Usmle Step 1 Genetic Diseases

Front 1

Prader-Willi Syndrome

Back 1

Chr: 15
Mx: Inactivation/deletion/uniparental disomy. Imprinting. Deletion of active paternal allele.
Hx: Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia.

Front 2

Angelman Syndrome

Back 2

Chr: 15
Mx: Inactivation/deletion/uniparental disomy. Imprinting. Deletion of active maternal allele.
Hx: Mental retardation, seizures, ataxia, inappropriate laughter ("happy puppet").

Front 3

Achondroplasia

Back 3

Gn: FGFR3
Mx: AD
Fx: Cell-signaling defect
Hx: Dwarfism, short limbs, head+trunk same size.
Assoc: Adv. paternal age.

Front 4

Autosomal-Dominant Polycystic Kidney Disease

Back 4

Chr: 16
Gn: APKD1 (point mutation)
Fx: Always bilateral massive kidney enlargement of kidneys due to multiple large cysts.
Onset: Adult
Hx: Flank pain, hematuria, HTN, progressive renal failure.
Assoc: Polycystic liver dz, berry aneurysms, mitral valve prolapse.

Front 5

Familial Adenomatous Polyposis

Back 5

Chr: 5
Gn: APC (deletion)
Mx: AD
Fx: Colon covered with adenomatous polyps after puberty, always progresses to colon CA unless resected.

Front 6

Familial Hypercholesterolemia (HLE IIA)

Back 6

Gn: LDLR
Mx: AD
Fx: Hetero - 300 mg/dL, homo - 700+.
Hx: Severe atherosclerotic dz early in life, tendon xanthomas (Achilles), MI < 20 y/o.

Front 7

Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu)

Back 7

Mx: AD
Fx: Inherited disorder of blood vessels
Hx: Telangiectasia, epistaxis, skin discolorations, AVMs.

Front 8

Hereditary Spherocytosis

Back 8

Mx: AD
Gn: Spectrin/Ankyrin defect
Fx: Spheroid erythrocytes
Hx: Hemolytic anemia, ↑MCHC
Tx: Splenectomy

Front 9

Huntington's Disease

Back 9

Chr: 4
Mx: AD, CAC-repeat
Hx: Depression, progressive dementia, choreiform movements, caudate atrophy, ↓GABA+ACh. S/S 20-50 y/o.

Front 10

Marfan's Syndrome

Back 10

Gen: Fibrillin
Mx: AD
Hx: Tall w/long extremities, pectus excavatum, hyperextensive joints, arachnodactyly, aortic cystic medial necrosis→aortic dissection, floppy mitral valve, lens subluxation.

Front 11

Multiple Endocrine Neoplasia 1

Back 11

Mx: AD
Hx: Pancreas+Parathyroid+Pituitary

Front 12

Multiple Endocrine Neoplasia 2

Back 12

Mx: AD
Gen: Ret
Hx: Thyroid+Medulla

Front 13

Neurofibromatosis 1 (von Recklinghausen's Disease)

Back 13

Chr: 17q
Mx: AD
Gen: NF1
Hx: Cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas).
Assoc: Skeletal disorders (e.g., scoliosis), optic gliomas, pheochromocytomas, ↑tumors.

Front 14

Neurofibromatosis 2

Back 14

Chr
Mx: AD
Gen: NF2
Hx: Bilateral acoustic neuroma, juvenile cataracts.

Front 15

Tuberous sclerosis

Back 15

Mx: AD (incomplete penetrance, variable presentation)
Hx: Facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical+retinal hamartomas, seizures, mental retardation, renal cysts+angiomyolipomas, cardiac rhabdomyomas, ↑astrocytomas.

Front 16

von Hippel-Lindau Disease

Back 16

Chr: 3p
Mx: AD, deletion.
Gen: VHL (tumor suppressor)
Fx: Constituitive HIF (transcription factor) expression, angiogenic growth factor activation.
Hx: Hemangioblastomas (retina/cerebellum/medulla), bilateral renal cell carcinoma, other tumors.

Front 17

Orotic Aciduria

Back 17

Mx: AR
Gn: Orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase
Fx: Orotic acid↛UMP
Hx: ↑orotic acid in urine, megaloblastic anemia (B12/folate no help), failure to thrive, no ↑NH4.
Tx: PO uridine

Front 18

Adenosine Deaminase Deficiency

Back 18

Gn: Adenosine deaminase
Fx: Purine salvage deficiency, no lymphocytes.
Hx: SCID.

Front 19

Lesch-Nyhan Syndrome

Back 19

Mx: XR
Gn: HGPRT
Fx: Purine salvage deficiency, Hypoxanthine↛IMP/Guanine↛GMP, ↑uric acid
Hx: Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis.

Front 20

I-Cell Disease

Back 20

Fx: Lysosomal storage disorder, can't add mannose-6-phosphate to proteins, lysosomal proteins exported outside cell, inclusions.
Hx: Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes. Fatal in childhood.

Front 21

Chediak-Higashi Syndrome

Back 21

Fx: Microtubule polymerization defect, ↓phagocytosis.
Hx: Recurrent pyogenic infections, partial albinism, peripheral neuropathy.

Front 22

Kartagener's Syndrome

Back 22

Gn: Dynein
Fx: Immotile cilia, dynein arm defect.
Hx: Male/female infertility, bronchiectasis, sinusitis.
Assoc: Situs inversus.

Front 23

Ehlers-Danlos Syndrome

Back 23

Gn: COL3
Fx: Faulty collagen synth.
Hx: Hyperextensible skin, easy bruising/bleeding, hypermobile joints.
Assoc: Joint disloc, berry aneurysms, organ rupture.

Front 24

Osteogenesis Imperfecta

Back 24

Mx: AD (common)
Gn: COL1
Hx: Multiple fractures w/minimal trauma, blue sclerae, hearing loss (abnormal middle-ear bones), dental imperfections.

Front 25

Alport's Syndrome

Back 25

Mx: XR
Gn: COL4
Hx: Progressive hereditary nephritis, deafness, ocular disturbances.

Front 26

Cystic Fibrosis

Back 26

Chr: 7
Mx: AR
Gn: CFTR (d508F)→abnormal folding→degradation before surface
Fx: CFTR is active chloride pump, secretes in lungs, reabsorbs from sweat. Secreton of abnormally thick mucus (lungs, pancreas, liver).
Hx: Recurrent pulm infections (Pseudomonas, S. aureus), chronic bronchitis, bronchiectasis, pancreatic insuf. (malabsorption, steatorrhea), meconium ileus, male infertility (vas deferens absent), ADEK-deficiency.
Assoc: Sweat test
Tx: N-acetylcysteine to loosen plugs.

Front 27

Duchenne's Muscular Dystrophy

Back 27

Mx: XR
Gn: DMD (frameshift), high rate of spontaneous mutation.
Fx: Accelerated muscle breakdown (dystrophin anchors fibers).
Hx: Progressive weakness, start in pelvic girdle, goes up. Pseudohypertrophy of calf muscles (fibrofatty replacement), cardiac myopathy. Onset < 5 y/o. Need arms to stand (Gowers' maneuver).
Dx: ↑CPK, biopsy.

Front 28

Becker's Muscular Dystrophy

Back 28

Mx: XR
Gn: DMD
Hx: Less severe than Duchenne's. Onset in adol/early adult. Hx: Progressive weakness, start in pelvic girdle, goes up. Pseudohypertrophy of calf muscles (fibrofatty replacement), cardiac myopathy. Need arms to stand (Gowers' maneuver).
Dx: ↑CPK, biopsy.

Front 29

Fragile X Syndrome

Back 29

Mx: XR
Gn: FMR1 (CGG repeat)
Hx: Retardation (2nd after Down), macro-orchidism, long face w/large jaw, large everted ears, autism, mitral valve prolapse.
Assoc: Chromosomal breakage

Front 30

Down's Syndrome

Back 30

Mx: Trisomy 21
Hx: Retardation, flat facies, epicanthal folds, simian crease, 1st 2 toes gap, duodenal atresia, septum primum ASD.
Assoc: ALL, Alzheimer's.
Dx: Pregnancy quad screen - ↓AFP, ↓estriol, ↑b-hCG, ↑inhibin A. Nuchal translucency in usound.

Front 31

Edwards' Syndrome

Back 31

Mx: Trisomy 18
Hx: Severe retardation, micrognathia, clenched hands, heart dz.

Front 32

Patau's Syndrome

Back 32

Mx: Trisomy 13
Hx: Cleft lip/palate, holoprosencephaly, polydactyly, heart dz.

Front 33

Cri-du-chat Syndrome

Back 33

Mx: 5p-
Hx: Microcephaly, retardation, high-pitched cry, epicanthal folds, cardiac problems.

Front 34

Williams Syndrome

Back 34

Mx: 7q- (esp. elastin)
Hx: Elfin facies, retardation, ↑[Ca] (↑vitD sens), good talker, very friendly, cardiovascular problems.

Front 35

DiGeorge Syndrome

Back 35

Mx: 22q11-
Fx: CATCH-22: Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia (parathyroid aplasia). Aberrant development of 3rd/4th branchial pouches.
Hx: Thymic, parathyroid, cardiac defects.

Front 36

Velocardiofacial Syndrome

Back 36

Mx: 22q11-
Fx: CATCH-22: Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia (parathyroid aplasia). Aberrant development of 3rd/4th branchial pouches.
Hx: Palate, facial, cardiac defects.

Front 37

G6PD Deficiency

Back 37

Mx: XR
Fx: ↓NADPH→↓Glutathione→Hemolysis.
Hx: Blacks, malarial resistance
Assoc: Heinz bodies (oxidized hemoglobin), Bite cells (phagocytic removal of Heinz bodies)