Ehlers-Danlos Syndrome (EDS) is an inherited group of disorders of connective tissue. There are several different types of EDS but the vascular type (vEDS), also know at Type IV EDS, is the most severe (Barabas, 1967). Although there are a variety of types of connective tissue, EDS primarily affects Type III collagen, which is required for normal development and function of bones, tendons, and skin (Beighton, 1998).
EDS Mutation
Patients with vEDS have a mutation in COL3A1, the gene involved in the synthesis of collagen, which causes decreased or absent synthesis of collagen (Smith et al, 1997). This is highly problematic because collagen is located in blood vessels, where it is used to increase strength and flexibility; the effects on blood vessels make EDS particularly deadly, but thankfully EDS is not particularly common. Surprisingly, the entire disease is actually caused by a single mutation in Collagen Type III, which changes the structure of the protein and makes it dysfunctional (Mao and Bristow, 2011). The mutation almost always occurs in a particular region of the protein that is used to bind to other collagen proteins. Three collagen proteins always bind together into a trimer, which is required for collagen functionality; when not bound in a trimer, collagen is useless, as it cannot provide functional or structural support (Mizuno et al, 2013).
Vascular type EDS includes symptoms that are not seen in other types of EDS. In this type of EDS, collagen is particularly weak, making blood vessels particularly fragile. The breakage of vessels obviously causes bleeding, which can be deadly if it occurs in a large artery, like the aorta, or in the brain. Other organs, including the uterus and intestine, also rely on collagen for structural support, and these organs are also more likely to rupture due to decreased structural integrity; this is particularly problematic during childbirth, where the uterus is particularly vulnerable. Other characteristic symptoms of vEDS include sunken eyes, and pinched lips and nose, which are all caused by the lack of structural support that is used to maintain the normal features of the face. Doctors frequently use these symptoms to diagnose potential vEDS patients, and biochemical analysis can be used to show the presence of decreased or mutated collagen (Germain and Herrera, 2004).
Unfortunately, no good treatment option is currently available for the disease, and many patients die due to blood vessel breakage at the average age of 51 (Pepin, 2000). In general, vEDS treatment is limited to treating side effects, and plastic surgery can be used to correct some of the changes in facial structure. While emergency surgery can be used with minimal success to repair broken blood vessels, it is highly preferable to preemptively screen for areas of blood vessels that are damaged or weak, as these are more susceptible to breakage (Pope, 1975). These weaknesses can then be repaired before the vessel breaks by inserting a stent, which will help strengthen the blood vessel and prevent breakage. Thus, the most severe complications of the disease can be delayed or avoided, increasing the average lifespan. It is generally not possible to prevent organ rupture, and this can also require surgery with major side effects. Excitingly, a recent clinical trial showed that Celiprolol, a medication already used to treat high blood pressure, could help decrease the likelihood of blood vessel rupture in patients with vEDS (Milewicz, 2014). While this trial was somewhat small, it is the first hope of preventative treatment for the disease.
More Information:
Molecular Basis of the Disease State
Treatment and Disease Management
I know of someone who had EDS, so this straightforward article was very helpful in understanding more about his disease. Good information for a lay person. (Side note, I noticed two typos. In the first paragraph, “also know at Type IV EDS” should be known as, and in the first paragraph under the EDS Mutation heading, last sentence, “always bind together in a timer” should be trimer.)
Thanks for your comments, you were right, it’s definitely a trimer!
I think that as a whole, this overview was very informative and understandable to someone who is not a scientist. My main suggestion would be to further clarify the section describing the mutation because it seems that it is a more complicated scientific process. I was unsure of what a trimer was, and think that it might require a link to a definition.
Thanks for letting me know. I’ll add a definition for a trimer, which is simply three proteins that are bound together, to the article. I’ll try to clarify a little more about the mutation, but I just didn’t want that section to have so much information in it that it was overwhelming. It really is a relatively simple process though, as the mutation affects the part of collagen that binds to other collagen proteins. The mutation changes the structure of the collagen in a way that prevents this binding, which makes the collagen weak, and thus subject to breakage
I am very confused because you said that this disease is from type IV collagen mess up but then in the second paragraph you said it’s from type III? You made a mistake or need to explain the difference between those two statements.
Thanks for catching that, it is definitely type III!
This article was mostly easy to understand from the perspective of a non-scientist. However, I don’t understand what the term “mutation” means in this context.
Thanks for letting me know that. In this context, a mutation is simply a change in the DNA. DNA is composed of individual units (called nucleotides) that are arranged in a very specific order. There are only four different kinds of nucleotides, and they are not interchangeable, as a change from one nucleotide to another can be disasterous. In Ehlers Danlos syndrome, a mutation occurs where one nucleotide is simply substituted for a different nucleotide; this is problematic because this new nucleotide prevents the protein from binding to other collagen units, which is required for normal collagen function.