Prenatal screening, dx, tx Flashcards
cystic fibrosis - what kind of inheritance?
AR
median survival for CF patients
30 years
what are the 2 most common mutations in CF?
deltaF508 and G542X
what is risk of fetus being + for an AR disorder if both mother and father are carriers? What is next step if both parents are found to be carriers?
25%. Amniocentesis or CVS to dx fetus.
rate of CF carriers among caucasians
1 in 28
pattern of inheritance for sickle cell
AR
who should be screened for sickle cell?
all pg AfAms
pattern of inheritance for tay-sachs
AR
signs & sx’s of tay-sachs:
occur 3-10mos after birth. loss of alertness hyperacusis progressive neuro'c degeneration, dvp'l delay myoclonic & akinetic seizures cherry-red spots on retina (macular fovea centralis is red, macula is pale) paralysis, blindness, dementia death by age 4
Tay-Sachs is a def’y of what?
enz def’y (hexA) which is responsible for ganglioside degradation.
Results in ganglioside accumulation in brain gray matter neurons => neuronal death.
who gets screened for Tay-Sachs
ashkenazi Jews, French canadians
when is beta thalassemia dx’d? More common in who?
several months after birth, when the beta-globin chain starts to replace fetal gamma-globin chains. More common in Mediterranean, Asian, African
what are the different types of alpha thalassemia?
4 diff alleles encode alpha globin gene.
Deletion of 1 alpha-globin gene = silent carrier, asx’c.
deletion of 2 = alpha-thal trait. Normal Hb electrophoresis, mild pht.
deletion of 3 = HbH dis. excess beta chains
accumulate
deletion of all 4 = hydrops fetalis. They only produce HbBart.
how do you screen for thalassemias?
do a CBC in high-risk populations. If microcytic anemia is found, then do Hgb electrophoresis.
cis vs. trans mutations of alpha globin gene: which is more common in who?
cis = 2 alpha globin muts, both on same chrom. More common in Asians. trans = 2 alpha globin muts, on diff chroms. More common in Africans.
why is dtm’n of cis vs. trans mutation important?
if both parents have cis mut, then there’s a 25% chance that fetus will dvp hydrops fetalis. If both have trans, the child will get the trans mut and will be an asx’c carrier.
when to screen for trisomy 21 and how?
use triple or quad screen, b/w 15 and 19 weeks (second trimester)
first trimester screen for down syndrome =
nuchal translucency + b-hCG + PAPP-A (pg’y-ass’d plasma prot A)
Trisomy 18 is screened for how?
triple screen during 2nd tri
findings of trisomy 18 (Edward syndrome)
clenched fists, overlapping digits, rocker bottom feet seen on u/s. VSD, tetralogy of fallot, omphalocele, congenital diaphragmatic hernia, neural tube defects, choroid plexus cysts.
Incompatible w/life beyond age 2.
Trisomy 13 is screened for how?
Not detected by triple screen but on routine screening u/s. CP is similar to trisomy 18. Most do not live beyond 1 year. Holoprosencephaly, cleft lip, cleft palate, cystic hygroma, single nostril or absent nose, omphalocele, hypoplastic left heart, club foot, club hand, polydactyly, overlapping fingers.
what are the most common sex chromosome abnormalities?
Turner (45X), Klinefelter (47XXY)
CP of turner syndrome
pht’lly female, primary amenorrhea, webbed neck, low-set ears, wide carrying angle, shield chest, short 4th metacarpal, renal anomalies, lymphedema, coarctation of aorta, cystic hygroma seen on prenatal u/s.
screening for Turner syndrome?
none. Dx’d w/CVS.
screening for Klinefelter syndrome?
none. Dx’d w/CVS.
CP of Klinefelter:
small, firm testes at puberty, infertility, gynecomastia, mental retardation, elevated gonadotropin levels.
what 2 chromosomal abnormalities are screened for on the triple or quad screens?
Trisomy 21 and 18.
what is a morula & when does it dvp?
16-cell embryo, day 4
what is blastocyst?
product of morula separating into inner & outer cell mass. Implants into endometrium by week 1
what does trophoblast become?
placenta
inner cell mass becomes the…
bilaminar disk, composed of epiblast & hypoblast
what is gastrulation & when?
form’n of primitive streak on epiblast, then formation of 3 germ layers. Occurs during week 3.
what does each germ layer give rise to?
endoderm => GI and resp’y systems
mesoderm => CV, msk, GU systems
ectoderm => skin, nervous system, sensory organs
when does organogenesis occur
week 3 to 8 after conception (5-10 of GA)
when does neural tube form?
day 22-23
when do most neural tube defects occur and why
occur by week 4, as a result of failed closure of neural tube
spina bifida findings on u/s
“lemon” sign - concave frontal bones
“banana” sign - cerebellum pulled caudally & flattened
ventriculomegaly
club feet
what MSAFP finding occurs in neural tube defects?
elevated MSAFP levels
when does cardiac development occur?
week 3
what is the bulbus cordis
caudal section of the heart tube. Develops into trabeculated part of RV, outflow tracts of both ventricles, and proximal aorta & PA
how does cardiac septum form
endocardial cushions separate atria from ventricles. Atria divide into R and L by septum primum and septum secundum
what is Eisenmenger syndrome:
VSD or PDA initially causes L–>R shunt. W/time, RVH dvps, => pulm HTN, dir of flow thru shunt reverses (now R–>L)
what are the cardiac findings of tetralogy of fallot
VSD
overriding aorta
pulm a. stenosis
RVH
what is the ductus arteriosus?
vessel connecting PA to aorta in fetus. Shunts de-O2’d blood from PA away from undvp’d fetal lungs into systemic circl’n.
what is potter syndrome?
bilat renal agenesis or distal urinary obstr’n => anhydramnios => pulm hypoplasia, contractures
how do kidneys dvp?
3 “scafffolds” dvp and regress sequentially.
1) Pronephros - nonfct’l
2) Mesonephros - temporarily fct’l, => formation of mesonephric duct (Wolffian).
Ureteric bud comes off of it - forms collecting tubules, calyces, renal pelvis, ureter.
3) Metanephros - forms nephrons. Gets connected to ureteric bud.
what does Wolffian (mesonephric) duct become?
in males, epididymis, vas deferens, ejaculatory duct, seminal vesicles.
In females, degenerates. Gartner duct remains (can have cyst formation)
what happens if ureteric bud does not contact the metanephros?
nephrons do not connect to collecting tubules => renal agenesis. Potter syndrome ensues.
what does the bladder derive from?
UG sinus
what is the urachus?
The obliterated allantois. A fibrotic cord that becomes median umbilical lig.
what is the allantois?
embryonic structure responsible for waste collection and oxygenation.
tx for Potter syndrome
none. Have attempted in utero ablation of urinary obstruction if that was the cause, but conflicting results.
what is a first-tri screen for aneuploidy?
Nuchal translucency
what is a second-tri screen for aneuploidy?
MSAFP, triple screen, quad screen
triple screen findings for Trisomy 21
low MSAFP
low estriol
high b-hCG
triple screen findings for Trisomy 18
low MSAFP
Low estriol
Low b-hCG
what does a +LR tell you?
ex: a 37 yo G1P0 has an odds of 2.0 (made that up) of giving birth to a Downs baby. The MSAFP test has a +LR of 1.5.
You need pre-test odds. Then if pt tests +, the odds is increased by a that amt.
ex: if she tests + on the MSAFP (has a low level), her odds increases from 2.0 to 3.0 of having a downs baby.
what is an echogenic intracardiac focus?
a “soft call” u/s finding c/w Down syndrome
is a calcification of papillary m. w/no obvious pathophysiology
what are the 3 methods of prenatal dx?
amniocentesis
CVS
percutaneous umbilical blood sampling
how is amniocentesis done & when?
done anytime after 15 weeks. Needle placed through mom’s skin into uterus to sample some of amniotic fluid, collect sloughed fetal cells, cells are cx’d and karyotyped or FISHed.
who gets amniocentesis?
parents who are known carriers of genetic dis.
offered to all moms of AMA
what is the risk of miscarriage for amniocentesis?
1 in 200
how is CVS done and when?
done b/w 9 and 12 weeks. Needle placed transabdominally or transvaginally. Chorionic vili from placenta are sampled. Results are quicker than amniocentesis.
what is risk of miscarriage for CVS?
higher than 1 in 200
how can false +’s occur in CVS?
rare cases of confined placental mosaicism. Cells of placenta that are sampled during CVS do not reflect fetal cells.
when is PUBS done?
when fetal hct m/b obtained - w/u of fetal anemia, Rh isoimmunization
rapid karyotype analysis (no need to cx cells like in amnio or CVS)
diff b/w level I and level II u/s?
level I u/s is a screening u/s, done b/w 18 & 22 weeks.
level II u/s can better pick up congenital anomalies, is ordered when level I is abnormal.
when is fetal echocardiography used?
in pts at high-risk for cardiac anomalies, esp pregestational DM
when is fetal MRI used?
to eval for hypoxic brain injury
what is a 3D u/s?
makes an image that looks more like a fetus, but doesn’t offer any more dx’c ability than a 2D u/s.
