Prenatal Genetic Questions Flashcards
Chorionic villus sampling (CVS) occasionally produces cytogenetic results that are somewhat ambiguous such as mosaicism. The finding of a mosaic trisomy 15 in a CVS leads to a secondary amniocentesis, which demonstrated a normal diploid karyotype. In such a case which of the following clinical options would be the best response?
A. Consider uniparental disomy molecular cytogenetic studies for chromosome 15
B. Monitor the pregnancy with targeted ultrasound for cardiac malformations.
C. Perform cordocentesis (funicentesis) to confirm normal karyotype in fetal blood.
D. Reassure the parents that the baby will be normal during a discussion of the results.
E. Suggest consideration of termination of pregnancy for fear of hidden ‘tissue mosaicism”
The correct answer is A. – one etiology of mosaicism is considered to be an initially trisomic conception which undergoes trisomic rescue, this would put the pregnancy at risk for retention of two chromosomes from the same parent, uniparental disomy testing would be indicated. Ultrasound surveillance is indicated for growth restriction but not for congenital anomalies such as cardiac malforamation. Low level tissue mosaicism can never be disproven in the fetus.
Which of the following chromosome studies would most likely be detected in a phenotypically normal woman with infertility?
A. 46,XY
B. 45,X
C. 46,XX/45,X
D. 47,XXY
E. 47,XYY
The correct answer is C. – 46,XX/45,X can present as a phenotypically normal female with infertility, Answer A could be a phenotypically normal female but genetically be a male with complete androgen insensitivity and would have amenorrhea.but is less common. Answer A would present with Turner syndrome phenotype. Answers D and E present as males.
Fragile X testing should be considered during infertility evaluations when you encounter which of the following clinical findings?
A. azoospermia
B. oligospermia
C. partial androgen insensitivity
D. polycystic ovarian syndrome
E. premature ovarian failure
The correct answer is E. – POF is the only impact on reproductive capacity recognized among fragile X carriers
The risk of pregnancy loss is considered to be the highest with which of the following prenatal procedures?
A. amniocentesis - standard (> 15 weeks)
B. amniocentesis - early (< 12 weeks)
C. chorionic villus sampling
D. fetal magnetic resonance imaging study
E. first trimester nuchal lucency determination
The correct answer is B. – at a loss rate of 2-3%, early amniocentesis out paces the risk of losses from CVS (1.0%) and standard amniocentesis (0.5%), MRI and nuchal lucency measurement are noninvasive and not associated with pregnancy loss
The laboratory at your center is seeking your advice regarding introduction of array Comparative Genome Hybridization (aCGH) as an option for prenatal diagnostic testing from chorionic villus sampling and amniocentesis. You can counsel the laboratory administration that, when compared to conventional karyotype analysis, aCGH is associated with which of the following features?
A. Increases detection for submicroscopic deletions
B. Produces more uninterruptible results from stillbirth specimens
C. Requires a greater volume of amniotic fluid
D. Requires greater technician skill
E. Requires longer cell culture time
The correct answer is A. – Implementation of aCGH in the prenatal setting may be advantageous for several reasons including increased detection of genomic disorders when ultrasound malformations are present and the conventional karyotype is normal and when poor cell growth is anticipated (stillbirth or miscarriage). The ability of aCGH to utilize smaller volumes of fluid and the applicability for automation may also prove valuable components. Current trials are underway to address aCGH versus conventional karyotype in routine amniocentesis with the issue of CNV to be addressed.
When noted as an isolated finding on second trimester ultrasound, findings such as choroid plexus cyst, echogenic bowel, echogenic cardiac focus, or short femur are most likely occur in a fetus with which of the following outcomes?
A. cystic fibrosis
B. Down syndrome
C. trisomy 18
D. normal infant
E. tuberous sclerosis
The correct answer is D. – each of these findings in isolation can occur in as many as 1-5% of pregnancies; in the majority of instances the karyotype is normal. As aneuploidy is a relatively rare event, although the relative risk of aneuploidy is indeed increased (1.2 to 5.0 fold), the majority of pregnancies are karyotypically normal. Echogeneic bowel is associated with cystic fibrosis with an increased relative risk but again the majority of infants with echogenic bowel are normal. None of the findings are seen in fetuses with tuberous sclerosis.
Among
encountered by the infertility specialist?
causes of premature ovarian failure, which of the following would be most commonly be encountered by the fertility specialist?
A. 46, XY female
B. 45, X
C. fragile X premutation carrier
D. galactosemia
E. myotonic dystrophy
The correct answer is C. – Amenorrhea would be expected with A (Androgen insensitvity) and B (Turner syndrome) Galactosemia is rare in itself , so an infertility specialist will only rarely encounter a patient. Myotonic dystrophy may impact fertility but not specifically though PFO.
Mr and Mrs Smith each are heterozygotes for delta F508 mutation of the CFTR gene and are undergoing Preimplantation Genetic Diagnosis(PGD) to avoid transfer of embryos homozygous for delta F508. Mrs Smith who is 39, inquires about her increased of Down syndrome and asks if screening also can be undertaken for aneuploidy. Which of the following statements can you report to her about using fluorescence in situ hybridization (FISH) technologies for aneuploidy detection for Preimplantation Genetic Screening (PGS) ?
A. decreases Down syndrome miscarriages
B. decreases Down syndrome livebirths
C. increases implantation rates
D. removes the need for CVS or amniocentesis
E. has not yet shown any proven benefit
The correct answer is E. – Aneuploidy is known to increase as women age and theoretically screening the embryos of women of women of advanced maternal age prior to transfer should decrease their rate of aneuploid conceptions. This should indirectly increase their implantation rate, lower their miscarriage rate and increase their delivery rate. However, while initial studies with FISH were promising, randomized controlled trials found no benefit to screening embryos prior to transfer and even detriment to implantation rates. Advances in technology to allow application of aCGH to PGS may overcome these difficulties.
Mrs. Smith has an 11-week ultrasound with a fetus with a nuchal translucency measurement of 4.5 mm. Her diagnostic testing by chorionic villlus sampling (CVS) reveals 46, XY. At second trimester ultrasound, the risk is greatest for identification of anomalies in which of the following systems?
A. Cardiac
B. Central nervous system
C. Gastrointestinal
D. Genitourinary
E. Skeletal
The correct answer is A. – With increasing nuchal lucency in the first trimester the risk of a structural malformation being detected on the second trimester ultrasound increases. The association between cardiac anomaly and nuchal edema may be physiologic although there does not appear to be good correlation between type of cardiac defect and presence of increased edema. Among fetuses with trisomy 21, increased nuchal edema in the first trimester is not predictive of a second trimester cardiac anomaly despite the high prevalence of cardiac malformations in Down syndrome.
Among male causes of infertility, which of the following would be most likely to be encountered in the man with oligospermia?
A. Balanced translocation
B. Fragile X mutation
C. Delta F508 mutation
D. Sex chromosome aneuploidy
E. Sertoli cell only syndrome
The correct answer is A. – based on frequencies of infertility identified in each category, A (balanced translocation) would be most commonly encountered with oligospermia. Sex chromosome aneuploidy and Sertoli cell only syndrome are commonly associated with azoospermia; Delta F508 mutuation with obstructive azoospermia and CBAVD.
Mrs. Smith is scheduled for a chorionic villus sampling (CVS) at 11-weeks gestation as she and her husband are carriers of cystic fibrosis. They are aware of their 25% risk and are seeking early diagnosis. However, while she is aware of the risk of miscarriage associated with CVS, she also inquires as to which of the following complications have been associated with CVS?
A. Abruption
B. Hemangioma
C. Placenta previa
D. Preterm delivery
E. Preterm premature rupture of membranes
The correct answer is B. – Adverse pregnancy outcomes with regard to aberrant placentation, preterm labor or rupture of membranes have not been associated with CVS. However, concern has been raised as to the possible effects on the fetus and in particular most recently an increase in hemangiomas. This increased risk in hemangiomas appears to be concentrated in transcervical CVS and is not gestational age dependent (in contrast to the limb reduction abnormalities which were concentrated in the < 10 week CVS cases).
Among
in the man with non-obstructive azoospermia?
male causes of infertility, which of the following would be most likely to be encountered in the man with non-obstructive azoospermia?
A. Balanced translocation
B. Fragile X premutation
C. Delta F508 mutation
D. Sertoli cell only syndrome
E. Sex chromosome aneuploidy
The correct answer is E. – balanced translocation is associated with oligospermia; cystic fibrosis mutation associated with obstructive azoospermia (CBAVD) and sex chromosome aneuploidy associated with non-obstructive azoospermia. Sertolic cell only syndrome is a rare cause of azoospermia. Fragile X is not associated with male infertility.
Among male causes of infertility, which of the following would be most likely to be encountered in the man with obstructive azoospermia?
A. Balanced translocation
B. DAZ deletion
C. Delta F508 mutation
D. Fragile X premutation
E. Sex chromosome aneuploidy
The correct answer is C. - balanced translocation is associated with oligospermia; cystic fibrosis mutation associated with obstructive azoospermia (CBAVD) and sex chromosome aneuploidy associated with non-obstructive azoospermia. DAZ deletion is a cause of azoospermia, fragile X premutation is not a associated with infertility in the male,
If a fetus has a nuchal translucency increased to 2 standard deviations at 11-14 weeks, which of the karyotype results is the most likely to be found on amniocentesis?
A. 45, X
B. 45, X/46,XX
C. 46,XX
D. 47,XX, +18
E. 47, XX, +21
The correct answer is C. – as a screening test, an enlarged NL at the second standard deviation increases the relative risk for aneuplopidy but will be encountered most commonly in chromosomally normal pregnancies.
Mrs Jones is 35-years-old and has an amniocentesis for an increased risk of Down syndrome based on her maternal serum screening. The ultrasound at the time of the amniocentesis was unremarkable without structural abnormalities noted in the fetus, nor ultrasound markers for Down syndrome. The amniotic fluid was normal and the placenta was posterior without hematomas noted. Two days following the amniocentesis she is diagnosed with premature rupture of membranes. Which of the following outcomes are you going to counsel her is the most likely?
A. Chorioamnionitis
B. Chorionamnion separation
C. Fetal demise
D. Miscarriage
E. Reaccumulation of amniotic fluid
The correct answer is E. – Premature rupture of membranes following amniocentesis occurs in approximately 1% of cases. Reaccumulation of the amniotic fluid occurs in > 90% of patients though on average takes 3 weeks. The outcomes are generally favorable which is in contrast to spontaneous rupture of membranes in the second trimester which is associated with fetal demise, miscarriage and chorioamnionitis.
