Ehlers Danlos Syndrome

Hunter Beach
Biology 1010
Salt lake community college
 Ehlers Danlos syndrome(EDS) is named for two dermatologists Edvard Ehlers and
Henri-Alexandre Danlos who were the first to describe this connective tissue disorder in detail in
the early 1900s. Though descriptions of individuals with similar symptoms have been described
going back hundreds of years (Parapia & Jackson, 2008).
EDS is a genetic disorder that has different inheritance patterns based on the specific
subtype. Some subtypes follow autosomal dominant patterns, while others follow autosomal
recessive patterns(Beighton, 1970). What this means is that it can lie dormant in a family for
generations reappearing suddenly, this can make diagnosis difficult. With the autosomal
dominant inheritance pattern, you can end up having the gene expressed in multiple siblings.
What EDS boils down to is a bad recipe for collagen. Essentially as the cells assemble
collagen proteins for the construction of things like skin, bones, organs, ligaments, and blood
vessels, they construct the collagen improperly (Barabas,1967). This makes it so that it doesn’t
fold correctly, which in turn makes it so that the collagen doesn’t fit together properly (Reinstein
et al., 2012). The end result being that any tissue using the type of collagen that is built
incorrectly isn’t structurally sound.
The signs, symptoms, and prognosis of EDS are wide ranging depending on the specific
subtype that the individual has. Generally, the signs include things like lax joints, soft skin,
unusual scaring, and easy bruising(Parapia & Jackson, 2008). What this means is that people
with EDS are prone to dislocations and partial dislocations of joints. When someone with EDS
gets injured it takes far longer to heal and any scars they have tend to be distinct, in that the skin
is thin and papery.
The difficult part is that the subtypes share symptoms but some carry an extremely high
risk of complications that are unusual in the other subtypes. An example of this would be with
Vascular Ehlers Danlos Syndrome(vEDS), which has the same general symptoms of EDS, but
far more lethal. Those with vEDS have a high mortality rate due to invisible differences. The
complications that set vEDS apart are serious in that they are not obvious until they become
sudden life-threatening problems such as bissected aorta, perforated gut, ruptured arteries, and
death(Barabas,1967; Beighton, 1970; Castori, 2012). In the case of vEDS the exact gene that
causes it is COL3A1 which handles the assembly of collagen III proteins (Castori, 2012). Post
mortem rediagnosis to vEDS is not an unheard of practice(Barabas,1967). After someone has a
received a diagnosis of any EDS they are typically referred for genetic testing to verify that they
don’t carry the gene for vEDS.
EDS is a progressive condition throughout life, at different ages different criteria are used
to diagnose the condition. It was found that the joint hypermobility that is commonly associated
with EDS fades as the individual reaches adulthood, but as joint mobility decreases, joint
instability and pain increases (Castori, Sperduti, Celletti, Camerota & Grammatico, 2011;
Castori, 2012). What that means is basically when an individual with EDS is young they have an
expanded the range of motion, but through repeated trauma, to the joints from repeated injury,
their range of motion becomes more normal but more prone to chronic pain and spontaneous
dislocations as they get older.
 One of the cruel jokes nature has played with this condition is that the typical approaches
modern medicine wants to take are far less effective. The condition reduces the effectiveness of
anesthetics and most painkillers to the point where doubling the dose is recommended (Castori,
2012). Pharmacological pain management is difficult in EDS. The joint instability results in
inflammation, but it also requires muscles to pick up the slack where the connective tissues are
unable to. This results in additional strain on the muscles of the body. Due to this muscle
relaxants are not recommended for longterm use as they increase the likelihood of further injury
(Zhou, Rewari & Shanthanna, 2018). The current Pharmacological suggestions involve the use
of anti-inflammatory drugs combined with large doses of painkillers (Zhou, Rewari &
Shanthanna, 2018). Opioids are considered to be effective for treating the pain but are not
recommended for long term use. There is some anecdotal evidence that medical marijuana might
be a better option long term but further research is required to be certain (Zhou, Rewari &
Shanthanna, 2018). The use of pharmaceuticals are only one part of the pain management
approach for EDS, a common method of treatment is using external devices to restrict the
individuals range of motion to prevent injury (Zhou, Rewari & Shanthanna, 2018)
Currently, the approach to treating pain is to attempt to prevent further injury, the current
research on the topic suggests avoiding high impact exercises, careful weight loss, and the
avoidance of exercises that regularly push joints to their limits (Castori, 2012). What that means
is a focus on general healthy living that minimizes sudden impacts that may cause dislocations
and the avoidance activities like yoga that increase joint mobility.
There is no cure for EDS, as stated above current treatment is focused on maintenance
and minimalization of pain. There is however a potential cure for it with today's technology, that
is CRISPR. CRISPR is capable of deleting genes and replacing them with a new one (Liu,
Zhang, Liu & Cheng, 2017). There are currently concerns about potential side effects, a clinical
trial designed to target the gene for sickle cell disease was recently given the green light to
proceed with human trials (U.S National Library of Medicine, 2019). if this trial is successful a
similar technique could potentially be developed to target the genes for EDS.
Overall Eds is an extremely complex group of genetic disorders that has a massive impact
on the quality of life of people who suffer from it. Due to its pervasive nature in the body its
symptoms are widespread. The volume of research being generated on it is significant, though
most of that body is specific case studies about specific individuals.
 References
Barabas A. P. (1967). Heterogeneity of the Ehlers-Danlos syndrome: description of three clinical types
and a hypothesis to explain the basic defect(s). British medical journal, 2(5552), 612–613.
Beighton, P. (1970). Ehlers-Danlos Syndrome. Ann Rheum Dis., 29(3), 332-333.
Castori, M. (2012). Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary
Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations. ISRN
Dermatology, 2012, 1-22.
Castori, M., Sperduti, I., Celletti, C., Camerota, F., & Grammatico, P. (2011). Symptom and joint
mobility progression in the joint hypermobility syndrome. Clinical And Experimental
Rheumatology, 29(6), 998-1005.
Liu, C., Zhang, L., Liu, H., & Cheng, K. (2017). Delivery strategies of the CRISPR-Cas9 gene-editing
system for therapeutic applications. Journal Of Controlled Release, 266, 17-26.
Parapia, L., & Jackson, C. (2008). Ehlers-Danlos syndrome – a historical review. British Journal Of
Haematology, 141(1), 32-35.
Reinstein, E., Pimentel, M., Pariani, M., Nemec, S., Sokol, T., & Rimoin, D. (2012). Visceroptosis of
the bowel in the hypermobility type of Ehlers–Danlos syndrome: Presentation of a rare
manifestation and review of the literature. European Journal Of Medical Genetics, 55(10), 548-
551.
U.S National Library of Medcine. (2019). A Safety and Efficacy Study Evaluating CTX001 in Subjects
With Severe Sickle Cell Disease. National Institutes of Health.
Zhou, Z., Rewari, A., & Shanthanna, H. (2018). Management of chronic pain in Ehlers–Danlos
syndrome. Medicine, 97(45), e13115.