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. 

 

What is Loeys-Dietz Syndrome?

Something that I have faced, since being diagnosed with Loeys-Dietz Syndrome, is the feeling of isolation that comes with having a very rare disease. There are only 50 recorded cases of the type of Loeys-Dietz that I have. That’s a very small group when you consider the entire population. But then, the disease itself is fairly newly discovered so I am sure more will surface later. I feel bad hoping for that…

The feeling of isolation that goes with having such a rare disease is made worse by the fact that it is a very serious and life-threatening disease. You can go from being fine to being dead in a matter of minutes. It’s terrifying. Even more terrifying, however, is the fact that it’s rare to doctors as well. Most of my doctors have never met another patient with Loeys-Dietz. They don’t know how to treat it. They don’t know the complications of it. They don’t even have any literature on it and probably didn’t learn about it in Med School.

One thing that so many people take for granted is the fact that their doctors will know their diseases and know how to treat them.

For me, this is not the case and it could mean my life or my death.

So what is Loeys-Dietz Syndrome then?

Loeys-Dietz Syndrome is a vascular-type connective tissue disease. This means that the blood vessels are much weaker than normal peoples’ and are much more prone to aneurysms. With Loeys-Dietz Syndrome, it is almost a guarantee that you will develop an aneurysm at some point in your life.

For example, my grandfather has three aneurysms and my mother has two.

There are other disorders that also put you at greater risk for aneurysms: Marfans and Vascular Type Ehlers Danlos Syndrome. The catch, however, is that Loeys-Dietz can present with aneurysms in almost any artery, not just the aorta. Also, the aneurysms seen with Loeys-Dietz are much less stable than in Marfans or vEDS. This means that the aneurysms need to be monitored and treated much more aggressively, with surgery done on smaller aneurysms, than in similar vascular-type connective tissue diseases.

So what do you do? How do you not die?

Pretty much you just watch and wait. Maybe take a beta-blocker to keep your heart rate under control and your heart not too stressed. Or take  another drug that may or may not stop aneurysms (the clinical trials of that drug have not been as optimistic). You also do scans and echocardiograms to look for the aneurysms and hopefully stop them before they kill you.

Overall, the disease, in its big glorious picture form is pretty bleak. There’s a good chance that I will require surgeries. There’s a good chance that this will kill me. There’s a good chance that the people, family and friends, who have it will also be similarly affected.

Maybe I could deal with all that though and maybe I wouldn’t be so devastated if it wasn’t such a rare unknown disease and if it wasn’t such a fight to simply get the care that I need.