Multiple Pterygium Syndrome - A Rare Cause of Recurrent Pregnancy Loss
Friday, September 28, 2007
Kenneth F. Trofatter, Jr., MD, PhD
Posted by to Fruit of the Womb at Tue Sep 18, 02:37:00 PM 2007
Hi,
My name is Nikky. I am 31 years old. I am currently 4 weeks pregnant for the 5th time. My first, third, and fourth pregnancies were ended due to the babies having multiple pterygium syndrome. It really surprised the doctors that this rare genetic syndrome has happened three times to me. The first baby was lost at 22 weeks, the third at 20 weeks, and the fourth at 19 weeks. I have a healthy 3 year old daughter (second pregnancy). Do you know if there are any ways to prevent this from happening in this pregnancy? Since we are the ones that educate the doctors about this, we are kind of stuck with just going for weekly ultrasounds until we notice the fetal abnormalities and lack of fetal movement. I am taking prenatal vitamins, 4 mg of folic acid, and vitamins B6 and B12. I also get a CVS (chorionic villus sampling) done at 11wks, but this cannot catch this abnormality. Do you think there are any tests to detect this? We were told that this syndrome can be found early second trimester or even in the third trimester. I just want to have a normal pregnancy. Thanks.
Hi Nikky. Thanks for writing and for sharing your story. Multiple pterygium syndromes (MPS) comprise a group of disorders characterized by multiple congenital anomalies typified by pterygia (webbing) of the neck, elbows, and knees and associated with limited fetal movement and joint contractures (fetal akinesia - arthrogryposis sequence), and many other abnormalities. MPS have been traditionally divided into lethal and nonlethal (Escobar) types. The lethal forms of the condition frequently exhibit facial clefting, intracranial abnormalities, large cystic hygromas, progressive fetal edema (hydrops) and death by midgestation and, as in your case, they have been found to be a rare cause of recurrent midtrimester pregnancy losses (Lockwood, et al., Am J Obstet Gynecol. 1988;159:474-6).
The inheritance of MPS appears to be variable, but the lethal form described by your history is most likely the result of either autosomal recessive inheritance or X-linked recessive inheritance. If the inheritance in your situation is autosomal recessive, that means that both you and your husband each carry one dose of the ‘bad gene’ (I am presuming neither one of you, nor your daughter, have characteristics of MPS) and 25% of your children (male and female) would be entirely normal genetically, 50% would be unaffected carriers, and 25% would develop the lethal condition and die prenatally.
If, on the other hand, the inheritance is X-linked recessive, then you must be the unaffected carrier (because your husband could not have the mutation or he would not be alive) and 50% of your daughters would be genetically normal, 50% would be carriers, 50% of your sons would be genetically normal, and 50% of your sons would die in utero. Sons who have the 'bad gene' on their X-chromosome cannot live and the genetically normal sons will not pass the ‘bad gene’ on to any of their children. Incidentally, if any of the children you lost were daughters, then you and your husband must have the autosomal recessive type of inheritance pattern detailed in the paragraph above.
So, to answer one of your questions, regardless of the inheritance, since this is a genetic problem, there is no way you can prevent it from happening. You just have to take your chances each time you get pregnant. But, the lethal forms of this condition can also often be detected earlier in pregnancy than 20 weeks in families known to carry the genetic mutation, thereby allowing them to make decisions about whether or not they continue to carry the pregnancy until the baby dies. The lethal condition is frequently associated with large septated cystic hygromas, or widened ‘nuchal translucencies’, frequently appearing to completely surround the body and in some cases the limbs, that may be visualized by ultrasound in late first trimester. Potentially, many of the other major physical abnormalities (such as diaphragmatic hernias, scoliosis, intracranial malformations, short forearms, and facial clefting), variably associated with the lethal syndrome, and hydrops fetalis may also be present well before 20 weeks.
You correctly point out that CVS cannot readily detect MPS because it is not a chromosomal abnormality per se, it is a genetic defect. Recent studies have shown that in a least some cases of MPS specific genetic defects have been identified as “germline-inactivating mutations in the embryonal acetylcholine receptor gamma subunit (CHRNG) in families with both lethal and nonlethal MPS” and have actually been mapped to the short arm of chromosome 2(2q36-37) (Morgan, et al., Am J Hum Genet. 2006;79:390-5). This finding does open up the possibility of earlier diagnosis by CVS and, possibly, even preimplantation genetic diagnosis, and with that is the potential for some form of interventive therapy.
In view of this information, Nikky, I suggest you review your history with a genetic counselor to find out if diagnosis of the condition can be established in your case on fetal tissues early in the pregnancy at some laboratory somewhere in the world - perhaps the one that did the study cited above! Again, thank you for reading and for sharing your situation with us. Best wishes for you and your family in the future.
Dr T
Labels: cystic hygroma, muliple pterygium syndrome, recurrent pregnancy loss
10 Comments:
At Wed Nov 28, 08:38:00 PM 2007,
Anonymous said…
Hi Nikki. I am so sorry for the loss of your previous pregnancies. Unfortunately, my husband and I have also suffered the loss of a son born with MPS six years ago. I have one daughter from a previous relationship, and one son that we concieved with the help of a sperm donor (this was the safest option for us). I try to stay up to date with the research done on MPS, but I am sure you are aware of the lack of information out there. From what I have gathered lately, they have not "found" the gene, therefore cannot specifically test for the syndrome. My husband and I opted to seek a sperm donor because I have one healthy daughter from a previous relationship, and he has no other biological children. My son lived for three months, but could not come home because of the his intense medical needs. I don't know where you are located, but I do know that staying in contact with a geneticist helps to keep you connected to the research being done on this rare syndrome. Best of luck to you and your husband...my name is also Nicky.
At Sun Dec 02, 08:07:00 AM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Nicky Nov 28: Thank you so much for sharing your story with us. It helps others who have and may go through what you have experienced to know that they are not alone. I wish more of our readers would provide us with this sort of feedback. It helps to share. Thanks for reading. Dr T
At Sat Jan 19, 04:22:00 PM 2008,
renee said…
Hi Nikki,
I too have had to terminate 3 pregnancies due to mps. Two were boys and the third was a girl. We do not have any children. We were told out best bet is a sperm donor, and we are going to start that process. It is so hard for both my husband and I because when you marry you never think these things will happen, and now I will have to pick out a donor for our baby. I hate that idea just because I want my husband's child, but i can not go thru the three months of waiting for mps to be diagnosed. We have spoken to geneticists and they all tell us there is a 25% chance that it will happen each time I get pregnant, unfortunately it had happened three times in a row and my mind and heart are at their breaking point.Emotionally i could not handle it if it happened again. I wish you all the best with your current pregnancy. I know haow hard this situation is. Best of luck
Renee
At Wed Jan 23, 06:14:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Renee: Jan 19: Thank you for your comment. Other readers will appreciate you willingness to share what you have been through. regards, Dr T.
At Sun Mar 23, 02:50:00 PM 2008,
Anonymous said…
They have found the gene where the mutation occurs to create the Multiple pterygium Syndrome. Or at least they have for our 2 children that are effected with the Escobar variant of the disease. According to the Molecular Neurosciences Group at Oxford, "The AChR gamma subunit gene (CHRNG) by PCR & DNA sequencing & detected a change in exon 5 of this gene. A single nucleotide insertion at position 392 in the gene (c392insA).
At Wed Mar 26, 07:13:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Mar 23: Thank you for the information! Other readers will appreciate it as well.
Dr T
At Sat Apr 12, 08:53:00 AM 2008,
Andrea said…
Hi, I just wanted to share my story. In 2004 at my 20 week scan I was told my baby had Lethal Multiple Pterygium syndrome. She was born on 30th May 2004 at 21+6 weeks. I was 19 years old & this was my 1st pregnancy. I fell pregnant again 6 weeks later & now have a healthy 3 year old girl. Post Mortem confirmed my baby girl had MPS & we had genetic councelling. I was also told we have a 25% chance of this reoccuring. There is no history of this in our families so we are unsure if we carry the gene or if this was a 1 in a million thing.
Thank you to everyone for sharing you experiences, it's nice to know I'm not the only one out there.
Andrea
At Tue Apr 15, 07:08:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Andrea: Thank YOU for sharing and best wishes for the future! Dr T
At Sun May 25, 12:42:00 PM 2008,
Stella said…
Hi, I also want to share my story. My daughter was born in December of 1992. We are from a small town in Southwest Kansas. Nobody knew what was wrong with her, other than she couldn't bend her knees and she had some webbing present. It wasn't until her 10th birthday that a genetecist at the Children's Hospital in Denver diagnosed her with MPS. She's 15 now and will be a freshman in High School. After reading your stories, I was shocked that we didn't know anything about her condition for 10 years. She's doing well. She has limited mobility, she can't run but gets around ok. Thank you for letting me share my story.
Stella
At Tue May 27, 06:08:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
Stella: Thank you for writing and sharing. It is hard to believe you had to wait 10 years for a diagnosis, but sometimes it's hard for folks to see the forest through the trees. Best wishes! Dr T
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