Embryologic Correlations

CASE 8: Endocardial Cushion Defect

Clinical History:

A 19-year-old woman is G3 P2 and in the 19th week of pregnancy by dates. A serum triple screen shows a low unconjugated estriol (uE3) with high HCG and low AFP. The fetal size equivalent is 17.5 weeks. The head is normal in size, but there is increased nuchal thickness. The extremities appear normal. The heart has what appears to be an endocardial cushion defect with flow of blood between all of the heart chambers. The amniotic fluid index (AFI) is increased. In the abdomen is a "double bubble" sign.

  1. What embryologic problem is seen in the thorax?

  2. The endocardial cushions of the atrioventricular canal divide the canal into right and left orifices and participate in the formation of the membranous interventricular septum (along with the truncoconal ridges) and the closure of the ostium primum. This separates the heart into four chambers. Complete absence of this process results in a two chamber heart with a common atrioventricular valve. Lack of formation of the membranous interventricular septum results in a ventricular septal defect. If the atrial septum (primum or secundum) does not form, then an atrial septal defect will result.

  3. What is the condition called with a high AFI and how is it most likely produced in this case?

  4. Increased amniotic fluid volume is called polyhydramnios. Amniotic fluid is formed from fetal urine. A urinary tract problem will result in decreased amniotic fluid - oligohydramnios. Amniotic fluid is swallowed and absorbed in the fetal gastrointestinal tract. An obstruction in the GI tract will lead to polyhydramnios. The most likely obstruction with trisomy 21 is duodenal atresia, which produces the "double bubble" sign on ultrasound (one stomach bubble and one duodenal bubble).

  5. Is a chromosomal abnormality likely to be present?

  6. Yes. The findings are highly suggestive of trisomy 21 (Down syndrome). Most cases of trisomy 21 will be +21, but about 5% will have a "Robertsonian" translocation, typically 46, XY +(14;21) in a male fetus, with a balanced translocation present in one parent.

  7. What would a "FISH" analysis show?

  8. Flourescence in-situ hybridization (FISH) with a probe to a portion of chromosome 21 will probably show three signals in each fetal cell. FISH is more rapid than karyotyping. FISH is very useful to find translocations.

  9. What are possible outcomes?

  10. Most chromosomal abnormalities result in fetal loss - abortion (prior to 20 weeks) or stillbirth. A few cases of trisomy 21 can be liveborn. Multiple congenital anomalies may preclude survival in infancy unless intervention is undertaken - cardiac surgery in this case.

  11. What is the recurrence risk?

  12. The majority of cases are sporadic. In cases where one parent has a balanced translocation, half of fetuses will be non-viable, a third will have trisomy 21, and a sixth will be normal.

    The risk for nondisjunctional events in meiosis is age-related. The risk goes up dramatically after maternal age of 40. However, there are not that many pregnancies in that age group. Hence, most of the cases of Down syndrome occur in younger women just because there are far more pregnancies in that group.