History:

A 36-year-old gravida 3 para 2 woman had an uneventful prenatal course, but she received no prenatal care until the third trimester. An ultrasound at 32 weeks gestation suggested that the developing fetus had polydactyly, a cleft lip and palate, and a ventricular septal defect. The baby was born prematurely at 36 weeks. Multiple anomalies were noted at birth. The placenta was normal. Apgar scores were 1 at 1 minute and 3 at 5 minutes. The baby was initially intubated because of poor respiratory effort, and an umbilical vein catheter was placed. However, after discussion with the parents regarding the prognosis, ventilatory support was discontinued and the baby expired 2 hours after birth. An autopsy was performed to determine the findings for genetic counseling.

The major pathologic findings pictured in the images include a bilateral cleft lip, two scalp defects, and polydactyly (six fingers). The sixth finger is almost a tag. Internal examination reveals a diaphragmatic hernia because of a missing left leaf of the diaphragm. The heart and lungs are displaced to the right and superiorly because of the liver, spleen, and bowel herniating upward through the defect.

The karyotype shows a 47 XX, +13 pattern.

Questions:

1. What genetic syndrome is represented here?

The spectrum of defects is consistent with a trisomy 13. This was confirmed with karyotyping of fetal cells, which showed an extra chromosome 13. Additional associated findings included cardiac defects with an atrial septal defect and a ventricular septal defect, a Meckel's diverticulum, and a two vessel umbilical cord.

2. How do the internal autopsy findings explain the clinical presentation?

The lungs were compressed by the herniated tissue and were hypoplastic. The hypoplastic lungs could not be ventilated. Diaphragmatic hernia can be seen as an isolated finding, but is more common in association with other congenital anomalies. Remember that if one anomaly is present, others are more likely.

Most gross congenital anomalies (many of which are incidental or unimportant--Meckel's diverticulum or accessory spleen) are not associated with a defined karyotypic abnormality (at least with current methods of testing). Remember that most chromosomal abnormalities result in early spontaneous abortion and many (such as trisomy 16 or tetraploidy) are almost never seen in liveborn babies. However, if a mother has a history of having had multiple miscarriages, stillbirths, or babies with anomalies (or if there is a family history of anomalies) then chromosome analysis becomes more important.



3. What do you tell the parents when prenatal testing yields a 47, XX, +13 karyotype?

Trisomy 13 (and 18) are best described as "incompatible with life." Most die in utero and are not liveborn. Those that are liveborn will survive only a short time, at least in part because of prior agreement by the parents and doctors not to extend the life of these babies via interventions, as their problems (mental and physical) are so great. For medical students, that is an important lesson, as it is really an unspoken and unrecognized fact in many medical situations. If someone wanted to keep a newborn alive with trisomy 13 or 18, or any of many other extremely rare and grave diseases, it might be possible to "break the record" (have the longest lived baby with some terrible disease). Fortunately very few parents make that choice for their babies.

That's the tough part to admit, for both doctors and ethicists. Such advice would usually be couched thus: "we don't want your baby to suffer, so we should focus all our efforts on keeping the baby comfortable, and not in pain, but not on trying to prolong life--or to prolong dying." This may sound very cold, but it can help parents to know that other parents have gone through this, and they can join support groups so they don't feel like no one knows what they are going through.

Overall, most grave conditions such as trisomies are rare, but there are more parents out there who have had a tragedy somewhere in their reproductive years than you might realize. Miscarriages are very common, of course, and sometimes they occur in the second or third trimester. When you add those to first trimester losses and to the various causes of death in the perinatal period, there are many couples who have been through some type of loss. Once a couple admits to such an experience they will often find others who want to share similar stories.

With any live birth, and even with fetuses in the 2nd and 3rd trimesters, hospitals (via the labor & delivery service) have standard procedures in place to produce not only the standard documentation of the process (birth certificate for live births, hand/foot prints) but also additional keepsakes including photographs and a gown for the baby to wear. The parents will usually get a keepsake box with these items. This helps them to remember their baby and pay it the respect it deserves. They may not specifically ask for it or want to take it right away, but you can offer to keep it and then give it to them at a follow up visit (and that can even be at the first anniversary of the baby's birth). Generally, within 6 months of the loss, the parents will want everything they can have related to the loss.

4. What if the karyotype revealed a mosaic 47, XX +18 / 46, XX karyotype?

Some cases are not so clear cut, particularly when karyotyping reveals a "mosaic" condition in which some, but not all, the babyÕs cells have the chromosomal defect. A mosaic condition is generally less severe than the complete chromosomal condition.