Thursday, May 14, 2009

Genetics: Looking for Clues in This and Other Cases

Certainly no genetic cause for fatal umbilical cord abnormalies has been found. That may be because there isn't one. Or it may be because so very little research has been done. The question is whether the genetic code responsible for the formation and development of the umbilical cord is itself flawed, or whether the genetic code is fine but the instructions can't be carried out properly because of other unknown factors.

The first two case studies we've looked at previously offer little information. The karyotypes (a test to identify and evaluate the size, shape, and number of chromosomes in a sample of cells) of the babies are normal, except one baby with a deletion in 3 out of 15 cells tested, which is not thought to be significant in this case.

The mother who lost 4 out of 8 babies to cord torsion said there is no family history of such problems and no abnormalities were discovered on karyotypes of the lost babies.

In my own case, the karyotypes on both babies came back normal, except for an inversion in one of Jeremiah's chromosomes:

This male karyotype carries a pericentric inversion of the heterochromatic region of one chromosome 9. This inversion written inv(9)(p12q13)) is an apparently normal chromosomal variation (polymorphism) found in approximately 2% of the general population. A large study carried out by Hsu et al. (1987) did not find any deleterious phenotypic or clinical effect of this chromosomal polymorphism, nor of any apparent association with fetal loss.

When my husband and I had karyotypes done on us, we found I have this same inversion. Our second lost baby, Miles, did not have it. Karyotyping is of very limited use in finding a possible genetic cause for such losses because it will only detect large changes in chromosome structure - large deletions, insertions, translocations, inversions, or duplications of thousands of base pairs. They will not detect single nucleotide changes, deletions, or insertions. The majority of genetic diseases are caused by single (or fewer than 10) base pair changes. It would be fascinating if DNA from babies such as ours could be analyzed with the technique written about here (read under "Completing the Picture").

In our case, we have wondered about a genetic link because of the circumstances of my husband's birth. He was born at term weighing only 5 lb. 0 oz. and had a small placenta and thin cord. Twenty-seven years later, our son David was born at term weighing only 5 lb. 0 oz. and with a small placenta and thin cord, exactly like dad. ALL of our four babies have had placenta/cord issues, with a 50% survival rate. When our daughter Tania was born, the doctor mentioned that her placenta was unusual because it had "2 sacs". She was not low-birthweight like her brother, but was still smaller than average at term, weighing in at 6 lb. 3 oz. Unfortunately, the placentas and cords from our two live births did not get sent to pathology. And of course our last two pregnancies were losses, Jeremiah from cord hypercoiling and Miles from cord stricture.

Since I've had a long history of gynecological problems (endo, cysts, etc.) it would be easy to conclude that our losses are my "fault", even though none of my problems are associated with late losses. I do wonder,though, if the problems my hubby had at birth were the result of a random and usually deadly genetic mutation affecting the cord/placenta - and now his random genetic mutation is passed on to our offspring as an inherited genetic mutation.

It should be noted that there have been no other cases of fetal loss or cord/placenta abnormality in either side of the family. My husband has four sibling and I have seven siblings who were all born without any issues similar to ours. Our siblings' children have all likewise been unaffected.

These days, of course, there are ways to get around a genetic flaw without jumping straight to adoption. In our case, if we knew the problem was genetic and we knew it came from my husband, I suppose we might go for a sperm donor because it's so much easier and cheaper than adoption, there are no strings attached, we would get to experience the pregnancy and birth, and the child would be 1/2 ours genetically.

But if we knew the genetic flaw was mine, then we'd be out of luck. For my part, I'm all for trying an egg donor even now with all the uncertainties of our case, but the price tag (estimated $30,000) puts this option way beyond our reach.

Another option for bypassing a genetic defect is embryo adoption, where "leftover" embryos from other couples' IVF treatment are given for "adoption" rather than thrown away. This option is cheaper and faster than adoption, the couple gets to experience pregnancy and birth, and avoid much of the legal and financial drama of a regular full-term adoption. The price tag (estimated $7000-8000) is a bargain if it works, compared to some other options such as using an egg donor, a surrogate, or doing an international adoption. But in my opinion it's still too much of a gamble unless you know you can bypass a genetic flaw in this way. Still, it doesn't hurt to be on the clinic's donor embryo list because it can take years before the option even becomes available. Who knows what our situation will be then?

So there are options, but even if mom & dad don't have religious, ethical, or moral qualms about bringing a 3rd, or even 4th party's DNA into the family, the resulting child may - and so might other siblings and the extended family. Of course, there's always the option of keeping the whole thing secret, but that also would bring up lots of issues.

The decision for us, at least for now, is that genetic tinkering will not be pursued. Although a good case can be made that our problem may in fact be genetic, we don't know that, so messing with our child's DNA would be a bizarre science experiment which, even if it went well and resulted in a live child, has the potential to put some very unique strains on our marriage and family.

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