Usmle Step 1 Fa Biochemistry-Genetic Diseases

Front 1

Prader Willi syndrome
(a) defect
(b) clinical findings

Back 1

(a) Inactivation or deletion of paternal chromosome 15
(b) Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

Front 2

AngelMan's Syndrome
(a) defect
(b) clinical findings

Back 2

(a) inactivation or deletion of maternal chromosome 15
(b) Mental retardation, seizures, ataxia, inappropriate laughter ("happy puppet")

Front 3

Hypophosphatemic rickets
(a) defect
(b) mode of inheritance
(c) clinical findings

Back 3

(a) aka vitD resistant rickets; increased phosphate wasting in the proximal tubule
(b) X linked dominant
(c) Rickets like presentation

Front 4

Leder's hereditary optic neuropathy
(a) mode of inheritance
(b) effect of disease
(c) clinical findings

Back 4

(a) mitochondrial inheritence
(b) degeneration of retinal ganglion cells and axons
(c) acute loss of central vision

Front 5

Achondroplasia
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) clinical associations

Back 5

(a) cell signaling defect of FGFR3
(b) AD
(c) dwarfism; short limbs but head and trunk are normal sized
(d) associated with advanced paternal age

Front 6

Adult Polycystic Kidney Disease (APKD)
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) clinical associations

Back 6

(a) 90% due to muts in APKD1 (c16)
(b) AD (note that infantile form is AR)
(c) Always b ilateral; massive enlargement of kidneys due to large cysts.
(d) polycystic liver disease, berry aneurysms, mitral valve prolapse.

Front 7

Familial adenomatous polyposis
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) clinical associations

Back 7

(a) depetion on c5 (APC gene)
(b) AD
(c) colon becomes covered w/adenomatous polyps after puberty.
(d) progresses to colon cancer unless resected.

Front 8

Familial hypercholesterolemia (hyperlipidemia type IIA)
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) clinical associations

Back 8

(a) defective or absent LDL receptor
(b) AD
(c) Elevated LDL. Heteros have cholesterol ~300mg/dl. Homos (v. rare) have cholesteral ~700mg/dl (severe atherosclerosis early in life and tendon xanthomas-classically Achilles).
(d) MI may develop before age 20

Front 9

Hereditary hemorrhagic telangiectasia aka Osler-Weber-Rendu
(a) defect
(b) mode of inheritance
(c) clinical findings

Back 9

(a) inherited disorder of blood vessels
(b) AD
(c) Telangiectasia, recurrent epistaxis, skin discolorations, AVM's

Front 10

Hereditary spherocytosis
(a) defect
(b) mode of inheritance
(c) clinical findings
(d)treatment

Back 10

(a) Spectrin or ankyrin defect
(b) AD
(c) autoimmune hemolytic anemia; incr MCHC
(d) Splenectomy is curative

Front 11

Huntington's disease
(a) defect
(b) mode of inheritance
(c) clinical findings

Back 11

(a) Defect in hungtintin gene on c4. (trinucleotide repeat disorder) CAGn
(b) AD
(c) depression, progressive dementia choreiform movements, caudate atrophy, decr GABA and Ach in brain. Manifests b/w 20-50YO.

Front 12

Marfan's syndrome
(a) defect
(b) mode of inheritance
(c) clinical findings

Back 12

(a) fibrilling gene mutation-->CT disorder affectin heart, skeleton, and eyes
(b)AD
(c) Tall w/long extremities, pectus excavatum, hyperextensive joints, and long, tapering fingers and toes (arachnodactyly); cystic medial necrosis of aorta-->aortic incompetence and dissecting aortic aneurysms; floppy mitral valve. Subluxation of lenses.

Front 13

Multiple endocrine neoplasias (MEN)
(a) defect
(b) mode of inheritance
(c) clinical associations

Back 13

(a) Distinct syndromes I, II, III (MEN I, II assoc w/ ret muts)
(b)AD
(c) familial tumors of endocrine glands (pancreas, parathyroid, pit, thyroid, and adrenal medulla

Front 14

Neurofibromatosis type I (von Recklinghausen's disease)
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) clinical associations

Back 14

(a) long arm of c17
(b) AD
(c) Café au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas)
(d) skeletal disorders (scoliosis), optic pathway gliomas, pheochromocytoma, and incr tumor susceptibility

Front 15

Neurofibromatosis type II
(a) defect
(b) mode of inheritance
(c) clinical findings

Back 15

(a) NF2 gene on c22
(b) AD
(c) bilateral acoustic neuroma; juvenile cataracts

Front 16

Tuberous sclerosis
(a) defect
(b) mode of inheritance
(c) clinical findings

Back 16

(a) n/a incomplete penetrance, variable penetration
(b) AD
(c) Facial lesions (adenoma sebaceum), hypopigmented spots on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts and renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas.

Front 17

vonHippel-Lindau
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) clinical associations

Back 17

(a) Assoc w/deletion of VHL gene (tumor suppressor) on C3; constitutive expression of HIG and activation of angiogenic GF's
(b) AD
(c) Hemangioblastomas of retina/cerebellum/medulla.
(d) Half will develop multiple bilateral RCC and other tumors.

Front 18

Mode of inheritance : albinism

Back 18

AR

Front 19

Mode of inheritance : alpha 1 antitrypsin

Back 19

AR

Front 20

Mode of inheritance : ARPKD aka infantile polycystic kidney disease

Back 20

AR

Front 21

Mode of inheritance : glycogen storage disease

Back 21

AR

Front 22

Mode of inheritance : cystic fibrosis

Back 22

AR

Front 23

Mode of inheritance : hemochromatosis

Back 23

AR

Front 24

Mode of inheritance : mucopolysaccharidosis (except Hunter's)

Back 24

AR

Front 25

Mode of inheritance : phenylketonuria

Back 25

AR

Front 26

Mode of inheritance : sickle cell anemias

Back 26

AR

Front 27

Mode of inheritance : sphingolipidoses (except Fabry's)

Back 27

AR

Front 28

Mode of inheritence: thalassemias

Back 28

AR

Front 29

Cystic fibrosis:
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) clinical associations
(e) diagnosis
(f) treatment

Back 29

(a) CFTR gene on c7 resulting in defect Cl- channel; normally actively secretes Cl-in lungs/GI and reabsorbs Cl- from sweat. Mutation results in abnormally thick mucus that plugs lungs, pancreas, and liver.
(b) AR
(c) Recurrent pulmonary infx (pseudomonas, and S. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), meconium ileus in newborns.
(d) Infertility in males (bilateral absence of vas deferens). Fat soluble vitamin deficiencies. Can present as failure to thrive in infancy.
(e) Incr Cl- in sweat test
(f) N-acetylcysteine to loosen mucous plugs (cleaves disulfide bonds of glycoproteins)

Front 30

X linked recessive disorders
Be Wise, Fool's GOLD Heeds False Hope

Back 30

Bruton's agammaglobulinemia
Wiskott-Aldrich syndrome
Fragile X
G6PD deficiency
Ocular albinism
Lesch-Nyhan syndrome
Duchenne's (and Becker's) muscular dystrophy
Hemophilia A and B
Fabry's disease
Hunter's syndrome

Front 31

Duchenne's Muscular Dystrophy
(a) defect
(b) mode of inheritance
(c) clinical findings
(d) diagnosis

Back 31

(a) Frame shift mutation-->deletion of dystrophin gene-->accelerated muscle breakdown
(b) X linked
(c) weakness in pelvic girdle muscles moving superiorioly. Pseudohypertrophy of calves; cardiac myopathy. Use of Gower's maneuver. Onset before age 5.
(d) increased CPK and muscle biopsy

Front 32

Becker's muscular dystrophy
(a) defect
(b) mode of inheritence
(c) clinical findings

Back 32

(a) mutated dystrophin gene
(b) x linked
(c) less severe than duchenne's w/presentation in adolescence or early adulthood

Front 33

Fragile x syndrome
(a) defect
(b) mode of inheritance
(c) clinical findings

Back 33

(a) Defect in methylation and expression of FMR1 gene; assoc w/chromosomal breakage. Trinucleotide repeat disorder (CGG)n.
(b) Xlinked
(c) 2nd MCC of mental retardation; macroorchidism, long face with large jaw, large everted ears, autism.

Front 34

Name the trinucleotide expansion repeat diseases (w/subsequent expansion defect)

Back 34

Huntington's (CAG)
Myotonic dystrophy (CTG)
Fragile X syndrome (CGG)
Freidrich's ataxia (GAA)

Front 35

Down syndrome
(a) defect
(b) clinical findings
(c) clinical associations
(d) prenatal screening results.

Back 35

(a) trisomy 21 (usually meiotic nondisjunction of homologous chromosomes assoc w/increased maternal age)
(b) Mental retardation, flat faces, prominent epicanthal folds, simian crease, gap b/w first 2 toes, duodenal atresia, congenital heart disease (usually ASD).
(c) incrase risk of ALL and Alzheimer's
(d) Quad screen: decr alpha fetoprotein & estriol, increased beta HCG and inhibin A. US shows nuchal translucencey.

Front 36

Edward's Syndrome
(a) defect
(b) clinical findings

Back 36

(a) trisomy 18 (most common trisomy resulting in live birth after Down's)
(b) Severe mental retardation, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease. Death usually within 1yr.

Front 37

Patau's Syndrome
(a) defect
(b) Clinical findings

Back 37

(a) Trisomy 13
(b) severe mental retardation, rocker bottom feet, micropathalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactily, congenital heart disease. Death usually within a yr.

Front 38

Cri-du-chat syndrome
(a) defect
(b) clinical findings

Back 38

(a) microdeletion of short arm of c5 (46xx, or xy, 5p-)
(b) Microcephaly, moderate to severe mental retardation, high pitched crying/mewing, epicanthal folds, cardiac abnormalities.

Front 39

William's syndrome
(a) defect
(b) clinical findings

Back 39

(a) microdeletion of long arm of c7 (deleted region includes elastin gene)
(b) Distinctive elfin faces, mental retardation, well developed verbal skills, cheerful disposition, extreme friendliness w/strangers, cardiovascular problems.

Front 40

22q11 deletion syndromes CATCH-22
(a) Defect
(b) presentation
(c) Syndromes (2)

Back 40

(a) Due to aberrant dev of 3rd and 4th branchial pouches.
(b) Variable presentation including Cleft palate, Abnormal faces, Thymic aplasia, Cardiac defects, Hypocalcemia secondary to parathyroid aplasia.
(A) DiGeorge's: thymic, parathyroid, and cardiac.
(B) Velocardiofacial syndrome-palate, facial, and cardiac

Front 41

Lesch Nyhan Syndrome
(a) inheritence
(b) defect
(c) clinical presentation

Back 41

(a) XL
(b) defect in HGPRT
(c) mental retardation (mild), spastic cerebral palsy, self mutilation, hyperuricemia