Genetic Disorders (Ch 6) Flashcards
1
Q
Down Syndrome
A
- Trisomy 21: 47XX/XY+21
- MC chromosomal disorder (1 in 700 births)
- risk increases with AMA
- pathogenesis = meiotic nondisjunction (95%) robertsonian translocation (4%) mosaicism due to mitotic nondisjunction during embryogenesis (1%)
- screen prenatally w maternal serum levels of α-fetoprotein (decreased) chorionic gonadotropin (increased) and unconjugated estriol (decreased) and inhibin A (increased)
- Dx with karyotype or FISH
- new test: cell free fetal DNA by PCR (not invasive)
2
Q
Down Syndrome Symptoms
A
- severe mental retardation (MCC genetic MR)
- mongoloid facial features (flat face (absence of cartilage) low-bridged nose, epicanthyl folds)
- brush field spots (white areas of fibrosis in iris –> speckled appearance of iris)
- muscular hypotonia
- broad short neck (increased nuchal lucency)
- palmar (simian crease)
- congenital heart defects
- endocardial cushion defect (if present) leads to AV canal (a common connection btw all 4 heart chambers)
- gap btw 1-2nd toes
- intestinal stenosis
- umbilical hernia
- may develop duodenal atresia (see double bubble sign on Xray (stomach and duodenal air bubbles)
- see polyhydramnios on fetal US
- hirschsprung disease
- predisposed to leukemia: increased risk (15-20x) of ALL (kid less than 3 with Downs –> AML M7; Kid 3-7 w Downs: ALL)
- Alzheimer disease by 40
3
Q
robertsonian translocation
A
- translocation involving 2 acrocentric chromosomes with the break points occurring close to the centromeres
- results in an extremely large chromosome and a tiny one (that’s typically lost)
4
Q
green projectile vomiting
A
- duodenal atresia
- pyloric stenosis: not green; palpable olive
5
Q
myocardium derived from
A
- mesodern
- cardiac cushion derived from ectoderm (neural crest)
6
Q
Edwards Syndrome
A
- Trisomy 18: 47XX/XY +18
- prominent occiput
- mental retardation
- low-set ears
- micrognathia (small jaw)
- short neck
- overlapping fingers
- congenital heart defects
- horseshoe kidney
- limited hip abduction
- rocker bottom feet (loss of arches due to excess CT)
- poor prognosis due to severe congenital malformations
- increases with AMA
- caused by nondisjunction
7
Q
Cri du chat
A
- 46 XX/XY 5p-
- due to deletion of short arm of chromosome 5
- high-pitched catlike cry (due to too much CT in neck –> increases pitch)
- mental retardation
- congenital heart disease (cushion defect –> VSD)
- microcephaly
8
Q
Patau Syndrome
A
- trisomy 13
- microcephaly and mental retardation
- holoprosencephaly
- midline facial defects
- microphthalmia (eyes smaller than normal)
- cleft lip and palate
- cardiac defects
- umbilical hernia
- renal defects
- polydactyly (6 fingers)
- rocker bottom feet (loss of arches due to excess CT)
- increases with AMA
- caused by nondisjunction
9
Q
- severe mental retardation
- mongoloid facial features (flat face (absence of cartilage) low-bridged nose, epicanthyl folds)
- brush field spots (white areas of fibrosis in iris –> speckled appearance of iris)
- muscular hypotonia
- broad short neck (increased nuchal lucency)
- palmar (simian crease)
- congenital heart defects
- endocardial cushion defect (if present) leads to AV canal (a common connection btw all 4 heart chambers)
- gap btw 1-2nd toes
- intestinal stenosis
- umbilical hernia
- may develop duodenal atresia (see double bubble sign on Xray (stomach and duodenal air bubbles)
A
Down Syndrome
10
Q
microdeletion 13q14
A
retinoblastoma gene
11
Q
microdeletion 11p13
A
WAGR complex: wilms tumor, aniridia, genitourinary anomalies, mental retardation
12
Q
klinefelter syndrome
A
- 47XXY (only guy with barr body)
- “kinky klinefelter, too much X”
- caused by meiotic nondisjunction
- common cause of male hypogonadism (streaked with fibrosis)
- elevated FSH and LH, low levels of testosterone
- testicular atrophy, infertility due to azoospermia, eunuchoid body habits (wide hips), high pitched voice, female distribution of hair, gynecomastia (get breast cancer bc unopposed estrogen)
- get seminomas bc streak testes
- weak bones bc low T
13
Q
- prominent occiput
- mental retardation
- low-set ears
- micrognathia (small jaw)
- short neck
- overlapping fingers
- congenital heart defects
- horseshoe kidney
- limited hip abduction
- rocker bottom feet (loss of arches due to excess CT
A
Edwards Syndrome (Trisomy 18)
14
Q
Turner Syndrome
A
- 45 XO
- common cause female hypogonadism
- second X chromosome necessary for oogenesis and normal development of ovary. No Barr body present on histo exam of cells
- fail to develop secondary sex characteristics
- have short stature with widely spaced nipples
- abnormal sexuality: gonadal dysgenesis with atrophic ‘streaked’ ovaries (at risk for dysgerminoma), primary amenorrhea, infertility
- cystic hygroma (dilated and proliferating lymphatics (light shines through it aka “trans illumination of neck”) –> webbed neck
- hypothyroidism
- congenital heart disease (preductal coarctation of aorta and bicuspid aortic valve)
- low posterior hairline
- cubitus valgus (elbows turned in)
- pigmented nevi (brown spots)
- small fingernails
- peripheral lymphedema (swollen feet)
- hydrops fetalis
- females with 45 X, 46 XY mosaicism (most deadly, at risk for hydrous fetalis) are at risk for gonadoblastoma of ovary
- low Estrogen, high LH/FSH (aka born with menopause)
- low E –> short and osteoporosis
- stature homeobox: short bc haplotype insufficiency
15
Q
4 causes of hydrops fetalis
A
- dead, swollen babies
- turners
- α-thallisemia (4 deletions)
- RH incompatibility
- parvo B19 (infects RBC precursors)
