Disorders

Front 1

Pheochromocytoma

Back 1

Hyperplasia of adrenal medullary tissue resulting in a catecholamine-secreting tumor. Symptoms include hypertension, tachycardia, sweating, tremor, and glucose intolerance. Increased urinary catecholamine levels for diagnosis. Usually affects only one adrenal gland, which is surgically removed.

Front 2

Adrenal Insufficiency

Back 2

Primary: Destruction of adrenal glands, High K+, High CRH/High ACTH/Low cortisol, Acidosis.
Secondary: Destruction of pituitary corticotroph cells; subsequent atrophy of fasciculata and reticularis. Low ACTH/Low cortisol/High CRH.
Weakness, lethargy, fatigue, nausea, vomiting, diarrhea, low BP, low Na+, mild anemia, increase in eosinophils.
Also can be caused by glucocorticoid resistance.

Front 3

Addison's Disease

Back 3

Autoimmune destruction of adrenal glands -> 1` adrenal insufficiency.
Low cortisol/High CRH/High ACTH. Sx: hyperpigmentation from high ACTH, weakness/fatigue, weight loss, GI disturbances. HypoNa+, hypoglycemia, and hyperK+.

Front 4

21 alpha-Hydroxylase Deficiency

Back 4

Lack of enzyme involved in production of aldosterone and corticosterone (converts 11-deoxycorticosterone to corticosterone). Leads to inadequate production of gluco- and mineralocorticoids. Hypotension and dehydration from salt loss; hypoglycemia due to cortisol deficiency. ACTH increases->adrenal gland hypertrophy and increased androgens. Effects referred to as virilizing congenital adreanl hyperplasia.

Front 5

Cushing's Syndrome

Back 5

Glucocorticoid excess resulting in central obesity w/ striae, acne, hyperpigmentation of skin, hirsutism, hypertension, muscle weakness, hyperglycemia, polyuria, "moon face". Two types: (1) ACTH dependent (Cushing's disease) is due to excessive pituitary ACTH secretion from a pituitary tumor, or possibly ectopic ACTH or CRH. (2) ACTH independent from adrenal adenoma/carcinoma/hyperplasia or exogenous steroids resulting in suppressed ACTH and CRH. Screening test is dexamethasone suppression test (inhibits ACTH meaning plasma [glucocorticoid] should be low). Increased adrenal androgens result in early 2` sex characteristics in men, but excess cortisol inhibits LH thus decreasing testosterone. Virilization, hirsutism, and acne in women.

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DiGeorge Syndrome

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AKA Velocardiofacial (VCFS) syndrome, aka 22q11.2 deletion syndrome. Autosomal dominant inheritance, but ~93% have de novo deletion. CATCH 22: Cardiac abnormalities, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia. Tetralogy of Fallot and persistence of truncus arteriosus, incomplete development of 3rd and 4th branchial arches -> parathyroid and thyroid hypoplasia, etc. From haploinsufficiency of TBX1 encoding a TF for development of the pharyngeal system.

Front 7

Tetralogy of Fallot

Back 7

Pulmonary stenosis and ventricular septal defect leading to overriding aorta and hypertrophy of the right ventricle.
Most cases are isolated, but is ass'd w/ alcohol abuse during pregnancy.

Front 8

Rickets/Osteomalacia

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Dietary deficiency of Vitamin D characterized by hypocalcemia and skeletal abnormalities (bowed legs). Chronic renal failure (involves decreased 1 alpha-hydroxylase) also leads to similarities to rickets.

Front 9

Osteoporosis

Back 9

Decreased bone density. Postmenopausal women are very prone to this due to loss of estradiol. Glucocorticoid excess can also lead to this. Can be treated w/ estrogen, calcitonin, bisphosphonates.

Front 10

Cystic Fibrosis

Back 10

Autosomal recessive disorder involving mutation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene on chromosome 7, which normal encodes a Cl- channel. Cl- builds up in cytoplasm, causing influx of Na+ -> this leads to thick mucus buildup in lungs, pancreatic insufficiency, and CBAVD in men. Cl- sweat test is the gold standard diagnostic test. Many mutations have been identified, being grouped into 5 classes, with the deltaF508 (Class II) mutation being the most common.

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Fragile X Syndrome

Back 11

X-linked disorder involving TriNT(CGG) repeat expansion in the FMR1 gene. Premutation repeat number b/w 60-200 is ass'd w/ FXTAS and FMR1-releated POV from decrease in FMRP resulting in increase in transcription of FMR1. FMR1 mRNA over-production and buildup leads to mRNA toxicity in cell by sequestering RNA binding proteins needed for synthesis of other mRNAs. Mutation repeat number above 200 leads to hypermethylation of the FMR1 gene preventing transcription and leading to characteristic uncondensed 'fragile site'. Phenotype includes mental retardation, protuberant ears, large head. Pre-to-full mutation can be passed on maternally, but not paternally.

Front 12

Tay Sachs Disease

Back 12

Autosomal recessive disorder of ganglioside catabolism caused by a deficiency of hexosaminidase A. HexA is a lysosomal enzyme encoded in HEXA gene that degrades GM2 gangliosides. Mutation in HEXA leads to accumulation of gangliosides in the lysosome, leading to neuropathy and death usually by age 3.

Front 13

Beckwith-Wiedemann Syndrome

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Growth regulation disorder w/ somatic overgrowth and predisposition to embryonic tumors. Sx include macroglossia, macrosomia, omphalocele, gigantism, visceromegaly, Wilm's Tumor, and hypoglycemia. Can result from excess of paternal or loss of maternal (or both) genes on 11p15 (ie paternal uniparental disomy).

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Prader-Willi Syndrome

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Involves one of 3 mechanisms: Chromosomal deletion of paternal PWS region, maternal uniparental disomy, or imprinting center defect in father. All mech's involve more mom expression. Features include hypotonia at birth, mental retardation, compulsive childhood hyperphagia, obesity, and hypogonadism.

Front 15

Angelmann Syndrome

Back 15

Involves 1 of 4 mechanisms: Deletion of maternal PWS region, parental uniparental disomy of chromosome 15, imprinting center defect in mother, or mutation in the maternal UBE3A gene (AS gene). All mech's involve more dad expression. Features include developmental delay, speech impairment, ataxia, constantly happy demeanor.

Front 16

Down Syndrome

Back 16

Trisomy 21, this is the most commmon chromosome disorder and most common genetic cause of mental retardation. Sx: short stature, single palmar crease, flat occiput, high risk of congenital heart disorders, GI disorders. Higher maternal age is a major risk factor. Can be caused by an inherited Robertsonian translocation b/w chromosome 21q and the q of usually 14 or 22 (ass'd w/ high risk of recurrence). Quad test is used for screening for Downs in 2nd trimester (low AFP, low UE3, high hCG, and high inhibin A). 1st trimester screening includes beta-hCG, PAPP-A, and nuchal translucency.

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Huntington Disease

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Front 18

Chronic Myelogenous Leukemia

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Due to reciprocal translocation in which proto-oncogene ABL, a tyrosine kinase, moves from it's normal position on 9q to the Breakpoint Cluster Region gene on 22q. Fusion protein has more tyrosine kinase activity than ABL alone, and causes proliferation thru constitutive Ras expression or decreased apoptosis thru continuous Bad phosphorylation via PI3K and Akt(PKB), leading to upregulation of anti-apoptotic BCL-2. Also reduced adhesion to fibronectin, thus impeding wound healing process. Disease has a chronic/stable phase, accelerated phase, and a blast crisis phase. Sx include fatigue, weight loss, hepato/splenomegaly, nausea, headaches, night sweats. Treated w/ imatinib.

Front 19

Retinoblastoma

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Results from loss of function of both alleles of RB1, a TSG encoding a phosphoprotein that controls cell cycle progression from G1 to S by binding to and inactivating TFs, such as E2F (when hyperphosphorylated Rb1 releases TFs and allows G1-S transition). LOF follows the 2-hit model, in which pt either inherits a mutated gene and then 2nd gene mutates, or is extremely unlucky and has one random somatic mutation followed by another in a cell containing the first.

Front 20

Familial Adenomatous Polyposis (FAP)

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Autosomal dominant disorder involving numerous colorectal adenomas developed by teenage years. Signs include a 100's of polyps (sp. stomach and duodenal polyps). Main gene mutated is the Adenomatous Polyposis Coli Gene (APC), whihc is a TSG that binds and degrades beta-catenin. W/o FAP, beta-catenin accumulates and translocates to the nucleus, where it acts as a TF for proteins involved in cell proliferation.

Front 21

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)/Lynch Syndrome

Back 21

An autosomal dominant disease it is the most common hereditary form of colon cancer. Results from germline mutation of a DNA repair gene followed by 2nd-hit (caretaker genes MLH1, MSH2, or MSH). Loss of caretaker gene leads to frameshift mutations in microsatellite sequence tracts. In HNPCC it leads to mutations in TGF-beta type II TSG, which is a serine-threonine kinase that inhibits growth and induces apoptosis in epithelial cells. Most commonly found in the right colon.

Front 22

Klinefelter's Syndrome

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XXY syndrome - most common sex chromosome disorder in males involving hypogonadism (low testosterone, but high LH/FSH) and reduced fertility. Also microorchidism and incomplete development of 2ry sexual characteristics.

Front 23

Kallman Syndrome

Back 23

Disordered migration of GnRH cells during embryologic development leads to a lack of GnRH neurons, thus no GnRH pulse, lack of LH/FSH, and absence of secondary sex characteristics. Also, anosmia and amenorrhea in females. Treated w/ pulsatile exogenous GnRH.

Front 24

5alpha-reductase deficiency

Back 24

Autosomal recessive gene mutation leads to inability of body to convert testosterone to DHT leads to inhibition of 2ndry sex characteristic development in males. Common cause of male pseudohermaphroditism in which males have a normal karyotype and Wolffian structures (ie, Mullerian regression occurs), but ambiguous external genitalia or female genitalia. Spermatogenesis, muscle mass, libido and deepening of voice still occur, but less facial/body hair, no acne, and hypospadias or micropenis may occur.

Front 25

Androgen Insensitivity Syndrome (AIS)

Back 25

X-linked recessive mutation in the androgen receptor gene (on X chromosome) and is a common cause of male pseudohermaphroditism in which there are normal levels of testosterone and DHT, but androgen receptors are absent or defective. Wolffian ducts degenerate, female external genitalia develop, but normal MIS levels still suppress Mullerian development. Usually short vagina, normal testes, breast development at puberty due to aromatase making estrogen from testosterone, and primary amenorrhea.

Front 26

Turner Syndrome

Back 26

Most common form of gonadal dysgenesis (occurs only in women). Involves 45 XO karyotype resulting in immature ovaries resulting in high GnRH/FSH/LH b/c of very low estrogen. Pt. usually has short stature, primary amenorrhea, sexual infantilism, webbed neck.

Front 27

SRY Gene Mutations

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Mostly caused by translocation of SRY gene b/w X and Y chromosomes resulting in internal and external female sexual development (b/c no MIS). Streak gonads, no 2ndry sex characteristics at puberty, primary ammenorhea. Gonadectomy performed to avoid neoplasia.

Front 28

Pre-eclampsia

Back 28

Combination of pregnancy-induced hypertension and proteinuria. Most common dangerous pregnancy complication and primarily a disease of 1st pregnancies and pregnancies after a change in sexual partner. Caused by placenta releasing factors that increase blood pressure to improve flow to placenta, likely as a strategy when there are inadequate nutrients for fetus, due to poor placental invasion and remodeling of spiral arteries.

Front 29

Pendred Syndrome

Back 29

Combo of congenital hypothyroidism and acoustic-nerve deafness; caused by mutation in the gene encoding the pendrin protein that transports iodide from the follicular cell cytosol to the lumen

Front 30

Hashimoto's Thyroiditis

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Hypothyroidism caused by autoimmune destruction of the thyroid; presence of autoantibodies against the thyroid follicular cells, thyroglobulin, TPO, and TSH receptors. Sx: painless enlargement of thyroid; high TSH, low T3/T4. Initial thyroid destruction causes an acute flood of T4/T3 (hyper) followed by hypo.

Front 31

Grave's Disease

Back 31

Hyperthyroidism caused by thyroid stimulating immunoglobulin (TSI) that binds to and activates the TSH receptor. Sx: include those of hyperthyroidism, and characteristic "stare", and possibly pretibial myxedema.

Front 32

Lapatinib

Back 32

Another her2/neu inhibitor that is small enough to cross blood-brain barrier and also binds intracellular portion of receptor. Less resistance to this drug.