Case Discussion - A Woman Presenting for Preconceptional Counseling ...

Mrs B, 24 years old had a previous baby with Down syndrome who is now one year old.She is desirous of further childbearing but is apprehensive about similar problem in the next baby and has come for preconceptional counseling. The karyotype of the affected child showed Trisomy 21 (47,XY).

Approach to the Case: 

Points to be asked in History
• Age of the mother at delivery
• Period of gestation at which the pregnancy was registered
• First trimester scan for nuchal translucency
• Whether first or second trimester screening was done
• Second trimester anomaly scan
• Pregnancy outcome: Miscarriage, stillborn or live born

She mentions that her first pregnancy was a spontaneous conception. She sought antenatal care at 20 weeks of pregnancy. She had a term delivery at a hospital of a small for gestational age baby. The baby had mongoloid facies and a ventricular septal defect was diagnosed. The baby had delayed milestones and on investigations the baby was diagnosed with Trisomy 21.

What recurrence risk would you attribute to this lady?
Down’s syndrome cases result from nondisjunction, translocation or mosaic. With a pregnancy complicated by trisomy 21 from nondisjunction, the woman has 1% risk of having a pregnancy with trisomy in subsequent pregnancy. This risk pertains unless her age related risk exceeds it. Because of this risk, she would be offered invasive prenatal diagnosis. Parental karyotype is not indicated in this
couple.

What is the incidence of Down syndrome in general population?
Down’s syndrome occurs in 1 in 800 to 1 in 1000 newborns



What is the indication of parental karyotype in cases of Down syndrome?
When a fetus or child is found to have a translocation trisomy, chromosomal studies of both parents should be performed. If neither parent is a carrier and the translocation occurred spontaneously, the recurrence risk is extremely low. In one third cases one parent will be a carrier. Other relatives can also be carriers and efforts should be made to identify all adult translocation carriers in a family so that they can be alerted to possible risks to future offspring. This is sometimes referred to as translocation tracing or chasing.

Now the woman in the above scenario reports to you at 8 weeks pregnancy.

What is your plan of management in the current pregnancy?
Since the recurrence in this pregnancy is about 1%, the women will be directly offered invasive testing with chorionic villous sampling to ascertain the chromosomal configuration of the fetus. In such patients there is no role of serum screening or combined screening. If she reports later than 14 weeks she is offered prenatal diagnosis with amniocentesis.

What are the indications of invasive prenatal testing?
1. Maternal age > 35 years
2. Previous offspring with aneuploidy.
3. Multiple or major congenital malformations on ultrasonography
4. Positive screening test.
5. Parental aneuploidy.
6. Intracytoplasmic sperm injection: there is increased risk of (1%) sex chromosomal abnormalities in pregnancies established by ICSI.
7. Recurrent spontaneous miscarriages.
8. Family history of single gene defects.
9. Structural chromosomal rearrangements.
a. Either parent with Robertsonian translocations
b. Parental reciprocal translocations: mode of ascertainment is very important. If a balanced reciprocal translocation is ascertained through an unbalanced child or another liveborn relative, the likelihood of unbalanced live borns is approximately 20%. If balanced translocation is ascertained through a history of repeated miscarriage, the risk for an abnormal liveborn is much lower.