Any Arnold Chiari, Spina Biida? These are hard questions to ask

Any Arnold Chiari, Spina Bifida in this group? So hard to ask, but this runs in my extended family, along with spherocytosis, neural tube defects and pernicious anemia. Also, ADD, dyslexia, Ehlers Danlos, Loeys Dietz, Giantism, Dwarfism. I have genetic confirmation for all of this awful stuff.

When you say genetic confirmation, are you talking about your results from 23andme? Or real DNA testing?

My daughter and I both have sacral dimples which is supposed to be random in the general population but since we both have them, I’ve always wondered if it’s more of a genetic thing(like narrowly missed or mild spina bifida). My son has ehlers danlos but drs think he probably has the more common version of hypermobilty that lots of people have and don’t even realize it. My daughter and I can do a couple of the hypermobilty tricks but he can do a lot of them. ADD definitely runs in my family.

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Hi there, I have seen both your usernames pop up on the side discussions of a lot of genes I researched and have similar issues. EDS, tonsilar ectopia as seen in EDS but could also be seen as Chiari and a bunch of other things like spina bifida occulta in the form of a lumbosacral transitional thing with not entirely closed vertebral body that still needs to be looked into. My EDS is not typed yet but probably Classic. I ran a couple of gene templates, also for EDS and related issues and was stunned by all the yellows and reds. But when I looked at the actual rs numbers I did not find anything on them, so I started to turn things the other way around. The problem is that any gene has a LOT os SNP’s, many are very common variations and only a few cause problems. In Livewello, the list of diseases that comes up when you enter a SNP number on a certain gene is just everything that is ever found on any SNP in that gene. But the number of actual reported mutations or variations that actually cause the disease is extremely limited. And many of those are not genotyped by 23andme. And this is the same for the SNP’s that increase the likelihood of you getting something. It should say in research that this is found for the actual SNP that you carry. I found I do carry a bunch of exactly those SNPs for Ankylosing Spondelitis for example. Any other SNP on the relevant gene for a condition may be benign and meaningless. What I did next was find the actually pathological genes for many connective tissue problems on by opening the gene variations table. There are rs numbers with links there and you can paste them into a sandbox gene template. Or you can enter them in the raw data browser on 23andme and click the blue rs number link, which wil take you to the variation page. There, you can usually check what the minor allele is in case you don’t have a heterozygous genotype (in which case you can’t see in your raw data browser if your either homozygous or have two of the wild type and are off the hook) If it says 'With pathological allele" there, you can click the link to ClinVar right next to it and see the kind of variation to rule out you have that thing going. This can be important with an insertion/deletion or duplication. It’s very DIY, but is the only way to see if you actually have the reported variation, if it is genotyped that is :wink: I hope this helps!

I have genetic testing confirmation for Loeys Dietz from an MD who is board certified in Genetics, Pediatrics and GYN. It took 5 years to find the mutation. He initially thought I had ED4 and asked if he could genotype me, and I agreed, with the provision that I receive all results. I have MD genetic confirmation for Primary Immune Deficiency - Common Variable Immune Deficiency through a National Institute of Health study. I have a clinically MD issued diagnosis of Gorlin Goltz syndrome also confirmed by an NIH study out of St. Louis University Center for Human Genetics. I have an Ion Channelopathy with a potassium and magnesium malfunction, diagnosed by an MD and confirmed with an NIH study. I have entered a total of 14 NIH studies, and one private study. I am entering more, as we speak. All are genetic studies. My father had Spina Bifida Occulta, Alzheimers, and Lewy Body, MD and autopsy diagnosed. My sister’s daughter has Chiari and full blown spina bifida which are MD diagnosed. There were 2 fetal deaths with my mother, one with severe bone malformations. I was warned by my parents not to have children, which I heeded. I have been hunting for answers my whole life. I am a scientist as well. I donate to biobanks. All MD genetic testing matched 23andMe and Genos testing. All data was run through Promethease, Clinvar and Live Wello by me, and by the researchers, and all matched up. I am hunting for what ever answers I can find, anywhere I can find them. I am willing to share data and information with anyone who wants it. LiveWello is astounding, and when they started this GeneChat, I was so amazed. This is a real chance to contact and help each other. This is an opportunity for all of us, and I cannot thank LiveWello enough and the GeneChat developers enough. Also, keep an eye on the rH negaive factor.


I’ve found livewello and promethease to be quite useless since they only do the RS snps from 23andme, not the “i” snps. And a large majority of the RS snps are all junk. The only thing that’s been helpful about livewello is this new Genechat option. Enlis will decipher all of your data and has endless search options to break things down by pathogenic, deleterious(which is more important when dealing with unknown or unique variants) and a million other ways to look at your data. I will say though, out of the 1700 rare snps it spit out, MANY aren’t rare so you really need to double check everything.

Janet, did you have some kind of full genome sequencing(or similar) done? If so, have you checked it to see if the rare pathogenic porphyria gene showed up on it?

Oh and also, what’s the deal with the rh negative? Pretty sure I have that since I had to get the shots during pregnant. Isn’t rh negative somewhat common though?

I had full genome testing multiple times for NIH studies and through private research institutes. For $5.00, Promethease does a pretty amazing analysis using 23andme data, and it is easy to get the Clinvar pathogenic analysis. I think I have run about 3,000 templates on LiveWello. I also compared all physician tests with LiveWello and Promethease data, which matched the physician generated data. Genos does a more comprehensive data set than 23and me, and can be run through Promethease as well. I come up as homozygous for Porphyria. I am super sun sensitive, but have not had the purple urine. I am very fair, red blond hair, gray blue eyes, freckles. Super lanky, long arms, legs, fingers. Extremely hyperflexible. I have a promoter deletion for TGFBR-1 for the Loeys Dietz. I was glad to finally prove it, but it is kind of creepy. It was genotyped out of the Amish population. My maiden name is the Dutch name for Waffel Syrup. That was a tip.

The rH is complicated. I have gone to a LOT of meducal conventions as a patient and a speaker. I always ask the crowd how many are rH negative or half and half (like me). WAY more hands go up than what should be in a normal population. I ask people day to day if they are rH negative, and they ask me “How did you know?”. There is a look. Lanky, reddish, blond hair, fair skin, straightish hair. For the medical conferences, I noticed there were a LOT of fair haired pople, and to be honest, a lot of them looked just like me. I kind of look like Sissy Spacik. Often, the rH negatives are very pretty (and very sick). I call it the Guenivere effect. One of the doctors who tested me looked like me, and I asked if she was rH negative. She was, and had MTHFR mutations and Ehlers Danlos. She was freaked out that I diagnosed her before she diagnosed me.


Homozygous for which porphyria gene and which variant?

I will have to look it up. I am trying enlis right now!

If you have access to your raw data from the sequencing, I’d run that one through Enlis since it probably has significantly more data than 23

I live on the South Shore, south of Boston, near the Cape. We might consider making an affected group network (I guess a tiny one, but who cares!) Jeez, I couldn’t even spell Spina Bifida correctly!

Wow! My brother is rh neg, tall, blond etc, but got it from my dad, who’s short, dark but athletic… My mom is the tall slinky type, me too but in a slightly less tall version, very light build, blonde, fair skin. The reddish fair type runs on my moms side. We’re actually Dutch, maybe that helps. We think the EDS came from my dads side, but moms side has connective issue signs too, incl skin signs, the Marfanish build, Walker and Steinberg signs and sudden deaths.

Stroopwafels, yum :wink: I’m also curious about the porphyria genes if you can find them. Have had symptoms, many yellows and reds in the LW panel, but the really pathogenic SNP’s probably did not make it into that panel (or not genotyped) so I guess it doesn’t say much.

Janet, I’m originally from Massachusetts. Another sign we’re definitely related!(assuming that’s where you’re originally from)

Mari, I have severe sun sensitivity(to the point I can’t leave my house some days) as well as some of the systemic symptoms(like seizures, insane reactions to common medications, neuropathy, etc). I also react to fluorescent lighting worse than the sun sometimes. For 4 years now drs have suspected porphyria but my labs were borderline every time. Janet and I both have a very rare and pathogenic porphyria variant that showed up on 23andme. It didn’t make any sense since it was on hmbs(AIP which has nonsun sensitivity) and drs think I have ppox, cpox or fech. Mt Sinai genetics took an interest and decided to see if they could find that variant through sequencing. They couldn’t! Said 23andme made a mistake.

Mari, what did you mean when you said that you see our names pop up in the side discussions? Where?? Just curious because I assumed only the people who match the snp can see the discussion about it…

Yikes, that’s too bad that this results didn’t match up Ddddd! Are they testing again when you get acute symptoms? I remember seeing part of your conversation there about having the sun sensitivity although that kind of Porphyria was not associated with it, while many others that had it DID report the sun sensitivity. I think conversations come up for all SNP’s in the entire gene, but clicked through some that I have on the Porphyria genes panel and don’t see it now. I may have landed on it through a different panel or something? I went through my 23 raw data on the HMBS; all that’s genotyped there, which is not a lot, is clear in my case. Nothing on the Porfyria genes panel on Livewello is genotyped in my case though, so none of those show up at all. I have variations on all the genes in the panel, Alad is literally all yellow and red for me, plus there are 2 more ALAD variations in my raw data. I’ve had a couple of periods in my life where I was sun sensitive (red spots, blistering around joints and severe itching) and a couple that might have been attacks, with palpitations, insomnia, intestinal and back pain, confusion and once even seizures with it. But having EDS with cci there may have been other causes. I have neuropathy too.

Hmmm, Massachusetts! I called the Porphyria Dr., but I doubt he,will get back to me. He is in the Genetic department at Brigham. I have what are called benign variants, but this guy was pretty insistent that I had it. It looked to me like HE had it. I just couldn’t take getting another horrible diagnosis at the moment. Also, Obama Care pretty much destroyed my medical life. I used to have platinum insurance, and now I have tin insurance.

Are you hyper flexible, conective tissue-ish?

Ok but what about the hmbs one that we share? Or I’m assuming you responded because livewello flagged you as having it? And if it is indeed on your 23andme, does it show up on your real DNA sequencing?

Have you seen Dr. Jeff Milunski? Have you been to the EDS support group at Children’s Hospital in Waltham? There is one coming up on the 17th.

I also have been diagnosed, in 2007, with Joint Hypermobility, which I’ve been told is a very minor form of EDS. I got a CT scan a few years back for Endometriosis issues and cysts, and there was an incidental finding of spina bifida occulta at S1 vertebrae. The doctor didn’t even mention it to me! I found out only because I requested a copy of my scan results. That vertebrae is now slipping backwards… retrolithes(not exactly sure of the spelling). In addition, I have 4 bulging and herniated discs all the way from T12-S1. Essentially my entire lumbar region. I’ve been having almost constant bladder infections/minor Interstitial cystitis, and part of me is wondering if the newer bladder symptoms may be the result of the bulging discs combined with the endometriosis on my bladder and left ureter.

So, in 2007 I was seeing a rheumatologist. She also informed me that I have POTS as well as Sjögrens Syndrome, L-Carnitine deficiency, extremely elevated vitamin B6 and B12 (which I know now as a functional B12 deficiency) where the B12 was just pooling in my blood. Found out through genetic testing that I have some homozygous mutations in TCN, a transcobalamin transporter protein? I’d love to talk with anyone else that may also have this mutation. I haven’t been able to find out from anyone, docs included, what this mutation really means for me.

Anyways, In 2010 I was diagnosed with Hashimoto’s hypothyroidism, but I had suspected something was wrong with my thyroid for years but all my lab work kept coming back I’m range, until one day it wasn’t.

As far as the Chiari thing goes, I had an MRI done of my brain in 2009 and it looked like I had low lying cerebellar tonsils(?). A second MRI concluded that I do not have Chiari malformation. However, both MRIs were done with me lying flat on my back. I read somewhere that the best way to visualize and diagnose Chiari is to have an MRI done while standing upright, since that’s when most of my symptoms show up and honestly, it just makes sense! Part of me wants to request another MRI to be done while standing upright. Any thoughts???

Neural tube defect here. Xray found I had a spina bifida in low spine but it did not open to the skin. Imperfect vertebral formation left a gap in bone surrounding spinal cord.