Midline birth defects and MTHFR mutations

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  • #2783 Reply


    In 2005, during a routine ultrasound at 20 weeks, my second child was diagnosed with alobar holoprosencephaly. It was not a typical presentation, but for lack of a better term… this was the diagnosis. Along with the brain malformation, there was a midline cleft lip and palate. Even though my daughter made it full-term, she died within 24 hours of birth. Despite the gamut of testing, including potential teratogenic infections, chromosomal abnormalities, etc… the doctors were never able to determine a cause. It was thought to be a one time isolated event, and unlikely to occur again.

    I had a healthy baby in 2006, and 2008. In 2011 and 2012, I lost two more babies who had bilateral cleft lip/palate, and malformation of the corpus callosum. I lost both babies around 20 weeks. Again, a multitude of testing was done and resulted in zero questions being answered.

    While the brain malformation of the first were more severe than the other two, doctors now suspect that my husband and I are carriers of a recessive holoprosencephaly gene that has yet to be discovered… thus, we have a 25% chance of recurrence… but this is just a guess.

    After my first loss, one geneticist mentioned the brain malformation resemled anencephaly, and even though I was taking prenatal, she suggested I boost up my folic acid in future pregnancies. After this most recent loss, it made me think that maybe she was onto something. I came across this website while researching MTHFR, and wanted to ask if this is something that could be related to my infant/fetal losses? Could an MTHFR mutation be the cause of the birth defects my children have suffered from?

    I should include that in my first pregnancy (which I had a healthy baby boy), I did suffer a partial placental abruption and possible miscarry of a twin at 13 weeks gestation. The abruption resolved itself, and there were no further complications. Furthermore, I have mitral valve prolapse, migraines with aura, bruise easily, as well as some peripheral neuropathies.

    As you can imagine, this time has been absolutely devastating. While I feel so blessed to have three healthy children, the loss of my other three has been difficult to handle. Any input would be grately appreciated.

    #2786 Reply


    Your losses must have been heartbreaking. Cleft lip and palate, placental abruption, miscarriage, mitral valve prolapse, bruising easily, peripheral neuropathies – these have low folate and/or cobalamin written all over them. Yes, MTHFR mutations could cause all these conditions. I don’t know anything about holoprosencephaly, but if it’s a midline birth defects, yes it could be related too.

    I would suggest that at the very minimum, that you and your husband get tested for MTHFR mutations. With the seriousness of the birth defects, I would further suggest that you and your husband think about going beyond just testing for MTHFR mutations and that you each have a methylation genome panel done – there’s about 30 methylation genes that Dr. Amy Yasko tests for, for example. Such a panel would include MTHFR as one of the genes tested for.

    Anyone that has MTHFR mutations will not benefit from folic acid. What is needed is the metabolically active form, L-5-methylfolate, as well as methylB12 and other cofactors. With a MTHFR mutation, folic acid just pools in the serum and actually inhibits the methylfolate form from binding to the receptors. Dr. Ben has articles and podcasts on this website that explain this in more depth.

    No matter if you wanted more children or not, I think genome testing could have important implications for you, your husband, and the children you have. Maybe there is an unknown gene, but maybe the genes we know about could explain everything. Maybe the fetus/children you lost had 3 or 4 MTHFR mutations, or a combination of methylation gene mutations. Maybe you are severely deficient in folate or methylB12 because of diet or a med that interferes with folate metabolism.

    #2908 Reply


    Thank you so much for replying. This was very helpful. I contacted my geneticist and she called my OB’s office to set up the blood draw. She wasn’t convinced of the correlation (I wasn’t too surprised… she seems to think more “in the box,”) but she went along with it since we, as she put it, “have grasped for thinner straws” in trying to find a diagnosis.

    I know I will be tested for fasting homocysteine, as well as MTHFR genome panel… but I’m not sure about the methylation panel. Do you know how I find out aqbout this? I read on this website that the MTHFR mutation testing is about $150… do you know about the cost of the methylation panel? Do you think my insurance will cover it?

    Also, you mentioned that perhaps the babies had the mutation… if that’s the case, if I got pregnant again and was on the proper form of folic acid, could that mean I can prevent the birth defects from happening? Does that mean that I am treating myself and the baby? Sorry… I am a little confused by this.

    Finally, if I come back negative for an MTHFR mutation, is it still worth having my husband tested?

    Thanks again for all of your help.

    #2909 Reply


    Your doctor may have tested your 2005 daughter for chromosomal abnormalities, but there’s probably just a certain panel of genes they look at. Is there any way to know if they tested the baby for MTHFR mutations?

    There are a few ways to do genome testing. If your doctor ordered a MTHFR panel, I hope it was with a lab that tests for both C677T and A1298C. Not all labs do the A1298c test. Another option for MTHFR testing is through this website. Dr. Ben charges $150 plus overnight shipping.

    If you want to do expanded genome testing, you can go two ways. A 23andMe genome test looks at over a half million genes. The 23andMe includes a test for A1298C and C677T plus a third MTHFR gene. There are over 50 known MTHFR genes, so only the most common MTHFR mutations are tested. It includes 25 methylation genes. You have to do a lot of the work interpreting it yourself, but there are blogs and websites that can help with that. It uses a spit sample and costs $299 plus overnight shipping. It also includes genetic geneology testing.

    Dr. Amy Yasko offers a methylation panel. She tests 30 methylation genes, 5 more than 23andMe, provides and interpretation, and has detailed and complex recommendations based on the test results. I think the cost is $495. Search on Amy Yasko and methylation panel. I think holistic heal is the website name. Not sure what kind of sample they use, but I suspect it’s blood.

    I know insurance won’t pay for Dr. Ben’s test or 23andME. Don’t know about Dr. Yasko’s test. A lot of insurance companies won’t pay for genome testing. You could ask your insurance company about their policy.

    Even if you are negative, it’s worth having your husband tested. If he does have a MTHFR mutation, it would impact his own health. Given that the 23andMe test includes the MTHFR test, and given the severity of the birth defects of some of your babies, if it was me, I’d be inclined to do the 23andMe test.

    If the birth defects were due to MTHFR mutations and consequent low folate and B12 levels, and if the fetus didn’t have 3 or 4 MTHFR mutations, I think you could prevent the birth defects, if you were replete nutritionally at the start of pregnancy and you took all the proper precautions for a MTHFR pregnancy. It’s very important to start the pregnancy totally sufficient in all nutrients, because neural tube defects occur at around 4 weeks of pregnancy. Taking proper supplementation of active forms of folate and B12 and supporting cofactors during pregnancy will be a treatment for you and your baby. You are the source of your baby’s nutrition, and if you’re replete, then there’s a better chance the baby can get what it needs.

    #460432 Reply


    Hi there, thank you for all this info. FinonaB so sorry for your losses. :( Lynn_M…you speak of “Taking proper supplementation of active forms of folate and B12 and supporting cofactors during pregnancy will be a treatment for you and your baby. You are the source of your baby’s nutrition, and if you’re replete, then there’s a better chance the baby can get what it needs.”…what are these proper active forms of supplementation please? My 5th baby (son) was born with upper lip tie, posterior tongue tie, third nipple, and also branchial cleft cyst (although, not a cyst yet, he has the dimple at the base of his collar bone which I guess is type IV and more rare than the I, II, or III?)..anyway…he was the first pregnancy I nursed a previous baby with (until 20 weeks gestation), and I also got an early ultrasound at 5 weeks for bleeding (which I thought could have caused the branchial cleft defect). I am researching and wondering if he may have a mthfr gene mutation. If we get pregnant again I am considering nursing as long as possible again but want to make sure my body has what it needs to provide for another baby but also to make quality milk etc. Any insight? Thanks so much!

    #482295 Reply


    Midline defects and MTHFR, good little video


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