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35 Cards in this Set
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- Back
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dysmorphic features (upslanting palpebral fissures, epicanthal folds, chort neck, single palmer crease, clinodactyly),
Congenital heart disease (1/3) Atlanto-axial instability* duodenal atresia hypotonia* mental retardation* hypothyroidism* hearing loss* vision concerns* premature senility |
Down Syndrome
Trisomy 21 translocations increased w/ maternal age Karyotype |
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growth retardation and microcephaly (small head)
Eye anomalies* (microopthalmia, colobomas) Scalp defects Congenital cardiac malformations* polydactyly holoprosencephaly-type cerebral malformations* severe neurologic dysfunction cleft lip and palate |
Trisomy 13
Increased w/ maternal age Karyotype |
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Typically lethal, most die within first year
failure to thrive/small for gestational age Congenital heart disease* severe mental retardation* dysmorphic features (hand clenching, rocker bottom feet |
Trisomy 18
47+18 most are trisomy, 20% are translocations Increased w/ maternal age Karyotype |
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congenital heart defects*
dysmorphic features (lymphedema, wide spaced nipples, webbed neck) renal malformations* short stature (responds to growth hormone failure to enter puberty* (estrogen treatment) infertility* mild isolated learning disabilities |
Turner Syndrome
45X Monosomy X Karyotype |
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tall and thin
hypogonadism at puberty* (infertility*, small testes) isolated learning disabilities* |
Klinefelter Syndrome
47XXY Karyotype |
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Congenital heart disease*
palate abnormalities (cleft palate, velopalatal insufficiency* thymic hypoplasia (immunodeficiency* hypoparathyroidism with hypocalcemia* Dysmorphic features (cleft palate, broad nose, triphalangeal thumbs, wide spaced eyes (hypotelorism), abnormally shaped ears) Increased freq. behavioral/psychiatric disorders* |
DiGeorge Syndrome .
22q11.2 Syndrome velocardiofacial syndromechromosome microdeletion (contiguous gene) syndrome 93% are de novo CMA, FISH to confirm |
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Congenital heart disease* (supravalvular aortic stenosis
mild developmental delay (language)* loquacious personality Dysmorphic facial features (broad mouth, prominent ears, small pointed chin) hypotonia hypersensitivity/anxiety short stature calcium abnormalities |
Williams Syndrome
Chromosome microdeletion (7q11.2) most are de novo CMA, FISH to confirm |
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skeletal (tall stature, pectus, scoliosis*, loose joints*, dolicostenomelia (long limbs), hernias*, pneumothorax*
eyes (myopia (near sighted), lens dislocation*) cardiac (mitral valve prolaps, aortic root dilatation risk for dissection*) |
Marfan syndrome
autosomal dominant variable expressivity Fibrillin gene ASO |
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Rhizomelic short stature
megalencephaly (large head with frontal bossing) spinal cord compression* normal IQ |
Achondroplasia
autosomal dominant fully penetrant most are de novo gain of function mutations FGFR3 mutations Homozygous lethal ASO |
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café au lait spots
axillary and inguinal freckling cutaneous neurofibromas* lisch nodules (iris hamartomas plexiform neurofibromas optic gliomas bony lesions mild learning disabilities |
Neurofibromatosis
Autosomal dominant variable expressivity tumor suppressor gene loss of function mutations Allelic heterogeneity ASO |
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carpet-like presentation of polyps (>100)*
extremely high risk for colon cancer by age 40 prophylactic colectomy recommended upper GI polyps also common* |
Familial Adenomatous Polyposis (FAP)
Autosomal dominant, Tumor suppressor gene ASO |
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Increased risk for breast and ovarian cancer*
increased screening or prophylactic mastectomy and oophorectomy male breast cancer with BRCA2 mutations |
BRACA
Autosomal dominant, two identified genes: locus heterogeneity variable penetrance tumor suppressor gene specific mutations common with individuals of ashkenazi Jewish ancestry ASO |
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high cancer risk
soft tissue sarcoma/osteosarcomal Leukemia melanoma cancer of colon, breast, pancreas, adrenal cortex, brain poor screening/surveillance |
Li Fraumani
Autosomal dominant p53 gene tumor suppressor gene ASO |
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tumors may be bilateral or unilateral
bilateral cases are due to germline mutations unilateral cases may be germline or somatic tumors typically present before age 5 yrs increased risk for non-ocular cancers later in life |
Retinoblastoma
germline or somatic mutation germline - autosomal dominant tumor suppressor gene Knudsons two-hit hypothesis 90% Penetrant ASO |
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adult onset neurodegenerative disease
motor disturbances cognitive deterioration behavioral disturbances no treatment |
Huntington Cholera
triplet repeat expansion of HD Gene autosomal dominant CAG, polyglutamine expansion anticipation presymptomatic testing not performed on minors PCR Amplification and gel electrophoresis separation/southern blotting |
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onset in infancy to adulthood
pulmonary disease* Pancreatic insufficiency* elevated sweat chloride infertility (obstructive azoospermia) growth failure |
Cystic Fibrosis
Autosomal Recessive ethnic variation in freq variable expressivity monogenic, multi allelic (CFTR gene) ASO |
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Typically infantile onset
neurodegeneration cherry red spot in retina psychosis death typically by age 3 |
Tay Sachs
lysosomal storage disorder (hexosaminidase A deficiency Autosomal Recessive ethnic variation in allele freq most common Ashkenazi Jew ASO |
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newborn screening
asymptomatic until brain damage has occurred (short stature, mental retardation, behavioral problems) treated with major diet restriction of Phe maternal --- - high maternal --- levels affect normal fetus, resulting in an infant with severe mental retardation |
Phenylketonuria
Autosomal Recessive Most common enzyme deficiency Phenylalanine hydroxylase PAH deficiency ASO |
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newborn screening
failure to thrive liver failure developmental delay cataracts dietary restriction of lactose improves outcome w/o treatment - life-threatening |
Galactosemia
newborn screening failure to thrive liver failure developmental delay cataracts dietary restriction of lactose improves outcome w/o treatment - life-threatening ASO |
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anemia
pain crises asplenia |
Sickle Cell Anemia
Autosomal Recessive Monogenic, monoallelic Beta hemoglobin heterozygote advantage in malarial zones ethnic variation in allele freq common w/ African descent |
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anemia, thrombocytopenia
hepatosplenomegaly bone involvement poor growth enzyme replacement therapy |
Gaucher Disease
Autosomal Recessive most common lysosomal storage disorder (glucocoerebrosidase deficiency ethnic variation inf allele freq - most common Ashkenazi variable severity ASO |
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variable presentation depending on disorder and disease severity. Presentation caused by accumulation of material in lysosomes - variable organ presentation, enzyme replacement available for several disorders
mucopolysaccharide diseases may involve: CNS, Heart, Skeletal system, Pulmonary system, Liver, Auditory/vision (not Hunter) |
Storage Disorders
Most Autosomal Recessive (except Fabry (X-linked), mucopolysaccharidosis Type II (Hunter Syndrome) (X-linked)) varying enzyme deficiencies |
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progressive muscle weakness - childhood onset
calf hypertrophy elevated serum creatine kinase level mild intellectual compromise |
Duschenne Muscular Dystrophy
X-linked monogenic, multi allelic (dystrophin gene) new mutations relatively freq carriers have some clinical features multiplex PCR, gel / ASO |
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seizures*
mental retardation* little to no speech* happy puppet syndrome (inappropriate smiling/laughing, ataxia microcephaly (small head) |
Angelmann Syndrome
imprinting defect absence of maternally derived 15q11-q13 (microdeletion (70%), uniparental disomy (7%), mutations in UBE3A (10%), imprinting defect (3%) Abnormal methylation studies southern blotting, CMA, FISH, |
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morbid obesity
food seeking behavior hypogonadism mental retardation* at risk for obesity-related diseases (sleep apnea, cor pulmonale (heart failure due to pulmonary hypertension), diabetes mellitus |
Prader Willi
imprinting defect Absence of paternally derived 15q11-q13 (microdeletion (70%), uniparental disomy (30%), imprinting center defect (rare) southern blotting, CMA, FISH, |
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Autosomal Dominant
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Marfan Syndrome
Achondroplasia Neurofibromatosis Familial Adenomatous BRACA Li fraumeni Retinoblastoma Huntington Cholera |
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Autosomal Recessive
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Cystic Fibrosis
Tay Sachs Phenylketonuria Galactosemia Sickle Cell Disease Gaucher Disease |
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mental retardation*
ADHA/autistic spectrum behaviors dysmorphic features (large head, long face, large ears, macroorchidism, prominent jaw and forehead) |
Fragile X Syndrome
Triplet repeat expansion disease (CGG repeat in the FMR1 gene) X-linked somatic mosaicism Expansion (maternal inheritance) PCR Amplification and electrophoresis separation |
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PCR Amplification and electrophoresis separation
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Huntington Cholera
Fragile X Syndrome |
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Karyotyping
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Down Syndrome (Trisomy 21)
Trisomy 13 Trisomy 18 Turner Syndrome (45X - monosomy X) Klinefelter syndrome (47XXY) |
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southern blotting, CMA, FISH
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Angelmann Syndrome
Prader Willi |
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ASO
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Marfan's Syndrome (Fibrillin gene)
Achondroplasia (FGFR3 mutation) Neurofibromatosis (tumor sup.) Familial Adenomatous Polyposis BRACA Li Frameni Retinoblastoma Cystic Fibrosis (CFTR) Tay Sachs (hexoaminosidase def) PKU Galactosemia (enzyme test) Sickle Cell Gaucher Disease (glucocerebrosidase) |
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CMA, FISH to confirm
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DiGeorge Syndrome (22q11.2 microdeletion)
Williams Syndrome (7q11.2 microdeletion( |
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PKU Testing
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Mass spectrometry
Guthrie test |
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multiplex PCR, gel/ASO
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Duchenne Muscular Dystrophy
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