The comments and questions below recently left by one of our readers are interesting because they raise the possibility (again) that the congenital conditions with which all three of her children (and perhaps even the one she is currently carrying) were born could be related to a single genetic defect. It may be a bit of a ‘stretch’ on my part, but if my readers didn’t challenge me to think, then you all would not have to put up with my vivid imagination!
• At Thu Mar 06, 10:34:00 PM 2008, Anonymous said…
Dear Dr. T:
I am 40 years old and am 16 weeks pregnant with my 4th child. I am scheduled for a level 2 ultrasound and consult with a perinatologist tomorrow. A couple of weeks ago, I thought I was 12 weeks based on my last cycle. However, I was measuring larger so I had an ultrasound to determine dates. The ultrasound showed I was 14 weeks and they also found a large cystic hygroma with edema (hydrops) of the skin. I don't think they told me the exact measurement of the cystic hygroma.
My first pregnancy was uncomplicated. My first son developed Fifth’s disease (parvovirus B19) when I was pregnant with my second son which, I was told caused encephalitis of the brain. They also found a cyst on his brain which later disappeared. I was given a 50% change of his survival. My son is now 13 years old. He was born with a sebaceous cyst on the side of his nose and has been diagnosed with ADHD. I also have a 2 1/2 yr old daughter who was born with a sebaceous cyst on the back of her head. I am pretty sure she has ADHD as well. Both are very smart. I had gestational diabetes with all three pregnancies. I am also Rh-negative. My questions are:
1) Do you think that there could be any association between the sebaceous cysts of my other children and the cystic hygroma of the baby I am now carrying?
2) I think my daughter had Fifth's disease during this pregnancy. Is it possible to get parvovirus B19 more than once? I'm wondering if the possible exposure to parvovirus B19 caused the cystic hygroma and hydrops?
3) Is it possible that my RH negative condiditon caused the hydrops?
4) Finally, I have been doing a great deal of reading about this condition and researched natural vitamin and herbal supplements that reduce edema. I have found that they have been successful doing clinical studies on pregnant women in Europe with no ill effects on the babies using some of the same vitamin/herbal supplements to reduce hemorrhoids. The products I am considering taking are supposed to reduce or eliminate edema and strengthen veins. They are Diosmin & Hesperidin (Citris bioflavanoid), Horse Chestnut extract, and Butcher's Broom Extract. I found documentation from the FDA that deemed the bioflavanoids safe during pregnancy in the U.S. However the studies on the herbals were done in Europe and the Netherlands. I would greatly appreciate your comments and/or advice on all of my questions. I have also been taking dandelion leaf extract to try to reduce the hydrops. I was told it was perfectly safe during pregnancy. I am so surprised that no one is trying to do anything to reduce edema (hydrops) since that seems to be the biggest concern and is associated with increased risk of fetal of demise. Thank you so much!!
• At Sat Mar 08, 04:33:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Mar 6: Let me answer the questions as best I can in the order you asked them:
1) The cystic hygroma is probably not related to the sebaceous cysts of your other children. It is much more likely at your age that the baby with the cystic hygroma has a chromosomal abnormality. As you point out, the hydrops is not good and often is associated with loss of the baby in utero. If the baby turns out to be chromosomally normal, then it could be related to the genetic condition I will discuss below.
In that regard, the issue of the "sebaceous cysts" in two of your children and, perhaps, even the intracranial “cyst” in your first child is interesting in its own right. Could these all be related? Congenital sebaceous cysts are unusual. In my review of the literature, I did find an association between congenital sebaceous cysts and a condition called 'familial adenomatous polyposis (FAP)' (Bisgaard, et al., Am J Genet A 2006;140:200-4 and Cross, et al., J Med Genet 1992;29:175-9) and Gardner’s syndrome, which is a phenotypic variant of FAP. These conditions are caused by mutations of the APC (adenomatous polyposis coli) gene found on the short arm of chromosome 5 (5q21). The normal APC gene encodes a tumor suppressor gene product.
Gardner’s syndrome is an autosomal dominant condition (i.e., it only takes one bad gene mutation rather than two to cause disease) that causes familial (hereditary) polyposis of the colon and rectum, osteomas (bone tumors), and cutaneous epidermoid (sebaceous) cysts. Colon cancer will develop in virtually 100% of individuals with this condition during their lifetimes (usually in the third and fourth decades of life) unless the colon is removed prophylactically. Individuals with FAP can also develop polyps of the upper gastrointestinal tract, dermoid cysts, desmoid tumors, congenital hypertrophy of the retinal pigment epithelium, maxillary (jaw bone) disorders and dental abnormalities (Chimenos-Kustner, et al., Med Oral Patol Oral Cir Bucal 2005;10:402-9). One article even describes a case of a cortisol-producing tumor (causing Cushing’s syndrome) in an adrenal gland of a 36 year old woman with Gardner’s syndrome (Beuschlein, et al., Endocr Res 200;26:783-90). What I found most fascinating is that individual’s with Gardner’s syndrome are also at risk for a variety of intracranial solid and cystic tumors (Goodin, et al., Pediatr Blood Cancer 2008;50:409-12).
You might want to discuss this possibility with a good genetic counselor to review your family history and to see if there are any genetic or other diagnostic studies necessary that should be done to determine if the children have this condition.
2) I doubt you would be at risk with this pregnancy if your daughter had Fifth's disease. You should be immune to it now and it is unusual to get that twice.
3) I very much doubt the current baby's problems are at all related to your Rh-negative status. Even if you are ‘isoimmunized’ (had antibodies against Rh), which your doctors could tell you by now, that usually does not cause problems with babies until later in midtrimester at the earliest.
4) The edema is not just there as a disease entity in and of itself. Most of the time it is the result of fetal heart failure and there can be lots of reasons for that (.e.g., structural malformations of the heart, fetal arrhythmias, and chromosomal abnormalities or metabolic abnormalities resulting in dysfunction of the heart). Hydrops in the setting of cystic hygromas has a fetal loss rate that approaches 100%. I would be very cautious of any herbal preparations to try to treat this yourself. One of the problems with over-the-counter herbal preparations is that they are not standardized, may vary from batch to batch and from company to company, and may contain products and impurities other than those listed on the bottle. Most of the ones you have mentioned should not have a deleterious effect on the pregnancy, but again, you may not really be sure what it is you are taking into your body.
Best wishes to you and thank you for some excellent questions! Let us know how things turn out and what you learn about the other children who were born with the sebaceous cysts! Dr T