Your Handy-Dandy Guide to Connective Tissue Disorders

There are many different types of Connective Tissue Disorders (CTDs) with symptoms that are all very similar. One thing that holds true among all the CTDs, however, is that they are genetic/heritable (at least the ones I am discussing here). The two most common type in which genetic diseases are inherited are: autosomal dominant and autosomal recessive.

To understand what these mean, you have to first understand the genetics behind the disease. Most everything in our body is a product of our “genes”. A gene is a section of DNA that contains the blueprint for specific proteins. Everyone has two copies of a gene: One from their mother and one from their father. When a person inherits a genetic disorder, it means that either one or both copies of a specific gene is “damaged” ie. mutated.

With autosomal recessive disorders (like some rare types of Ehlers Danlos syndrome) you need both genes to be mutated in order to have the disorder, ie. you need to inherit a bad copy from both your mother and your father. If you only have one mutated gene, then you are a “carrier” without symptoms of the disorder. You can only have an autosomal recessive disorder if you have two mutations and you cannot pass the disorder to your children (although they would have 50% chance of being a carrier).

With autosomal dominant disorders (like most types of CTDs including the more common types of EDS, Marfan, Loeys-Dietz Syndrome…etc) you only need to have one gene mutated in order to have the disorder, ie. you can inherit a bad disorder-causing gene from either your father or your mother. This means that your mother or father would also have the disorder and that you have 50% chance of passing on the disorder.

Very rarely, someone can present with a new mutation and will not have a family history of the mutation. This occurs more frequently in some connective tissue disorders compared to others.

Here is a list of the more common CTDs and their associated genes (click on the disorder to be redirected to a more detailed explanation of the disorder and its symptoms):

Ehlers-Danlos Syndrome, Hypermobility Type – No known genes (Autosomal Dominant)

Ehlers-Danlos Syndrome, Classic Type – Col5a1 & Col5a2 (Autosomal Dominant)

Ehlers-Danlos Syndrome, Vascular Type – Col3a1 (Autosomal Dominant)

Ehlers-Danlos Syndrome, Kyphoscoliotic Type – PLOD1 (Autosomal Recessive)

Marfan Syndrome – FBN1 (Autosomal Dominant)

Loeys-Dietz Syndrome (Types 1-5) – TGFBR1, TGFBR2, SMAD3, TGFB2 & TGFB3 (Autosomal Dominant)

Shprintzen-Goldberg syndrome – SKI (Autosomal Dominant)

Homocystinuria – CBS (Autosomal Recessive)

Stickler Syndrome – Col2a1, Col11a1, Col11a2, Col9a1, Col9a2, & Col9a3 (Autosomal Dominant or Autosomal Recessive – depending on the affected gene)

*This post is written by a PhD Student with a background in genetics.

**This post does not contain all methods of inheritance and is an abridged list of connective tissue disorders. 

 

Genetics Results Part 1: Goodbye Ehlers-Danlos Syndrome

Since my last blog-post I have been unsure about how to write the next couple of blogs. I eventually decided to do a two-part-results reveal. This is partially because I believe that saying “goodbye” to EDS should be a post in and of itself. But I am also not quite ready to share the results of my genetic testing for several reasons (one being that I would like to remain anonymous still and right now I’m sure that my family is currently googling the abnormal gene and the condition it’s associated with). I will share one thing though; I do not have Ehlers Danlos Syndrome.

I started this blog as a method of detailing my journey with EDS and also to raise awareness. While this blog is only a little over a year long, I have known about and suspected EDS as my diagnosis for over 5 years. I have researched it, I have joined support groups for it, and I have advocated for it. Ehlers-Danlos Syndrome has always played such an integral character in the story behind my health.

For many years I just assumed that EDS was my answer and didn’t bother looking any farther or getting a formal diagnosis. There is no treatment, there is no cure, and I just didn’t see the point in going through the hoops. After a while though, as I started to get worse and to become more and more sick I began to realize how beneficial a diagnosis could be. Once I started developing the co-morbid illnesses that go along with EDS (such as POTS, Gastroparesis, MCAD,…etc.), I realized the importance of having a diagnosis… It makes doctors take you seriously. With a diagnosis of EDS doctors know what co-morbid diagnoses to consider. With an EDS diagnosis maybe I would have had a Tilt Table Test to check for my POTS right at the start of my search, instead of after countless other tests. Above all else though, a diagnosis would give me credence. I wouldn’t be the hysterical female who is clearly a hypochondriac. I would be the young patient with a genetic disease.

So I started down the road towards getting a diagnosis of EDS. After the first appointment with my geneticist, when I was told that I wasn’t going to walk out of that appointment with a diagnosis of Hypermobile Type EDS, I realized that the diagnostic process was going to take longer than I thought. Next I was confronted with the idea that instead of Hypermobile Type, I might actually be diagnosed with Classic Type or possibly even the scarier Vascular Type. Always though, there was the underlying belief that I would eventually be diagnosed with EDS. Sure my geneticist listed several other conditions as a differential diagnosis, but EDS was always the assumption.

The majority of my blog posts had tags of “Ehlers-Danlos Syndrome”, “EDS”, “EDS woes”,…etc.

But it’s not EDS.

I do not have Ehlers-Danlos Syndrome.

So this is my “Goodbye”. I have decided to keep the earlier blog posts the same. I will not remove or change the tags. Nor will I delete the ones where I have talked about having EDS. But from here forward I will start to talk about my new diagnosis. If any of my readers have a question concerning EDS, however, or just need someone to talk to who understands the disease and the process of coming to a diagnosis, please pleases feel free to comment and/or ask me anything.

Goodbye Ehlers-Danlos Syndrome.

Genetic Testing: Part 2

The genetic results are in and…

I have no idea what to make of it. At least not yet.

I received an email on Monday night telling me that my online health record had been updated. My immediate response was intense panic. What if the test hadn’t shown anything? What if it had? I signed on and looked at the results and they said….

Results pic

….Nothing. They didn’t actually post my results.

Now, this all happened while I was traveling back home from visiting family. So I got these results late at night in my hotel room and the next day I was going to catch a bus at the airport to take me back home.

So while waiting for the bus at the airport the next day, I called the pathology lab to get a copy of my original report. The woman did not want to give me my results and could not be swayed despite the fact that my online record said to specifically call the lab to get a copy of the original report. She said I had to contact my genetic counselor.

I finally got my genetic counselor on the line an hour or two later while I was on the bus. The genetic counselor didn’t want to give me my results either (Hint.. by now I know that if they don’t want to give you the results it means that there’s probably something they’re not ready to tell you yet). She did admit that it showed something though and I did finally manage to coerce her into telling me which gene was affected. She also told me that she had planned on specifically bringing up my case in a meeting the next day and that my geneticist would let me know what all is going on next week.

I’m so close to finally having an answer…

Genetic Testing

My insurance approved the genetic testing!!! I was really scared about this. There are several things that had me worried. The first one being that I lose insurance at the end of May. I know that insurance companies move slowly and I was really beginning to doubt whether there would be enough time for me to get the testing approved. I could never afford the testing without insurance covering most of it. The second thing that concerned me is my moving in July. I’m moving halfway across the country (USA) to a completely different area. I am going to have to start completely over with finding new doctors and not many geneticists support genetic testing to begin with. So I was very afraid that if I moved before I could get this test done, I would never be able to get it done.

But now I don’t have to worry!! I’m so excited!! Look at all the diseases that this test tests for:

genes 2

Unfortunately I won’t get my results for another 3-4 months.

Also unfortunate is the fact that I will probably start to go insane towards the end of that time period. I don’t know what I will do if the test doesn’t show anything.

New Cardiology Appointment

For around two years now I’ve had the same cardiologist. Maybe in the beginning she was a good doctor. That was when she thought I was dying and she acted pretty quickly to get the proper tests. Once the cardiac cath. showed that I was not dying, however, she suddenly seemed to have lost interest in trying to help me. I guess I lost all patient-appeal when I was no longer a patient with a terminal illness. So anytime I went to her with a problem, she would just increase the dosage of my meds. After one particularly horribly disappointing appointment, I found myself crying in a stairwell. In that stairwell I finally decided that I was never going back.

So I found a new cardiologist, with whom I had my first appointment today.

The appointment started off with a nurse getting some background information. I usually hate this part because it’s awkward. “Do you have a history or urinary tract infections?”…”Er, no… but I’ve had blood in my urine… it wasn’t an infection. I didn’t have kidney stones either…yeah…” It’s hard to give a medical history when things don’t fit a normal picture. So once we got past that awkwardness (and really, it’s not hard for me to make something awkward), she took my bp, pulse, and an EKG and then left me in the room to wait for the doctor.

Who appeared within a minute (That happens?! I was totally expecting to live and die in that room before he came in…). I however, became instantly wary when he asked why I needed a cardiologist. He asked what a 25 y/o was doing there. He asked who referred me. I was terrified that I had found yet another doctor who seemed to already be convinced that I was fine before even examining me.

Turns out it was just his method of trying to get to the reason I was there… Once he started looking through the records he had (most of them from the geneticist) his first comment was “you’re a complex case” While that’s not what everyone wants to hear, it is much better than him calling me a hypochondriac. So I was a bit relieved to hear it.

Then we went through the “Oh my geneticist feels strongly that I have either Classic or Vascular EDS and is testing me” bit. He asked me if I was flexible. I performed some circus tricks. He cringed. He then tried to tell me how horrible vascular type can be and I reassured him that I have a strong family history of aneurysms and therefore already know.

It’s freaky to hear your doctor say “Poor…” over and over while reading your report.

His commentary was pretty funny though: “You had a DEXA scan?!?…oh.. it showed something…” He needs to realize I’m a young person with old diseases or he’s going to be in for some unpleasant surprises. I can’t wait till he reads my GI scopes reports (although I’m not sure why a cardio would be reading those…).

So I finally have a cardio who seems to be able to handle “complex cases” without getting scared and without throwing drugs at me hoping they’ll do something. In fact, he doesn’t even like that I’m on the beta blockers at such a young age. Unfortunately all that means that I need to have a stress test. I’m definitely afraid of this test. I know it’s going to be unpleasant at the very least. Oh well. I’m still hoping for some answers and maybe a bad stress test will give me a chance at a solution/cure. Silver lining?

Am I My Illness??

Does my illness define me?

This question has haunted me for a while now. I call it a “mirror question”. A question that I’m afraid to truly ask for fear of what I’ll find out about myself.

For a while, I had thought that perhaps I was my illness. Maybe it was something that I had let define me. But worst of all, I was afraid it was something about me that I  liked. I would stay up at night thinking “what would I do if I didn’t have these symptoms?” and to my horror, I felt upset at the idea. So did this mean that I had let my illness define me?

No.

My illness does not define me.

It took me a little bit of time to realize that, but first I had to be brave and finally face my “mirror question”. When I finally thought about it however, I realized that the lack of knowledge about what was affecting me was the thing that was making me upset. This is a bit tricky and a tad convoluted, but I hadn’t quite realized that if I didn’t have my symptoms, then I wouldn’t be sick. All I had considered was that I would have to start all over in trying to figure out what was wrong.

Once I realized that this was my hang up, I was able to answer my question honestly: If I didn’t have these symptoms I would do everything that I already am doing, but it would be a lot more easily done.

So what am I?

I am a Masters student in biology. I will soon be a PhD student in cellular biology (I got accepted into three programs!!!). I work full-time hours. I have many hobbies that I enjoy. I have friends who I hang out with.

So what does my illness add to this equation?

It makes everything so much harder. Those full-time hours? Being a graduate student? Those are so very hard to juggle by themselves, but with an illness? It’s a challenge. And that’s me being modest about how much of a challenge it actually presents. Often, I feel like a failure, because I can’t do it as easily as most people seem to be able to. I have limits. My illness gives me limits.

I would give anything to be able to get rid of those limits.

ER Update

I rarely go to the ER. In recent memory, I have only gone twice before. The first time I thought I was dying (Spoiler alert: I didn’t). The second time I wanted to make sure my kidneys were ok (This trip earned me my first nephrology appointment). But the point here is that I rarely rarely go. Normally I go to an Urgent Care clinic or I make a doctor appointment. I just don’t do ERs. And I especially don’t go for something like pain… I can put up with that at home right? Wrong. So very wrong!

To be fair… I attempted to go to the Urgent Care clinic first.

To be honest… I really didn’t put up a fight when they suggested the ER.

My day started off alright. I woke up with no pain. Walked over to the mirror in no pain. Then I stretched. PAIN!! All of a sudden something cracked in my neck, my muscles all went into spasm, and I could no longer move my head without excruciating pain. I also had a wave of panic that I had seriously screwed up my spine. I was terrified that one wrong move would result in something worse than pain. I get a little paranoid when it comes to my spine.

So I took a shower, hoping that the warm water would relax it. When that didn’t work, I called my mom (yes, I still call my mommy when I’m sick) telling her what happened and that I was going to go to Urgent Care. Once there, I sat in the waiting room for 2 very painful hours. When I was finally taken back, they performed an xray which showed that the vertebrae were fine. Then the lovely doctor came in, told me everything was good, that I could go home, and that I should take Tylenol for the pain. That was the point where I burst into tears. Sobbing that Tylenol did nothing and that my stomach couldn’t take any more NSAIDs (Throwing up blood? Yeah, not fun.). I think that was also the point where the doctor finally realized how much pain I was truly in. He suggested I go to the ER to get a CT scan and get it looked at better. So that’s what I did. The end result was that there was no new damage to my spine, but my muscles were being completely pissy. Thankfully they sent me home with a muscle relaxer and some vicodin.

It took about a week for the meds to relax the muscles. That was pretty much the week from h*ll.

In other news… I got a new toy!

Dammit doll 1Dammit doll 2

 

 

 

 

 

 

 

 

 

I’m sure this will come in handy in the future!

The 2nd Genetics Appointment: Part B

So a little time has passed and I’ve digested more of what was said and tested for during the second genetics appointment. Also, most importantly, I got my appointment summary. My geneticist likes to keep her opinions to herself. At my first appointment I was told that it is much easier to diagnose something than to take back a diagnosis. This makes sense, but it’s still very hard for me to go so long having no idea what she’s thinking and what diagnoses she’s considering. Luckily, she writes appointment summaries and sends them to my PCP. I get them from him and can then get a better idea of what’s going on.

One thing about this latest report that amazed me is how much she knew about my previous health history. She must have read everything I’d given her last time.  Seriously, she actually wrote out the numbers of all my abnormal CPK tests (probably because I’ve only had like 4 or 5 of them haha). Reading the medical history section is intimidating. Seeing all your health problems written out in paragraph form and realizing that there’s a lot going on is not the most comfriting. “She was found to have tricuspid regurgitation”…”She was diagnosed with spina bifida occulta”…”She underwent an EEG and that was reportedly showing some slowing in temporal lobe”…”She was noted to have extra ribs”…”she was diagnosed with osteopenia”…On and on and on. I swear I’m not high maintenance.

After the medical history part, comes the physical examination write up. One thing you never want to see in a genetics report….

genetics compliment

…is a compliment and I sure got a lot of them. Which brings us to the next and most important portion of my report: the clinical impression portion. She still seems to think that Vascular EDS  (“Given the patient’s skin, joint and hyperelasticity of the skin and excessive bleeding…”) is a possibility but that I also have the presentation of the Classical type. So it seems like I’m definitely getting tested for V-EDS. Lovely. So the prevailing thoughts on a connective tissue disease are that I have V-EDS or C-EDS. She, however, also lists that I have overlap features of Marfan syndrome, Loey-Dietz syndrome, along with other connective tissue disorders. Apparently the osteopenia adds collagen 1 defects, tenascin XB, and Sticker syndrome to the mix.

She still maintains that I have a comorbid disease along with the probable EDS. Unfortunately the comorbid disease is making things rather confusing (“Comorbid entities and a blend of phenotype is a concern in this patient.”) A chromosomal abnormality seems possible. I’m not sure about that myself. I just don’t seem to fit the phenotype for that one, although she does state that it can be variable in phenotype. She seems to be more insistent on the possibility of a mitochondrial disease or an inborn error of the metabolism (IEM) disease. In fact, she even mentioned IEM as a possibility in the primary diagnoses section.

Over all, I guess we’re narrowing the possibilities down a bit more, but I really am impatient (I don’t put the “patient” in patience). I just want to know what I’m dealing with and move on with my life. Giving something a name really makes a huge difference in being able to start accepting it.

The 2nd Genetics Appointment

I finally had my genetics follow-up and am not sure how I feel about it. At my last appointment, so many different possibilities were listed as potential diagnoses. I was confronted with the possibility that not only do I have a connective tissue disease (EDS), but I may also have something else as a comorbid condition.  The doctor listed so many possibilities: Inborn Errors of the Metabolism, Mitochondrial Disease, Alport Syndrome, liver disease/cancer, thyroid disease, Polycystic Kidney Disease…etc. Essentially, instead of getting answers, I got more questions (and an intense urge to consult Dr. Google). My second genetics appointment was very much the same.

I thought that I would start to get things narrowed down at my second genetics appointment. That’s what the first round of testing was right? To be able to rule out some things, pin-point other things? Turns out I was partially right. What I didn’t account for was that for everything that was ruled out, a new diagnosis was considered. I don’t have Polycystic Kidney Disease, but now we’re testing for porphyria. My Alpha-Fetaprotein test was normal, so we’re testing Carbohydrate Deficient Transferrin (I don’t drink).  The three tests that were abnormal didn’t even yield me any answers. They were just repeated.

So what did I learn? As previously stated, I don’t have Polycystic Kidney Disease. I also don’t have Alport Syndrome or thyroid disease (seriously.. I feel like I’m the ONLY person who doesn’t have thyroid disease). I probably don’t have a fatty acid oxidation disorder. I’m fairly certain I don’t have liver cancer (I still have no idea what made her run that test).

So what is she testing me for now? She re-ran the three abnormal tests: urine organic acids, very long chain fatty acids, and acetylcarnitine profile, along with a bunch of other tests (eight tubes of blood and two urine samples). I think ultimately the mystery disease will either end up being some rare metabolic disorder or a mitochondrial disease. She’s testing me specifically for MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy) because of my GI symptoms, but I really don’t think I have that type. I’m not sure about my having porhyria either. Some things fit and some don’t. I think whatever I do end up having though is going to be an unusual presentation.

One perk about having my appointment at Children's is that the blood draw rooms are awesome.

One perk about having my appointment at Children’s is that the blood draw rooms are awesome.

I loved the frog room :D

I loved the frog room 😀

Along with the testing, the geneticist performed another exam. Yay for more pictures! This time she only took a picture of my hand, elbows, and knees. This makes twice she’s taken these same pictures. She also went over my flexibility again, along with reflexes and eye movements. Apparently I have slightly “brisk” reflexes, tremors, and a nystagmus. Who would have thought? Not sure what all that means though and honestly it could mean nothing.  Hopefully I’ll get at least a couple of answers when I read the appointment summary letter. Till then, I’m taking this whole experience as a crash course in patience.

Update: Nephrology Appointment

Today was my 2nd nephrology appointment and overall it went pretty well. At least, as well as someone with a rarer illness can expect it to go. For one thing: My doctor actually did RESEARCH! I was stunned!! Aside from my geneticist, he’s the only one who said something about EDS that I didn’t already know!! Something relevant to my current symptoms! It was amazing! And for another thing: He consulted another specialist instead of just giving me a referral! Yes!! This means a LOT. I’m tired of having an ever-increasing list of specialists whom I go to. It’s exhausting and slightly depressing. These two things alone made the appointment amazing and they have nothing to do with my actual health. This goes to show how important doctor behavior is though. 

As for what came of the appointment, things are a little… frustrating… As is normally the case, the very first thing you do when seeing a doctor is to get weighed. This was one of the things I was most anxious about. Unfortunately, I’ve lost more weight and I’m down to 118lbs now. This isn’t a drastic change and it’s not like I’ve lost a huge amount of weight suddenly, but it’s not normal for me. It’s a new symptom. It’s concerning. It’s consistent. And it’s annoying as h*ll that I can’t get any doctor to take it seriously! It’s like they’re waiting till I finally crash before addressing it. Frankly, I’d like to avoid the crash that will happen if this continues. But oh well. Either way, it’s not a kidney doc’s place to worry about my weight anyway.

Since all my kidney tests came back relatively normal, the next logical step would be seeing a urologist and performing a cystoscopy to see if there’s anything going on in my bladder that could be causing the bloody urine. However my nephrologist consulted with the urologist (aren’t I smart for knowing all these different doctor specialties??) and they decided that, because of my EDS, it was too much of a risk at the moment to do a cystoscopy. With EDS, tissues can be fragile and “friable”. This means that I’m prone to being easily damaged and to easy bleeding. I wasn’t really surprised to hear this, especially since my GI scopes showed friable tissue. Why should my bladder be any different? Personally, I’m happy to bypass the whole shoving a scope up my pee-hole thing anyway. Not my idea of fun. So I was given two possible explanations: 1) I have bladder diverticulum (which is associated with Classical EDS…something I didn’t know) which can bleed, explaining the bloody urine. Or 2) I could have a renal aneurysm (which would be more possible with Vascular EDS). These rarely bleed, but it’s still a possibility. Since I’m getting tested for both of those types of EDS, I guess they’re both likely. The nephrologist believes I have the Vascular type, but I’m not so sure. I do have a family history of aneurysms though so I can’t really rule out a renal one. 

In the end, we decided to do a “watch and wait” approach. I’m completely fine with this though since I was getting tired of running through all the medical hoops. I need a break. I’m not sure I would have been willing to undergo a cystoscopy at the moment anyway. There’s something so very demoralizing about undergoing a procedure with the whole IV thing and sedation and hospital beds.. even if it is outpatient. So I get a free-pass for 6 months at which point I will do repeat blood work of the tests which I had abnormal results on. But for now…. Freedom!! Life is good 😀