Ch 3 Prenatal Screening , DX, treatment

Question 1

screening allows hhigh rriskk individuas to be selected out of low risk population at risk for a givenn diagnosis or complication

Answer 1

t

Question 2

cell-free fetal dna (cffdna) is a test recently developed that may maximize sensitivity and minimize false positives, but not currently a diagnostic test

Answer 2

t

Question 3

cystic fibrosis is an autosomal recessive disease . all CF patients have chronic lung disease because of recurrent infections, leading eventually to irreversible lung damage and strain on the right ventricle (cor pulmonale)
85% - pancreatic insufficiency manifested by chronic malabsorption and failure to thrive.
median survival rate is close to 40 years for CF patients born today

Answer 3

t

Question 4

C.F. mutations common in caucasians. 1:25 is..

Answer 4

A carrier

Risk of carrier status less common in other races / ethnicities such as Asian and Hispanic.

Question 5

Sickle cell anemia - autosomal recessive causes by single point mutation in the gene for beta chain in hemoglobin. The resulting hemoglobin (hb s) forms polymers that when deoxygenated cause the cells to lose their biconcave shape and become sickles in appearance. As a result patients have hemolytic anemia, shortened life expectancy, and frequent pain crisis secondary to vasooclussion of small vessels by dystrophin erythrocytes.

Answer 5

T

Question 6

Ray Sachs AR that is most common in Jewish and French Canadians

Answer 6

T

Question 7

Ray Sachs infants develop symptoms 3-10
Months after birth - loss if alertness, and excessive reaction to noise. There is progressive developmental delay and neurological function. Typically suffer from paralysis, blindness, dementia, and die by age 4

Answer 7

T

Question 8

thalassemias are set of hereditary hemolytic anemias that are caused by mutations that result in reduction in synthesis of either alpha or beta chains that make up hemoglobin molecule. reduction in a particular chain leads to imbalance of globin chain synthesis and subsequently a distortion in alpha: beta ratio. as a result, unpaired globin chains produce insoluble tetramers that precipitate in the cell and cause damage to membranes.

Answer 8

t

Question 9

b-thalassemia, there is impairment of beta chain production that leads to excess of alpha chains.

Answer 9

t

Question 10

heterozybous beta thalassemia will have a mild hemolytic anemia and low MCV < 80they can be screened by getting a complete blood count (CBC)

confirmation will be made by hemoglobin electrophoresis, which will show an increase in alpha:beta ragio (hgb A2)

Answer 10

confirmation will be made by hemoglobin electrophoresis, which will show an increase in alpha:beta ragio (hgb A2)

Question 11

alpha thalassemia is encoded by 4 alleles on 2 chromosomes. additionally, 2 of the 4 mutations can occur cis or trans, with cis being on same chromosome, and trans being on different chromosomes.
cis mutations are seen more commonly among asians.
trans mutations more commonly among africans

Answer 11

t

Question 12

most severe form of alpha thalassemia causes fetal hydrops and is incompatible with life. infants are delivered preterm and are pale, hydrophic, severely anemic, and have spleomegaly.
a fetal hemoglobin electrophoresis would reveal no hbf, no hba, and approximately 90-100% hbalpha4 also referred to as Hb Bart.

Answer 12

HbBart - no hbA all 4 missing

Question 13

Hemoblobin H - deletion of 3 alpha globin genes, resulting in accumulation of excess beta chains in red cell.

Answer 13

hemoglobin h - membrane damage results, and these rbcs are susceptible to early clearance and destruction. infants develop moderate hemolytic anemia, and the initial hemoglobin electrophoresis shows some HbBart and some HbH.

Question 14

1st trimester screening includes:

Answer 14

NT, combined with PAPP-A and b-hcg

Question 15

2nd trimester portion is called quadruple (quad) screen and includes

Answer 15

maternal serum alpha fetoprotein (msafp), estriol, b-hcg, and inhibin

Question 16

ccfdna in maternal serum to make a noninvasive prenatal diagnosis.
limitations of this test”:

Answer 16

twins,

chromosomal mosaicism

Question 17

trisomy 21 - extra chromosome 21 most common cause of down syndrome. phenotype of down syndrome is

Answer 17

short stature
classic facies
developmental delay
mental retardation with IQ from 40-90
associated anomalies include: cardiac defects, duodenal atresia or stenosis, and short limbs.
combination of 1st trimester and quad screen - 95%
40-60% cannot be diagnosed via ultrasound

Question 18

trisomy 18 ( Edward syndrome) assciated with multiple anomaies which are seen on ultrasound. in 95% of cases

Answer 18

t

Question 19

patients whose MSAFP is elevated without an elevated amniotic fluid or other etiologies have been found to be at greater risk of pregnancy complications associated with the placenta:

Answer 19

placental abruption, preeclampsia, intrauterine growth restriction, and possibly intrauterine fetal demise.
these probelms have been associated with elevated b-hcg as well.

Question 20

trisomy 18 soft findings associated with a choriod plexus cyst

Answer 20

t18 associated with chorioid plexus cyst

Question 21

down syndrome has been asscoiated with many ultrasound findings, most notably echogenic intracardiac focus (EIF)

Answer 21

t21 asscoated with echogenic intracardiac focus (EIF)
EIF is acalcification of the papillary muscle without any particular pathophysiology. it si seen in 5% of pregnancies and is more common in fetuses of asian women.

Question 22

serum screens in 1st trimeser and 2nd trimester do not screen for sex chromosome abnormalities. having a normal screen does NOT reduce the risk . Turner syndrome will commonly be found on 1st trimester NT screen because these patients have cystic hygroma. however, this does not reduce risk of sex chromsomeal abnormality below a screening threshold.

Answer 22

t

Question 23

most common sex chromosomal abnormalities:

Answer 23

turner synbdrome
klinefelter syndrome
appear to be due to paternal nondysjunction rather than maternal, thus maternal age itself does not appear to be a risk factor.

serum screens in 1st trimeser and 2nd trimester do not screen for sex chromosome abnormalities.

Question 24

NTD are increased in setting of diabetes and women with seizure disorder. latter is associated with use of several antiepileptic drugs, including carbamazepine and valproic acid.
lithium - epstein anomaly - displacement of tricuspid valve
fluoxetine and other SSRI - assciated with increase in fetal cardiac anomalies.
prednisone - does not cross placenta but can lead to hyperglycemia which may in turn cause fetal effects.

Answer 24

t

Question 25

low calcium intake has been shown to be associated with preeclampsia

Answer 25

t

Question 26

low dose aspirin as been shown to slightly reduce risk of preeclampsia, and both low dose aspirin and low m olecular weight heparin been used in women with htrombophilias.

Answer 26

t

Question 27

NT sono alone has 70% sensitivity, and when added to serum screen, the two together have 80% sensitivity.

sequential screen is a test that combines 1st trimester and second trimester tests. this combination gets to 90-95% sensitivity, so it has a greater sensitivity than 1st trimester screening alone

Answer 27

t

Question 28

ultrasound poor screening test for down syndrome , DS fetus will have findings on ultrasound about 60% of the time.

Answer 28

t

Question 29

classic cardiac anomaly in down syndrome is

Answer 29

av canal defect.

pyloric stenosis is common and should raise concern for down syndrome

Question 30

quad screen with low estriol, bhcg and msafp is consistent with trisomy 18. findings of the multiple anomalies on ultrasound, inccludnig growht restriction.

Answer 30

ultrasound of t18

increased amniotic fluid, clubfoot, omphalocele, choroid plexus cyst, and possible heart defect.

Question 31

trisomy 13 also have multiple anomalies on ultrasound

Answer 31

t

Question 32

t21, turner syndrome, and kleinfelter syndrome will all have a normal ultrasound.

Answer 32

all have normal ultrasound for

t21, turner, kleinfelter (sex chromosome mutation)

Question 33

array cgh can be performed on cells from amniocentesis to look for microdeletions.

Answer 33

array chg = microarray comparative genomic hybridization

Question 34

noninvasive prenatal diagnostic testing using free fetal dna in maternal circulation is available for trisomies 21, 19, 13.

Answer 34

trisomies 21, 19, 13.