, 11 (genital warts/condylomata acuminata)
Which tumors have psammoma bodies?
Papillary carcinoma of the thyroid
Serous cystadenocarcinoma of the ovaries
Mesothelioma
Meningioma
Achondroplasia
Gain-of-function point mutation of FGFR3 gene –> inhibits cartilage proliferation, esp of long bones –> shortened proximal long bones (humerus, femur), shortened digits
Also midface hypoplasia, frontal bossing, trident hand (space between 3rd and 4th digit), bowing of tibia (genu varum)
Osteogenesis imperfecta
Mutations in COL1A1 or COL1A2 genes –> improper type 1 collagen
May manifest with premature osteoporosis, short stature, scoliosis, blue sclerae, hearing loss, increased skin and ligament laxity, easy bruisabiity, opalescent teeth
BRCA 1/2 tumor suppressor
DNA repair genes
Breast and ovarian cancer
ATP7B gene mutation (chromosome 13)
Wilson disease (autosomal recessive) defect in hepatic copper excretion and failure of copper to enter circulation as ceruloplamin
May manifest with hemolytic anemia, parkinsonian symptoms, asterixis, dementia, chorea, cirrhosis, hepatocellular carcinoma, Kayser-Fleischer rings
Dx: ↓ ceruloplasmin
Tx: D-penicillamine, trientine (copper chelators)
HFE gene mutation
Mutation of HFE gene product –> reduced synthesis of hepcidin (encoded by HAMP gene) –> ferroportin remains active –> increased efflux of iron from enterocytes –> iron deposition and free radical damage (hemochromatosis)
Carcioembryonic antigen (CEA)
Tumor marker for colorectal carcinoma
Useful for detecting residual disease and recurrence
Alpha fetoprotein (AFP)
Tumor marker for hepatocellular carcinoma and germ cell tumors (e.g. endodermal sinus/yolk sac tumors)
Elevated AFP in maternal serum may also indicate gastroschisis
CA 19-9
Tumor marker for pancreatic cancer
CA 125
Tumor marker for ovarian epithelial cancers
Human chorionic gonadotropin
Tumor marker for choriocarcinoma
Treatment for arsenic poisoning
Dimercaprol
Arsenic can be found in pesticides/insecticides and cause garlicky breath and QTc prolongation
Treatment for acute lead poisoning
CaNa2EDTA
Treatment for iron overdose
Deferoxamine
Treatment for cyanide poisoning
Hydroxycobalamin
Treatment for methemeglobinemia
Methylene blue
Mutation of APC tumor suppressor gene
First mutation in the adenoma-carcinoma sequence of colorectal carcinoma
Hereditary mutation in Familial Adenomatous Polyposis
Mutation of TP53 tumor suppressor gene
Last mutation in the adenoma-carcinoma sequence of colorectal carcinoma
Hereditary mutation in Li-Fraumeni syndrome (breast cancer, sarcomas, brain tumors, adrenocortical carcinoma, leukemia)
Mutation of MEN1 tumor suppressor gene
Associated with Multiple Endocrine Neoplasia type I (parathyroid adenomas, pituitary adenomas, pancreatic adenomas)
Mutation in RET oncogene
Associated with Multiple Endocrine Neoplasia type II = medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia (IIA) or glioblastomas (IIB)
Mutations in DNA mismatch repair genes MSH2, MLH1, MSH6, PMS2 (tumor suppressors)
Associated with Lynch syndrome (colorectal cancer, endometrial cancer, ovarian cancer)
S-100
Expressed in neural crest cells
Tumor marker for melanoma, neural tumors, schwannomas, Langerhans cell histiocytosis)
BRAF protein kinase mutation
Melanoma
Hilar lymdphadenopathy, hypercalcemia, elevated ACE
Sarcoidosis
Often seen in young female African Americans
Elevated calcium from PTH-independent formation of 1,25-OH vitamin D by activated macrophages
Smoking history, lung nodules, hypercalcemia
Paraneoplastic syndrome from lung cancer
Release of PTH-related peptide
Does not upregulate 1-alpha hydroxylase like PTH so no effect on 1,25-OH vitamin D
BMPR2 gene mutation
Familial pulmonary arterial hypertension
Mutation causes proliferation of vascular smooth muscle
Poor prognosis
Genetic disease associated with bilateral acoustic neuromas
Neurofibromatosis type II
Autosomal dominant mutation in NF2 (chromosome 22) that encodes protein merli
Hypoplasia of the mandibular and zygomatic bones, hearing loss
Treacher-Collins syndrome
Abnormal development of the first and second pharyngeal arches
“Floppy baby” with hypotonia and tongue fasciculations
Spinal muscular atrophy (Werdnig-Hoffman disease)
Mutation in survival motor neuron gene (SMN1) which encodes a protein involved in assembly of snRNPs in LMN –> defective snRNPs results in impaired splicesome function and congenital degeneration of the anterior horns of the spinal cord –> LMN signs
N-myc
Neuroblastoma
Dystonia, choreoathetosis, self-mutilation, hyperuricemia –> gout, intellectual disability
Lesch-Nyhan syndrome
X-linked recessive deficiency of hypoxanthine-guanine phorphoribosyltransferase (purine salvage pathway)
Tx: allopurinol or febuxostat (2nd line)
Gait ataxia, spastic muscle weakness, loss of position and vibration sensation, kyphoscoliosis, pes cavus (high foot arches), diabetes, hypertrophic cardiomyopathy
Friedreich ataxia
Autosomal recessive trinucleotide repeat (GAA) mutation of FXN gene –> decreased expression leads to decreased mitochondrial energy production and increased oxidative stress –> degeneration of peripheral neural tracts
Distal leg weakness/atrophy, sensory deficits, pes cavus, kyphoscoliosis, not hypertrophic cardiomyopathy
Charcot-Marie-Tooth disease
Autosomal dominant –> demyelination of peripheral nerves
Myotonia (abnormally slow relaxation of muscles), cataracts, frontal balding, gonadal atrophy
Myotonic dystrophy
Autosomal dominant abnormal trinucleotide repeat expansion (CTG) that codes for a myotonia-protein kinase
Atrophy of type 1 muscle fibers
Subdural hematomas, retinal hemorrhages, posterior rib fractures
Abusive head trauma (“shaken baby syndrome”)
Black urine, blue-black discoloration of cartilage and skin
Alkaptonuria
Autosomal recessive defect in homogentistic acid dioxygenase
Also characterized by osteoarthropathy
CA-19-9
Tumor marker for pancreatic adenocarcinoma
TRAP
Tumor marker for hairy cell leukemia (B cells)
Inappropriate laughter (“happy puppet”), seizures, ataxia, severe intellectual disability
Angelman syndrome
Microdeletion of maternal gene or paternal uniparental disomy
Family history of early artherosclerotic disease and cardiovascular disease, tendon xanthomas (esp. Achilles)
Familial hypercholesterolemia
Defective or absent LDL receptor
