Prenatal Genetics (TRANSFERRED) Flashcards
Reference: Genetics residents in-training examination - March 2020 (Spring 2020)
A 29-year-old woman is referred for nuchal translucency at 3.6 mm. A non-invasive prenatal screening (NIPT) by analysis of fetal DNA in maternal blood revealed a low risk for trisomy 13, trisomy 18, and trisomy 21. The fetal ultrasound at 15 weeks showed an enlarged placenta, and intrauterine growth retardation (IUGR) with an estimated fetal weight at the 5th percentile.
Amniocentesis is performed in order to confirm the diagnosis. What is the expected result of the following diagnostic tests:
- QF-PCR
- karyotype
- array CGH
- SNP-array
Triploidy on QF-PCR and on the karyotype; array-CGH will be normal, but SNP-array will show the triploidy.
Reference: Genetics residents in-training examination - March 2020 (Spring 2020)
Cite 3 reasons for the absence of result on non-invasive prenatal screening by analysis of fetal DNA in maternal blood.
- Gestational age < 10 weeks at blood collection
- Obesity
- Aneuploidy types trisomy 13, 18, and triploidy
Reference: Genetics residents in-training examination - March 2020 (Spring 2020)
A 39-year-old woman, G1P0, is referred for fetal echogenic bowel. She and her partner are French Canadian. A non-invasive prenatal screening by analysis of fetal DNA in maternal blood (NIPT) revealed a low risk for trisomy 13, trisomy 18, and trisomy 21. A fetal ultrasound at 22 weeks showed isolated echogenic bowel and an estimated fetal weight at the 60th percentile.
Name 5 causes of fetal echogenic bowel.
For each cause, estimate the proportion of echogenic bowel explained by it.
For each cause, explain what test you would offer to this couple or explain why you would not investigate for this cause in their specific case.
- Trisomy 21- around 1%: no test to propose because the NIPT is low risk
- Infection- around 2-3 %:TORCH screening
- FKP- around 2-3 %: Screening for cystic fibrosis carrier for both partners
- Intestinal anomaly (volvulus, Hischsprung…)-very rare in absence of dilatation: ultrasound follow-up in 2-3 weeks
- IUGR- around 5%: more association than etiology; here the EFW is normal.
Reference: Genetics residents in-training examination – Fall 2020
A. What are the commonly accepted cutoff of measurements for the Nuchal translucency for :
a. The 95th centile (give measurement in mm)
b. The 99th centile (give measurement in mm)
B. What are the usual weeks of Gestation when NT is measured? (between what and what weeks gestation)
C. What is the difference between a large NT and a first trimester cystic hygroma?
D. Name four common fetal conditions or findings associated with NT ≥ 99th centile, and at least one investigation that you would offer for each cause.
E. A patient with an increased NT (≥ 99th centile) declined the offer of any additional genetic testing/screening when seen at 15 weeks. What specifically do you recommend to her care provider?
A.
a) ≥3.00 mm
b) ≥ 3.5 mm
B.
Usually accepted between 10-14 , though could accept province specific dates (e.g. 11 – 13). First trimester not specific enough.
C.
Increased NT is an abnormal accumulation of fluid behind the fetal neck without septations
Cystic hygroma refers to septated cystic structure located in the occipitocervical region, but can extend beyond this.
D.
- Aneuploidy; NIPT/QFPCR/karyotype
- Chromosomal; microarray
- Single gene; Noonan single gene panel/fetal exome
- Heart defect/congenital diaphragmatic hernia/ skeletal dysplasia/other major anomaly; level II/detailed morphology scan at 18-22 wks
E.
Fetal ECHO, after 18 weeks along with detailed anatomy scan.
Reference: Genetics residents in-training examination – Fall 2020
A 40-year-old patient is referred to their local Medical Genetics department after a no-result Non-Invasive Prenatal Testing (NIPT)/ Non-Invasive Prenatal Screen (NIPS).
Name two maternal and two fetal/placental causes for a no-result.
Maternal: Low fetal fraction - Weight greater than 235lb
Maternal CNV/mosaicism
Unmatching maternal/fetal DNA patterns – e.g. egg donor, maternal bone marrow transplant
Fetal: Low fetal fraction (early gestational age, fetal demise, dating error),
Aneuploidy (placental, fetal or both)
Fetal mosaicism
Reference: Genetics residents in-training examination – Fall 2020
A healthy 30 year old woman has an anatomy scan at 18 weeks’ gestation. The scan shows an isolated echogenic intracardiac focus. First trimester screening yielded a low risk result and all previous investigations were unremarkable.
Please explain the impact of the finding on the aneuploidy risk of the patient and the most reasonable next step in addressing this risk.
No impact. Reassurance.
Reference: Genetics residents in-training examination – Spring 2021
a) Define renal hypoplasia (2)
b) What are the two main forms of this condition and how do they differ with respect to age of onset, presentation, and laterality? (6)
a) A congenitally small kidney less than 50% of the expected weight for age (1), but without abnormal parenchymal differentiation (1) i.e. not renal dysplasia, or evidence of acquired disease.
b) Simple hypoplasia [nephron number normal but mass reduced] (1) – 75% unilateral (0.5), usually asymptomatic (1).
Oligomeganephronia [nephron number reduced with compensatory increased nephron size and hyperfiltration] (1) – bilateral (0.5), presents in the first 2-3 years of life (1) with vomiting, dehydration, growth retardation (1).
Reference: Genetics residents in-training examination – Spring 2021
A pregnant woman has nuchal translucency and non-invasive prenatal screening at 13 weeks gestation with normal results. The ultrasound examination at this time indicates a singleton pregnancy with apparently normal fetal anatomy. A sample drawn for maternal serum alpha fetoprotein (MSAFP) screening at 17 weeks shows a significantly elevated level. She undergoes a detailed fetal assessment and no fetal anomalies that would explain the high MASFP level are found.
a) Document two possible conditions that can account for unexplained elevations in MSAFP. (2)
b) Identify four maternal, fetal or neonatal complications that such pregnancies are at significantly increased risk for. (4)
a) Maternal tumour e.g. hepatocellular carcinoma, ovarian mixed-germ cell carcinoma
Choriocarcinoma
Autosomal dominant hereditary persistence of AFP (OMIM 615970) benign
Fetus papyraceous/vanishing twin
Fetal nephrotic syndrome
Occult placental bleed
b) Preeclampsia, fetal growth restriction, intrauterine fetal death (SA and SB), low birth weight, placental abruption, preterm birth (1 mark each)
References
Hu JL et al. Pregnancy outcomes of women with elevated second-trimester maternal serum alpha-fetoprotein. Taiwan J Obstet Gynecol. 2020 Jan;59(1):73-78. PMID: 32039804.
Bartkute K et al. Pregnancy outcomes regarding maternal serum AFP value in second trimester screening. J Perinat Med. 2017 Oct 26;45(7):817-820. PMID: 27771626.
Tancrède S et al. Mid-trimester maternal serum AFP and hCG as markers of preterm and term adverse pregnancy outcomes. J Obstet Gynaecol Can. 2015 Feb;37(2):111-6. PMID: 25767942.
Reference: Genetics residents in-training examination – Spring 2021
Omphalocele is an abdominal wall defect that occurs in ~1 in 4000 births. Approximately 2/3 of cases have additional anomalies including chromosomal, cardiac and neural tube defects.
a) What is the most commonest chromosomal disorder associated with omphalocele? (1)
b) Name one condition in which omphalocele is associated with other body wall defects (1)
c) A women presents for a fetal assessment at 18 weeks gestation to evaluate fetal structural anomalies. A small omphalocele is identified, but careful examination reveals no other malformations and a fetal echocardiogram is normal. She has not had previous screening in this pregnancy, but consents to an amniocentesis. If your centre has limited resources for molecular investigations on the amniotic fluid sample which two tests are the most likely to identify if this fetus has an underlying genetic condition? (2)
a) Trisomy 18
b) One of: Pentalogy of Cantrell, Limb-body-wall complex, OEIS/cloacal exstrophy
c) Anomalies on QFPCR or other form of RAD are rare in apparently isolated omphalocele, but have been reported. The commonest is trisomy 18 in ~5%. This mark can also be given if microarray is requested although may not be considered as fiscally responsible as the yield is not much higher than RAD. (1)
The highest yield is targeted Beckwith-Weeidemann screening, which occurs in up to 20% of isolated cases. Macroglossia and macrosomia can occur prenatally in apparently isolated cases, but not until later in pregnancy. BWS testing is especially indicated in pregnancies conceived with ART.(1)
Reference: Genetics residents in-training examination – Spring 2021
a) Define the acronyms PGT-A and PGT-M (2)
b) Identify which of the following statements are true and which are false. (3)
i) PGT-A is a screening test. (True / False)
ii) Multiple marker screening for trisomies 21 and 18 is recommended for pregnancies conceived after PGT-A. (True / False)
iii) In pregnancies conceived after mosaic embryo transfer, CVS is recommended as the preferred option for prenatal diagnosis. (True / False)
a)
preimplantation genetic testing for aneuploidy = PGT-A
preimplantation genetic testing for monogenic disorders = PGT-M
b)
i) TRUE ii) FALSE iii) FALSE
Reference: Genetics residents in-training examination – Spring 2021
See the supplemental file for 3 electropherograms from QF-PCR rapid aneuploidy detection and state the depicted karyotype in standard ISCN nomenclature. (3)
a) 47,XY,+21. b) 46,XX. C) 69,XXX - 1 mark each
