The following comment and query was recently left on my post "Grand Rounds 3.52 - Thanks Kerri!" Although it had nothing to do with the subject of my Grand Rounds offering, it is still a fascinating condition most worthy of a post all its own – multiple pterygium syndrome...
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