Congential Anomalies/Chromosomal Disorders Flashcards
Sem.2
Major congenital anomalies are found in ___ of every ___ births.
3 of every 100 births
What is the percentage of births are complicated by minor birth defects?
10-15%
Who is involved in the multidisciplinary team involved with fetuses with congenital anomalies?
perinatologist (MFM), neonatologist, sonologist, perinatal sonographer, pediatric surgeon, other pediatric specialists, geneticst, obstetrician, perinatal and pediatric social workers, other support personnel
What is chorionic villus sampling?
ultrasound directed biopsy of placenta or chorionic villi (chorion frondosum)
collect fetal cells
What is the chorion frondosum?
active trophoblastic tissue that becomes the placenta
What can CVS detect?
other than chromosomal abnormalities - help diagnose biochemical or metabolic disorders, thalassemia, and sickle cell disease
(hemoglobinopathies)
List the advantages of CVS.
performed early in pregnancy (earlier than amniocentesis), results available within 1 week, and earlier results allow more options for parents
When is CVS performed? (gestational weeks)
10-14 weeks
Why is ultrasound performed before the procedure of CVS?
to determine the relationship between the lie of uterus and cervix and path of catheter (bladder fullness influences relationship), assess fetus in terms of life, normal morphology, and age, and to identify any uterine masses or potential problems that may interfere with the passage of the catheter
What is an amniocentesis?
a test offered to patients at risk for chromosomal abnormality or biochemical disorder that may be prenatally detectable
How quickly are the results available for an amniocentesis?
results available in 1-3 weeks
if rapid results are desired, fluorescence in situ hybridization (FISH) provides limited analysis within 24 hours
What does FISH commonly assess for?
evaluates for numeric abnormalities of chromosomes 21, 13, 18, X, and Y
What is the most common reason why an amniocentesis is performed?
advanced maternal age
What is the risk of having a fetus with Down Syndrome in women 35 or older? 21 years old?
1 in 365
1 in 2000
What is the risk of having a fetus with a general chromosomal anomaly in women 35 or older? 21 years old?
1 in 180
1 in 500
What are other reasons why an amniocentesis is ordered?
history of balance rearrangement in parent or previous child with chromosomal abnormality; history of unexplained abnormal AFP level or abnormal triple screen; fetus with congential anomaly
When is an amniocentesis generally performed?
between 15 and 20 weeks
(may be done as early as 12 weeks, but may lead to development of fetal scoliosis or clubfoot secondary to reduced amount of AF)
For an amniocentesis, where is the optimal collection site for AF?
away from fetus, away from central portion of placenta, away from umbilical cord, and near maternal midline to avoid maternal uterine vessels
With a multifetal genetic amniocentesis, what should be done sonographically before amniocentesis is performed?
include survey of fetal anatomy and growth profiles; determine monozygotic or dizygotic; and determine if multiple sacs and amount of fluid within each sac
After sampling one sac, how can the physician know which sac to do next?
indigo carmine dye can be injected into first sac to show that both sac sampled - presence of clear amniotic fluid indicates second sac has been penetrated when second pass made - if dye stained fluid is visible, indicates first cas penetrated second time
In Rh- patients, what should be avoided in an amniocentesis procedure? What is given to these patients?
the placenta
RhoGAM is administered to all Rh- patients within 72 hours of procedure
What is a cordocentesis? What is sampled?
another method to analyze chromosomes
fetal blood is obtained through needle aspiration of umbilical cord
When will cordocentesis results be availble?
within 2-3 days
What is cordocentesis more commonly used for?
guidance for transfusions to treat fetal isoimmunization
What is AFP and what produces AFP?
alpha-fetoprotein - major protein in fetal serum
produce by yolk sac in early pregnancy and later by fetal liver
Also found in fetal spine, GI tract, liver, and kidneys
How does AFP get into the amniotic fluid?
by fetal urination and reaches maternal circulation or blood through fetal membranes
Why may AFP levels be elevated?
neural tube defects (such as anencephaly and open spina bifida) are most common
abdominal wall defects (omphalocele and gastroschisis), bladder or cloacal exstrophy, ectopia codris, limb-body wall complex, amniotic band syndrome, twin pregnancy, kidney lesion, congential nephrosis, polycystic kidneys and urinary tracy obstruction, placental lesions
How can AFP be measured?
in maternal serum (MSAFP) or from amniotic fluid (AFAFP)
When do MSAFP levels peak?
levels increase with advancing gestational age and peak from 15-18 weeks of gestation
Which AFP measurement increases with fetal age? Which one decreases?
MSAFP levels increase with advancing gestational age
AFAFP decreases with fetal age
How does an omphalocele cause an increase in AFP?
AFP leaks through membrane encasing herniated bowel or liver
How does gastroschisis elevate AFP levels?
AFP diffuses directly into serum and amniotic fluid from herniated bowel, which lacks covering membrane
Is the AFP level higher with a fetus with gastroschisis or omphalocele?
AFP levels are higher in fetus with gastroschisis than in fetus with omphalocele
What is cloacal extrophy?
bladder outside the abdominal wall
What is ectopia cordis?
fetal heart outside the thoracic cavity
What do obstructions of the GI tract cause?
may cause reduced clearance of AFP
AFP may increase in heart failure when what is present?
hydrops, ascites, or lymphangiectasia
Rare causes of AFP elevation include:
hepatitis, maternal herpes virus and resultant fetal liver necrosis, skin lesions, hepatocellular carcinoma, fetal liver tumors
What is a frequent cause of high MSAFP levels?
fetal death
What is the pattern of AFP levels when oligohydramnios is present?
concentrated AFP, so level may be higher
When AFP is elevated and spine and cranium appear normal, what happens to the risk of spinal defect?
risk of fetus actually having small spinal defect is approximately halved
What is the risk of miscarriage from amniocentesis?
1 in 200
What serum markers are tested in a quadruple screen?
AFP, hCG, unconjugated estriol
and newly added dimeric inhibin A
What does the addition of dimeric inhibin A provide to the quad screen?
impoves sensitivity in detecting Down fetuses
Which is better for detecting trisomy 21, quad screen or MSAFP?
quad screen
What would be the result of the quad screen in trisomy 21?
high hCG levels and decreased AFP and estriol levels
What would be the result of the quad screen if trisomy 18 is to be suspected?
decrease in hCG, AFP, and estriol levels
What is a 1st trimester serum marker derived from trophoblastic tissue that is diffused into maternal circulation?
PAPPA
pregnancy associated plasma protein A
What is the pattern of PAPPA throughout pregnancy?
levels increase in maternal serum throughout pregnancy
levels found to be decreased in pregnancies affected by aneuploidy
What does free beta human chorionic gonadotropin screen for in the first trimester?
can be assessed in maternal serum in first trimester to evaluate for increased risk of Down syndrome
What three screening tools can be used to assess for Down syndrome?
PAPP-A, free beta hCG, and nuchal translucency
all are screened in 1st trimester
Which is better for detecting Down syndrome, quad screen or the combination of PAPPA, free beta hCG, and NT?
the combination of PAPPA, free beta hCG, an NT detection rates for Down syndrome are reported to be greater than or equal to that of a quad screen
What is the normal karyotype?
46 chromosomes
22 pairs of autosomes and one pair of sex chromosomes
Define aneuploidy.
abnormality of number of chromosomes
What is the most common aneuploid condition? What is the abnormality?
Down syndrome
has extra chromosome number 21
What causes trisomy?
nondisfunction
failure of normal chromosomal division at time of meiosis
cause is unknown - strong association with advanced maternal age
What is a dominent disorder caused by?
caused by single defective gene (autosomal dominant)
usually inherited by one parent
When inherited, what chance does a dominant disorder have of being passed down during pregnancy?
carries 50% chance that each time pregnancy occurs, fetus will have condition
What is a recessive disorder caused by?
autosomal recessive
caused by pair of defective genes, one from each parent
What is the difference between dominent and recessive disorders?
dominant is caused by a single defective gene, while recessive is caused by a pair of defective genes
When inherited, what chance does a recessive disorder have of being passed down during pregnancy?
parents have 25% chance of having fetus with disorder
What is an example of an autosomal recessive condition?
infantile polycystic kidney disease
Who are carriers of X-linked disorders?
all affected daughters will be carriers for disorders
boys inherit the disorder
What is the chance that males will inherit disorder from their mother being a carrier?
50% chance
daughters each have 50% chance of being carrier
What is an example of an x-linked disorder?
hemophilia (absent clotting protein)
also aqueductal stenosis
What is a multifactoral condition? What is an example?
an abnormal event thar arises because of interaction of one or more genes and environmental factors
anencephaly is an example
What is mosaicism?
a rare occurrence of gene mutation or chromosomal abnormality in portion of individuals cells
How often are chromosomal abnormalities found?
in 1 of every 180 live births
high prevalence of chromosomal abnormalities in patients referred for second trimester amniocentesis
What is a strong indicator of aneuploidy?
This is found late in 1st trimester, when exactly?
abnormal fluid collection behind getal neck
identified between 10 and 14 weeks gestation
What is the pattern of nuchal translucency?
increased with gestational age
Increased NT is associated with an increased incidence of structural defects such as:
cardiac, diaphragmatic, renal, and abdominal wall anomalies
Increased NT also has an increased incidence of…
spontaneous miscarriage and perinatal death
What is the most common aneuploidy?
Trisomy 21
What is the sonographic appearance of Trisomy 21?
nuchal thickness, hygroma, heart defects, duodenal atresia, shortened femurs, mild pyelectasis, mild ventriculomegaly, echogenic bowel, echogenic foci in heart
What are the most common sonographic findings for Trisomy 21?
nuchal thickening, mild ventricular dilation, brachyencephaly, hypoplastic nose, clinodactyly (curved little finger), hyperechoic bowel, sandal gap, shortened limbs, widened pelvis, pyelectasia, echogenic intracardiac focus
What are the cardiac defects of Down syndrome?
atrioventricular septal defect
(formerly called endocardial cushion defect)
ventricular septal defect, persistent ductus arteriosus (if does not close, results in an increased flow of blood to the lungs = persistent), and tetralogy of fallot
What four things are included with tetralogy of fallot?
boot shaped heart
ventricular spetal defect, pulmonary stenosis, right ventricle hypertrophy (because of the backup of blood), and an overriding aorta (displacement of Ao over the ventricular septal defect)
Is there a cure for Down syndrome?
no - just an ease of symptoms
What is the life expectancy for trisomy 21?
40-50 years
What is another name for trisomy 18?
Edward’s syndrome
What is the most common trisomy? Second most common?
trisomy 21
trisomy 18
What is Edward’s syndrome?
extra chromosome 18
associated with abnormal quad screen
What is the statistic for trisomy 18?
occurs in 3 of 10,000 births
Sonographically, what will trisomy 18 look like?
heart defects, choroid plexus cysts, clenched hands, micrognathia, talipes, renal anomalies, cleft lip and palate, omphalocele, CDH, cerebellar hypoplasia
In trisomy 18, clenched fists and over lapping of what fingers may be seen?
index finger overlapping the third and 5th finger overlapping the 4th
What is the prognosis for Edward’s syndrome?
fetus will often spontaneously abort or die very shortly after birth
infants are profoundly retarded
90% of infants die within first year of life
What is trisomy 13?
extra chromosome 13
What is the statistic for trisomy 13?
occurs in 1 in 5,000-20,000 births
Sonographically, what is seen in Patau’s syndrome?
holoprosencephaly, heart defects, cleft lip and palate, omphalocele, polydactyly, talipes, echogenic chordae tendineae, renal anomalies, menigomyelocele, micrognathia
What is the prognosis for trisomy 13?
80% o infants die within first months
surviors profoundly retarted, with multiple deficits and problems
What is triploidy?
result of complete extra set of chromosomes
occurs in 1% of conceptions
What causes triploidy?
often occurs as result of ova being fertilized by two sperm
What is the prognosis of triploidy?
most fetuses will spontaneously abort in first trimester
only 1 in 5000 will continue to 16-20 weeks gestation
mosaic form may be compatible with survival (mental retardation will result)
What is seen sonographically with triploidy?
hydatidiform placental degeneration, heart defects, renal anomalies, omphalocele, cranial defects, facial defects
What is Turner’s syndrome?
absence of X or Y chromosome
What could be a clinical indicator of Turner’s syndrome?
patients may present with elevated MSAFP when a cystic hygroma is present
What is the classic appearace of Turner’s syndrome?
cystic hygroma
What else is seen sonographically with Turner’s syndrome?
(cystic hygroma) cardiac anomalies (coarctation of aorta), hydrops, renal anomalies (horseshoe kidney, renal agenesis, hydronephrosis, and hypoplastic kidney), short femurs
What is the statistic for Turner’s syndrome?
occurs in 1 of every 2500 live births
What is the prognosis for Turner’s syndrome?
most fetuses will spontaneously abort
prognosis especially grave when fetus presents with large cystic hygroma and edema or hydrops
In those who survive Tuner’s syndrome with a regression of the isolated hygroma, what is the prognosis?
females: immature sexual development, amenorrhea, short stature, webbed neck, cubitus valgus (abnormal elbow angle), shield chest with widely spaced nipples, poor hearing, hormone replacement necessary for sexual development, normal intelligence
What are the sonographic signs of intrauterine death?
1st tri: cramping, bleeding, passage of tissue/blighted ovum, no heart motion
2nd tri: absence of fetal movement and heart beat, spalding’s sign, exaggurated curvature of spine, gas in fetal abdomen, dolichocephaly, skin edema, echogenic amniotic fluid
Define preterm labor. Describe warning sings of preterm labor.
onset of labor before 37 weeks
premature rupture of membranes, intrauterine infection, bleeding, fetal anomalies, polyhydramnios, multiple pregnancy, growth restriction, maternal illness (diabetes, hypertension), incompetent cervix, uterine abnormalities
Discuss genetic testing procedures: reasons, advantages, techniques, risks.
CVS-
reason: can help diagnose biochemical or metabolic disorders, thalassemia, and sickle cell disease
advantages: performed early in pregnancy, results available within one week, earlier results allow more options for parents
technique: US determines relationship between lie of uterus/cervix/path of catheter, assess fetus in terms of life/normal morphology/age, and identify uterine masses or potential problems that may interfere with catheter
risks: preterm labor, premature rupture of membranes, fetal injury, fetal limb anomalies (prior to 9wks)
Discuss genetic testing procedures: reasons, advantages, techniques, risks.
AMNIOCENTESIS-
reason: offered to patients at risk for chromosomal abnormality or biochemical disorder that can be prenataly detectable
advantages:
technique: for optimal collection, stay away from fetus, away from central portion of placenta, away from umbilical cord, near maternal midline to avoid maternal uterine vessels
risk: rupture of membranes, preterm labor, fetal injury(rare)
Discuss genetic testing procedures: reasons, advantages, techniques, risks.
CORDOCENTESIS-
reason: analyze chromosomes
Discuss the most common aneuploidy.
Trisomy 21: presence of all or part of thrid 21st chromosome
Sonographically: nucal thickness, hygroma, heart defects, duodenal atresia, shortened femurs, mild pyelectasis, mild ventriculomegaly, echogenic bowel
MOST COMMON defects include atrioventricular septal defect, ventricular septal defect, persistent ductus arteriosus, tetralogy of fallot
Discuss Edwards’ Syndrome.
Trisomy 18: extra 18th chromosome
second most common trisomy
Sonographically: heart defects, choriod plexus cysts, clenched hands, micrognathia, talipes, renal anomalies, cleft lip and palate, omphalocele, CDH, cerebellar hypoplasia
90% die within first year of life (more serious than trisomy 21)
Discuss Pataus’ Syndrome.
Trisomy 13: extra 13th chromosome
Sonographically: holoprosencephaly, heart defects, cleft palate, omphalocele, polydactyly, talipes, echogenic chordae tendineae, renal anomalies, meningomyelocele, micrognathia
80% die within first month - survivors profoundly retarded with multiple deficits and problems
Discuss Turners’ Syndrome.
generic abnormality marked by absence of X or Y chromosome
Sonographically: cystic HYGROMA, cardiac anomalies, hydrops, renal anomalies, short femurs
most fetuses will spontaneously abort, if survive, have normal intelligence
