What is Aneuploidy?
Tuesday, November 28, 2006
Kenneth F. Trofatter, Jr., MD, PhD
Chromosomes contain the thousands of genes that orchestrate our growth, development, and biochemical functions. The normal human chromosomal complement is 46, or 23 pairs (22 pairs of ‘autosomes’ plus 2 ‘sex chromosomes’) with each parent contributing one chromosome per pair to the final genetic constitution of the baby. When a baby has too few or too many chromosomes, or even a small portion of a chromosome missing or extra, the baby is said to have a chromosomal abnormality, or aneuploidy. Most babies with an unbalanced amount of chromosomal material miscarry during the first trimester of pregnancy. Indeed, chromosomal abnormalities account for more than 50% of all spontaneous miscarriages in women who previously have had uncomplicated pregnancies. (Interestingly, they are NOT the most common cause of miscarriages in first pregnancies, a topic for a future post). Some babies with aneuploidy may be lost later in pregnancy and some will survive to be born.
There are a variety of ways by which a baby can end up with aneuploidy, and detailing all of these is not necessary for this post; however, the one that results in conditions with which the most people are familiar is an event called ‘nondisjunction.’ During the final step in gamete (egg or sperm) production, the 23 pairs of chromosomes must line up and then separate so that one of each pair is incorporated into the sperm or egg (oocyte), producing two gametes each with 23 chromosomes. When nondisjunction occurs, both chromosomes in a pair move together, resulting in one gamete with 24 chromosomes and one with 22 chromosomes. If one of these unbalanced gametes participates in the production of an embryo, assuming the correct number of 23 is contributed by the other parent, the baby will end up with a total of either 47 chromosomes or 45 chromosomes and be aneuploid, in this case with one entirely extra or too few chromosomes. Again, most of the time when this happens, the result is lethal, and the pregnancy ends spontaneously in miscarriage.
Examples of aneuploid babies that may survive through delivery with which many of you may be more or less familiar are an extra chromosome 21 (trisomy 21, or Down syndrome), an extra chromosome 18 (trisomy 18) or, rarely, an extra chromosome 13 (trisomy 13). Babies may also be born with missing or extra sex (X and Y) chromosomes (a normal female is XX and a normal male is XY). Common examples of this are, respectively, Turner’s syndrome (45 XO), affecting 1 in 2500 girls, and Klinefelter’s syndrome (47 XXY), affecting about 1 in 600 to 800 boys. Even most babies with any these chromosomal abnormalities are lost early in pregnancy.
Reasons for nondisjunction are poorly understood, but it is the event that is associated with increasing risk with increasing parental (especially maternal) age, and it is also the most common cause of aneuploidy at any age. In the case of Down syndrome, for example, the risk of delivering a baby with trisomy 21 is about 1 in 1250 for women at age 25, 1 in 1000 at age 30, 1 in 350 at age 35, 1 in 100 at age 40, and 1 in 25 at age 45. Risk for delivering a baby with any chromosomal abnormality is more than twice that for Down syndrome at any given age, i.e., 1 in 178 at age 35, 1 in 63 at age 40 and 1 in 18 at age 45. Because chromosomally abnormal babies can be lost throughout pregnancy, the chance of finding an aneuploid fetus is far greater earlier in pregnancy than at the time of delivery. For example, at age 35, the first trimester risk of finding a baby with trisomy 21 is 1 in 141 and in midtrimester it is only 1 in 270.
Discussions related to aneuploidy risks have become a daily routine in my practice because the trend over the past 30 years has been to delay childbearing until later in life. Data from the National Center for Health Statistics complied in 2002 demonstrated a drop in teenage birth rates to 43 births per 1000 (aged 15-19), a drop of 30% over the 10 year period from 1991; during the same time, birth rates for women aged 35-39 years increased to 41.4 per 1000, and for women aged 40-44, rose to 8.3 per 1000. These are the highest rates for women in these age categories ever recorded in the U.S. and the trend up seems to be continuing. So, in my next post, I will address issues related to aneuploidy screening….
12 Comments:
At Mon Apr 16, 12:47:00 PM 2007,
Anonymous said…
hi there doctor..my baby is in the hospital now with a working dx of cystic hygroma vs. hemangioma..the health team plan to aspirate the"tumor" which is located originally in the cheek but is now down in the left lateral neck region..the mass usually was tender/soft but my son got high fever (up to 39.5 C, the soft mass became hard, and there was redness, that's why i brought him to the hospital..antibiotics was started and right now, im waiting for the result of blood C/S..my question is, based on your knowledge,expertise and experience do you think it is such a good idea if i will give consent to the aspiration?..or rather, what good will it give if i give consent to this action?..advantages?.disadvatages?..im looking forward to your response through an article, is suppose, if possible, the soonest time..thank you and im so happy i found this site..
At Thu Apr 26, 06:43:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
I am not sure what this 'mass' is, but from what you describe, there is a high likelihood that this is now accompanied by inflammation/infection. There is an old adage in medicine (that holds to this day) that the treatment of an 'abscess' is first and foremost DRAINAGE. Therefore, my advice, purely based on what you have told me, is that you DO consent to the procedure, potentially, for BOTH therapeutic and diagnostic indications, regardless of the presumptive diagnoses of either cystic hygroma or hemangioma! Best wishes and thanks for reading.
At Sat Jun 09, 09:10:00 AM 2007,
Anonymous said…
Hi There
My name is Laura and i am 24 years old. Me and my husband went for our first 12 week scan a couple of days ago and to our shock we were told that our unvorn child has a cystic hygroma, which we are told is fluid underneath the skin at the back of the babies neck mesuring 6mm.
We are devasted at this new because we are told the outlook is not good. It is our first pregnancy and it has taken us so long to get pregnant due to my poly cystic ovaries, it just makes it so much harder to deal with.
We decided to have a cvs which is similar to amnio centisis (hope thats spelt right). They drew some fluid from the placenta i think which they are now going to test. We should have the test results for downs, turners and edwards syndrome by wed 13th june. We are praying that they will come back clear. They are then going to test the chromosome level to see if our baby has 46 chromosomes, which is normal or they are different.
They said if all the tests are normal, and if the fluid drains away by 18-20 weeks we may have a chance.
Its just so hard to understand how some fluid behind the neck could indicate these sort of problems.
I am only 24 years old, and so is my husband. We are young, fit and eat a very healthy diet, it just seems so un fair. Do you have any idea of our odds. What is the percentage of babies that do get over this? Have you had any sucess stories that could give us some hope? Thank you for your time and we hope to hear back soon. Laura
At Tue Jun 12, 08:24:00 AM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
Laura, I apologize for the delay in responding to your questions. I know this is hard, especially in a first pregnancy you have had so much trouble getting to. Unfortunately, finding the cystic hygroma in first trimester is associated with a very high risk for a baby that has a chromosomal abnormality, most often Down syndrome (trisomy 21 = 47,+21)), Turner syndrome (45XO,missing one sex chromosome), or trismoy 18 (47,+18), sometimes referred to as Edwards syndrome. Sometimes these are associated with gene defects and not chromosomal abnormalities per se. Examples of the latter include Noonan syndrome, Roberts syndrome, polysplenia syndrome, multiple pterygium syndrome, and others.
At times the baby has no chromosomal abnormality or obvious genetic condition. Under these circumstances, there is a high risk for a major heart abnormality as an underlying cause, although we do not know why babies develop cystic hygromas under these circumstances.
The prognosis for the baby depends on what problems the baby has, chromosomal, genetic, and/or associated structural. If the baby has no chromosomal abnormality and does not go into heart failure (develop hydrops fetalis), it may well survive the pregnancy. If no syndromic problems, chromosomal mosaicism, or gene defects are discovered after delivery, the baby may have a reasonable chance at doing well. Your doctors will discuss this more with you after they get your test results back. At that point (if they haven't already), they will probably refer you to a genetic counselor to get more information. Good luck to all of you and thank you for reading. By the way, it is hihly unlikely that anything you have any contol over caused this to happen. If you will, let me know what the tests show and how the pregnancy turns out...
At Sun Jun 24, 11:50:00 AM 2007,
Anonymous said…
Dr. Trofatter, I am 41 year old wtih a 14 week pregnacy. Due to AMA I elected to have Nuchal Translucency Scan done and the perinatologist found a large cystic hygroma, I was told extremely large 180mm3 and the doc was not optimistic. He performed CVS that day and we just recieved news that the FISH results were normal. Because there are no genetic defects, I was told we are looking at heart abnormalities, probably severe. My husband and I are deciding whether to terminate but the normal chromosome results makes this decision difficult. I have been doing research on the web for days now and I find myself unable to take care of myself and my family. I am reading the prognosis is poor and if I wait beyond 18 weeks I cannot terminate the pregnancy in my state. My question is can or should I get repeated ultrasound hoping the hygroma goes down and how often is and ultrasould indicated for this? Will the hygroma go down all at once or little by little or how much at a time? Please help me. Thank you
At Tue Jun 26, 02:47:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous June 24: Large cystic hygromas have a very poor prognosis, even if the baby is chromosomally normal. Even if th FISH results are reassuring at this point, your baby could have a chromosomal abnormality that was not detected by FISH. Your doctors have counseled you that this baby could also have a major cardiac malformation or other major abnormality that impedes return of fluid and lymph to the heart, even in the absence of a chromosomal abnormality. If the baby develops a condition called hydrpos fetalis, this would indicate heart failure for any reason and the prognosis is usually fatal at that point. If the baby is chromsomally normal, has no other genetic or syndromic problem, has no major heart abnormality, and resolves the cystic hygroma, it may well survive and do quite well in the long term. I would recommend another ultrasound before 18 weeks. In many cases, major heart and other abnormalities can be identified by that time and you will have the final results of the fetal chromosome studies back to guide your decision. I am so sorry. It is difficult to be in your situation. If you have not seen a specialist in Maternal-Fetal medicine, I suggest you consider that. Thank you for rading and best wishes to you and your family.
At Tue Aug 21, 01:55:00 PM 2007,
Anonymous said…
Doctor
On our 1st trimester baby scan we were told that baby had a 5mm NT. We hoped that the consultant could give us some better news on a scan a few days later, but we have the terrible news that it was not NT, but a large cystic hygroma of 7mm, extend down the back to the lumbar region. She gave us an 85% chance of choromsome problem and cardiac anomolies even if normal. Also of possible intrauterine death of fluid in the hygroma.
We are choosing to terminate, we can't wait in hope for CVS or Amnio MAY be postive but more likely negative. But we have terrible guilt in termination too, as baby seems ok at the moment.
But from what I read on the internet, there is a glimmer of hope that the babies do turn out normal. Is this just crazy hope or not?
Ed
At Wed Aug 22, 04:45:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Ed: Although the prognosis is poor, there is always a "glimmer of hope." With your ambivalence to pregnancy termination, why don't you have the CVS done. Most labs can give you an answer in as little as 72 hours if they do a "direct prep." If the baby ends up being chromosomally normal, or has a potentially viable condition such as Turner's syndrome, the "glimmer" may improve if the baby survives the first part of the pregnancy....and even if it is chromosomally normal and succumbs, you can walk away having giving it the "best shor" and it sounds like that is important for you. Just a thought. Good luck to both of you.
At Tue Mar 18, 05:17:00 AM 2008,
Cystic_Hygroma_Survivor said…
I am 36 living a "normal" life with Cystic Hygroma. I do not have a chromosomal abnromality nor do many of the other people on my support group who are also, living "normal" lives with Cystic Hygroma. What the doctor describes can be right but, is NOT the case for everyone. There is more information out that but, you must look hard. There is not enough research done on this rare condition, in my opinion. I have a support group, blog and friendship page on Myspace devoted to this topic. To help educate parents about ALL of their options and to share the other more positive side of this condition. There are other members on my page living "normal" lives. We have careers, have been married and have children. I personally, have 4 healthy children without Cystic Hygroma. There are other families on my group who have already faced what these parents here are facing. There are also, children, teens and adults on my group LIVING with Cystic Hygroma. I am so thankful my mom did not receive this information and was not asked to make a "decision" because I might not be here. I have used Cystic Hygroma in all of the above mentioned groups so, I should be pretty easy to find on Myspace.
At Wed Mar 19, 06:45:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To CH survivor. Thank you for your comment. I am sure there are many readers out there who will be comforted by your personal accounts. Thank you for reading! Dr T
At Wed Jul 02, 11:00:00 AM 2008,
Anonymous said…
Doctor,
I'm 40 years old, i had abortion last 2006 ( 6 weeks pregnacy),im not getting pregnant after that i took clomid last April 2008.Now i am about to miscarry again, im suppose to be 12 weeks AOG, but they only saw a fetal pole of 6 weeks in two consecutive ultrasound without heart beat.I want to know what seems to be the problem, why im always having miscarriage,i read about this chromosomal abnormality,how will I know who's carrying an abnormal chromosome between me and my husband?why it always happen at my 6 weeks f gestation?Do we have a chance to have a normal baby if for example one of us have an abnormal chromosome. Thank you for your response.
Alona
At Thu Jul 03, 06:29:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Alona: Most early miscarriages in a woman your age are the result of babies that have a chromosomal abnormality. Under most circumstances this is not something you or your husband carry (although it can be), it is the result of the chromosomes not dividing equally between your eggs during the final stages of producing these eggs. This event is called nondisjunction and it is the main cause of chromosomally abnormal babies (with Down syndrome and trisomy 18 for example) in women during the later stages of their reproductive life. Of course, you could have other erasons for your losses as well so I would suggest you see a specialist in reproductive endocrinology and infertility if you are not already doing so. You are running out of time and these specialists are in the best position to help find and treat a problem. Dr T
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