Saturday, April 8, 2017

Liberty The Ehlers Danlos Dog

The book Liberty The Ehlers Danlos Dog is done and ready to purchase! Liberty and I wrote a book for kids that have EDS to help them explain a little about EDS to their friends and classmates. Liberty also explains what an Emotional Support Dog is and what she does to help me.
We are very excited about this and can't wait to help kids.
Take a look give us a like while you're there!

Click on this link or copy and paste it into your address bar!!
https://www.createspace.com/7028884


Liberty the Ehlers Danlos Dog shares a genetic disorder with her owner called Ehlers Danlos Syndrome. This is Liberty's story about what it is like to live with EDS and how she, an Emotional Support Dog, helps her owner. Liberty's story will help children who have Ehlers Danlos Syndrome not only understand better what EDS is but how to explain it to friends and family along with helping to educate others about the EDS child's special needs when at play or participating in sports.

This book is a great tool to help your child at the beginning of the school year introduce themselves with some of their challenges to their classmates and teachers.

Monday, May 23, 2016

The Website The Mighty Is Helping Me Explain A Little Bit About What Having EDS Feels Like

NO, This is not all in your head!!!  If you have or think that you might have Ehlers Danlos Syndrome then don't let those around you who are not inside your body and not feeling what your body is feeling tell you that the things going on with you are not real. Of course no one else can be inside your body and feel what you feel which is the point that I am trying to make to hopefully help you feel like you are not going crazy. So many things hurt and are out of balance and wack or whatever you want to call it when you have EDS and it seems unreal to those who are not suffering with it as a matter of fact, it seems unreal to those of us who are suffering it. I often find myself saying that if I lived on a planet full of people who had EDS that I would be completely normal but since I don't I have to look at things with different eyes than the average person. Knowing this, on some days, is more than half of the battle of just getting me through the day, and sometimes just through the hour.  Having others like myself to depend on helps in lots of ways and being able to describe how living with EDS feels so that others can know what I'm going through really really helps me feel part of a community these days. I often don't feel part of my regular community anymore and feeling isolated is once of the first steps to depression for me.

I was looking for something to help me explain to others and I found a great site called The Mighty its a great place to find support and information about being disabled and finding others who are dealing with some of the same issues that you do if you were to find yourself on that list.

Here is a post they have that has helped me feel better about myself and my situation.


http://themighty.com/2016/02/what-ehlers-danlos-syndrome-feels-like/

02/20/16
29 People With Ehlers-Danlos Syndrome Explain What It Feels Like



Ehlers-Danlos syndrome (EDS) is a group of connective tissue gene disorders, and symptoms include skin that tears or bruises easily and unstable joints prone to frequent dislocations, among other issues.

EDS affects somewhere between 1 in 2,500 to 1 in 5,000 people in the United States, but understanding of the disorder tends to be limited among society and medical professionals. Some individuals with EDS remark that their doctors don’t even know how to spell it, and the most common analogy likens the body of someone with EDS to that of a house built with faulty materials.

“Our EDS community formed out of a need to understand ourselves even when medical professionals did not,” a spokesperson for the Ehlers-Danlos National Foundation told The Mighty. “Awareness about EDS leads to better lives. Although EDS is not curable, early diagnosis can limit long-term damage as problems can be treated as they arise, and sharing information in our communities about what has worked for each of us can help all of us.”

We teamed up with the Ehlers-Danlos National Foundation to ask their Facebook community how they would describe the disorder to someone who doesn’t have it.

Here’s what they had to say:

1. “It feels like I’m 80 when I’m 40.” —Kimberly A. Bates



2. “It feels like having the flu all the time.” —Linnie Lin



3. “I feel like an alien on a planet where I don’t belong.” —Yolanda Smith

4. “It feels like I’m slowly disintegrating into particles…” —Sarah-Marie Zeraphic-McFarlane



5. “It feels like my body is falling apart at every joint.” —Breanna Griggs-Meloy

6. “It’s like a big pair of knickers with no elastic left.” —Christine Di Ciacca



7. “It’s like having the flu, a hangover and getting hit by a bus all at the same time.” —Irene Beck

8. “I feel like a marionette and someone else is in charge of the way I move.” —Nicole Hess



9. “It feels like your body is trying to turn itself inside-out, piece by piece.” —Aria Eragon

10. “It feels like I’m made of rubber bands that are about to snap.” —Katie Thomson



11. “It feels like you’ve lifted a car off someone all day every day.”—Melissa Conder

12. “It’s like an old house, creaking, squeaking swaying, and popping in the night, the wooden walls and nails coming apart at the slightest breeze.” —London Elaine Ridenour

13. “It’s like riding a bicycle with very loose bolts. You have to hold it together yourself or else it will fall apart.” —Melissa Drennan



14. “EDS is living the day after a car accident in perpetuity.” —Sabrina Winchester



15. “The pain is like sand paper being wiped on the inside of your skin all the time.” —Tiffani Rinzel

16. “You cannot trust your body to do what it is supposed to do.” —Emma Stathopoulos



17. “It’s like trying to build a tower out of misshapen blocks, where the tower is your body and the blocks are faulty collagen.” —Courtney Simonds

18. “The hair on my skin hurts.” —Mary Carlson



19. “You feel like you are constantly disappointing people because you have to cancel plans at the last minute when you are in too much pain, too sick, or too depressed to leave your house.” —Lisa Allison



20. “A 3 on a pain scale of 1-10 is a good day.” —Laurie Bohanan

21. “I feel like I’m falling apart at the seams.” —Lisa Sinnott



22. “EDS is feeling ‘insane’ for years because people tell you there is nothing physically wrong when youknow there is.” —Sarah Elizabeth Erwin Bloom

23. “You have to deal with the idea that your body is basically falling apart and there’s nothing you can do to stop it.” —Erin Geerlof

24. “EDS is the hypochondriac’s disease — always being questioned about whether or not you’re really in pain, or if everything wrong with you is really connected or not.“ —Sage Schultz

25. “Dislocations are like walking on glass, not knowing when you’re going to get cut but you know it’s inevitably going to happen. It sparks an unnatural fear that is hard to live with.” —Ariel Amberg



26. “The cruelest symptom of our illness is disbelief by medical personnel.” —Mary Carlson



27. “It’s like falling down the up escalator indefinitely while bystanders speculate about how you got there, what your injuries might be, and if you really even look hurt.” —Jess Elsen



28. “It’s like having everything in your body short circuit.” —EmJ Jackle-Hugh

29. “Day to day I feel like a stretchy rubber doll that’s working hard to stand up straight; bad days feel like I’ve been hit by a car, but the good days make me feel like I can still conquer the world!” —Beverly Wilson



Some answers have been edited for brevity and clarity.



Elisabeth Brentano

http://themighty.com/author/elisabeth-brentano/

What If No One Had Ever Heard Of Cancer And Would You Treat Me With Concern If I Were Pushing Around An IV Pole?

Can you think back to a time when no one knew what cancer was, me either because as long as I've been alive awareness of cancer and a search for a cure has been a focus of the public. But can you imagine if your loved ones were sick with cancer and you had never heard of cancer, would you be afraid of them, would you abandon them, would you be frustrated with them and tell them it's all in their head, would you tell them they'll have to do things on their own and would you not pray for them? Of course not and the reason is because we have all heard of cancer and we know what it can do to a body.

People raise awareness for illnesses that don't have a cure so why don't all the illnesses in that category get awareness shoutouts? I happen to have four illnesses that have no cure or treatment. This is the case with patients that have Ehlers-Danlos Syndrome, it causes other illnesses that have no cure or treatment so dealing with everyday life becomes impossible at best on many days however; we have some type of strength inside of us that we just keep on taking each day as it comes.

I have often been told that people don't understand what is wrong with me because they know I have something that they have never heard of before and because people are afraid of the unknown often times questions are not asked for better understanding. I have often also been told that if I were bald and pushing around an IV Pole that people would be bringing me potluck dinners and praying for me. Well, that's the truth as I have seen it first hand with family and friends who have had to fight through cancer.  Guess what?  I do push around and IV pole 18hrs a week while I get IV fluids to help my body think that it has more blood, since I have up to 15-20% less blood than the average person. Tricking my body into thinking that it has more blood help my heart not have to work so hard to pump blood through my body that basically flows backwards because of EDS which has caused a condition called Postural Orthostatic Tachycardia Syndrome. I also get IV's three days a week because EDS, and POTS causes me to be chronically dehydrated and the fluids only help me for about 24-36 hours before I need more. IV fluids also help me deal with Mast Cell Activation Disorder so I am able to put a band aide on three different problems that have not other treatment although the IV's are not really a treatment since a treatment is something that will cause the problem to go away. 

Getting IV's puts me in an infusion room where I see all kinds of illness from infection to liver and kidney failure and cancer and myself with only one other person that I have met in three years with the same conditions as myself. I have seen 100's of people come and go through the infusion room in these past few years and I have made and lost many friends to cancer and other illnesses during this time. I by no way want to belittle the impact that cancer has on a person or a family. I have learned through these past few years something about cancer compared to all the other illnesses I have seen come through the infusion room. 

A few lessons that I have learned: 
1. Cancer has no age restriction, 
2. The majority of the cancer patients that I have met have never dealt with a lot of illness and lots of them are experiencing illness for the first time in their lives, 
3. For the most part, a diagnosis of cancer lets you know at the beginning of your treatment what your possible outcome will be and how well or not you might handle that treatment, 
4. People hear the C word and they come running out of the woodworks to help you out, cleaning for the patient or family, cooking for them, driving them to treatment, sitting with them through treatment, bringing them lunch at treatment and all sorts of things that are needed when you are stuck at the hospital getting treatments, I rarely ever see someone with cancer coming into the treatment room completely alone, 
5. Friends and family post all over their facebook pages to please pray for the patient and please spread the word to help to find a cure for cancer, 
6. Pastors sometimes come to the infusion room to pray with their patients, 
7. Nurses in hospital settings are more sympathetic and empathetic to patients with cancer than other illness that bring people into the infusion rooms, 
8. Cancer patients can have really bad days during their treatments where they feel just their worst, but so do the other patients in the infusion room, 
9. Cancer patients who have not dealt with illness have a hard time dealing with their cancer because they don't know what it's like to have their lives interrupted with doctors appointments and infusions and accepting people helping them with everyday life, 
10. Everyone in the infusion room wants to talk about their illness and once the cancer patient has shared about their illness they then ask me about mine and when I explain just the EDS part and not even getting to the 25+ other illnesses that I have because that's what EDS gives you,  they begin to feel better about their journey and they ask who helps me with life and I respond no one, then they are really encouraged to see me helping myself in the infusion room to the restroom, getting my own lunch and blankets and that fact that I am still smiling and telling jokes, they almost always respond by saying that if I can do what I do than they can make it through what they are going through. 

As much as I hate that anyone has to go to the infusion room for anything, I am glad that I can encourage others and I'm also glad that EDS patients are really good at hiding what is going on inside physically and emotionally. If it weren't for that strength or maybe sometimes it's a weakness, my gig would be up and I would not be encouraging anyone. 
  
The person with Ehlers-Danlos has lived their whole lives being strong and has multiple things wrong with them, not just one diagnosis, and the EDS patient is very apt at accepting help, if it is ever offered which doesn't happen much in the EDS world at all because people don't understand the pain that comes with it and the fatigue, and the EDS patient lives their lives around doctor's appointment schedules and does so alone, driving themselves and coming home so exhausted, not only from chronic fatigue but also chronic pain that never leaves, that they will often have to go straight to bed without the laundry getting done, the trash being taking out, or a meal prepared for them but yet EDSers get right back up the next day and do it all over again and again learning how to ignore what needs to be ignored, (those things that drive a person crazy like a messy room) and pay attention to the important things like how to walk across the room and not dislocate something.  

Many will say that at this point I am just complaining and to you it may seem so. To me, I am just stating the facts and telling the truth. I have learned a lesson in this as well, many people cannot handle hearing the truth so instead of saying something simple like I'm uncomfortable hearing about how hard your life is" or "I'm scared for you and don't know how to help you", they cut you off and tell you to get it together and stop complaining...... oh sorry, just a jogged memory there....   If you happen to be one that doesn't understand chronic illness then this may seem harsh of me to say or you do just think I am complaining then I would suggest that you need to take a long look at your day to day life and pay attention to the things that irritate you or that you get upset by in your life and imagine yourself going through your day with one foot and a hand tied behind your back and see how much you can still do and look at yourself in the mirror at the end of the day and see if you have a smile to offer to someone or an encouraging word. A life with Ehlers-Danlos Syndrome is not for the faint of heart or the weak in spirit. If nothing else then let those of us who have reasons to be patients in an infusion room encourage you to not take yourselves so seriously.   


 I have been posting a lot of things about Ehlers-Danlos syndrome this week and that's because it's Ehlers-Danlos awareness month. I'm doing this obviously to raise awareness because it is a rare disease that many people have never heard of, including doctors. I am not posting things about Ehlers-Danlos syndrome for someone to feel sorry for me but rather I want to raise my voice that Ehlers-Danlos is real and it changes your life and it can rob you of your future. I don't like to ask for help and I get embarrassed having so many illnesses. I come from a family of overcomers and you just don't let illness keep you from things, but that is impossible with EDS and so I am admitting that I am not an overcomer when it comes to EDS, and I do have to ask for help. So I am asking, could you please share this blog or the video in this blog or even just the name EHLERS DANLOS SYNDROME with someone in your life today to help spread awareness about this illness that destroys lives, it kills, it robs and it tears families and friends apart. It's not the type of illness that gets it's victims help and support and acceptance and world wide prayer chains started, and kindness, and home health care and disability coverage and national campaigns and so the list goes one but it is the type of illness that needs all of these things and much much more. 





https://www.youtube.com/watch?v=8Q4juCB2GeU
This woman's story is the story of all people with Ehlers-Danlos syndrome.

Most people with Ehlers-Danlos syndrome do have heart defects like she does, I myself have a hole in my heart along with four other heart defects.

Most people with Ehlers-Danlos syndrome have to give up activities and social events, I myself have to sit out many times when my friends gather.

Most people with Ehlers-Danlos syndrome cannot do what they used to anymore, I myself can no longer play the piano or play my saxophone as it hurts my hands and arms and back too much to sit with my instruments, this is very sad to me as my music was a way to express my feelings and to worship God with the talents he gave me, I myself can no longer hold a book to read, it hurts my hands they cramp and sometimes my wrists dislocate or a finger will dislocate while holding the book. My favorite book of all I can no longer hold which is my Bible so I don't carry it to church with me, when I feel well enough to attend, I take an electronic Bible.

Most people with Ehlers-Danlos syndrome are not believed, I myself was told that it's just growing pains you will get over it or everybody hurts now and then, or it is impossible for someone to hurt that much, no one understands the pain that we are really in.

Most people with Ehlers-Danlos syndrome go to many doctors and spend a large portion of their life never knowing what's wrong with them, I myself see over 19 doctors and that's because all the doctors specialize in just one thing, and I was not diagnosed until I was 44 years old. Once you receive the diagnosis of Ehlers-Danlos syndrome you have to have every body part checked, every organ checked, because our collagen is week, it's possible to die from what would be a simple problem for most people if it's not taken care of. Once diagnosed you also find out if there are many other diseases that you have because of Ehlers-Danlos syndrome.

Most people with Ehlers-Danlos syndrome are very sick even though they look just fine, I myself am very sick and some days I cannot even take care my basic needs although I look perfectly healthy. But if you really pay attention you can see the fatigue on my face, my red cheeks from poor blood circulation, or a fever, the straining and caution with my movements.

Most people with Ehlers-Danlos syndrome have to go to the emergency room often, I myself sometimes have to go several times a month and then there are times when I might not go for a month or two. For us it is very frustrating to go to the ER because many of the doctors that you see in the ER don't know what Ehlers-Danlos is and you are treated as if you are a freak or someone just looking for attention.

Most people with Ehlers-Danlos syndrome are often abandoned by their friends and forgoten about, I myself have some relationships that have suffered because very few of my friends have researched or ask me what Ehlers-Danlos is. Because I don't have a disease that people know about others are uncomfortable talking about it, they don't know what to expect from my disease or how to support me. I can think of many ways to help me.

Most people with Ehlers-Danlos syndrome are afraid of the future, I myself am afraid that I will be left alone since I have no husband or children. I myself am afraid of how I'm going to take care of myself, I'm afraid that I will lose the ability to walk as I have already lost the ability to cook and clean like I want to.

Most people with Ehlers-Danlos syndrome have anxiety and depression, I myself have lots of depression and I often feel suicidal because I am afraid of my future and my pain on most days is just too much to handle, and I have lots of anxiety about what's going to happen to me and also if what I'm doing is going to dislocated joints and cause more pain. Sometimes I have anxiety about going to the doctor's appointments alone and understanding everything they tell me if they're even going to know what's wrong with me in the first place.

Most people with Ehlers-Danlos syndrome have chronic fatigue, I myself have chronic fatigue, there are days when I cannot wake up no matter what, and then there are days that I'm so exhausted that I cannot go to sleep because my pain is too great to rest.

Most people with Ehlers-Danlos syndrome just need someone to understand, I myself need someone to understand that I cannot stop thinking about Ehlers-Danlos syndrome as it affects every single second of my life no matter what I'm doing I am in constant pain, there is never a break from pain, I need someone to understand that I need to sometimes talk about what is going on with me and my body, and that I need to talk about my fears and my concerns, and I need someone to understand that I'm not being negative when I'm depressed and I'm not being negative when I talk about my health issues. I need someone to understand that even though my voice sounds happy or my voice sounds like I feel good that I really don't feel good, but I can still feel happy and not feel good. I need someone to understand that I can't change my disease or how I'm feeling by suggestions that are made to better my health, I have tried lots and lots of things and believe me if those things helped I would be doing them. I need someone to understand that I don't need to be fixed but instead I need someone to say I'm sorry this is happening to you and I'll pray for you.

Sunday, May 15, 2016

If You Have Ehlers Danlos Syndrome You Will Totally Get It, If You Don't Have EDS Check Out This Article To See If You Can Find An Answer To Your Chronic Illness Here.



Blogging Blogging Blogging! How important it is and how much I'm preaching to myself here. I need to be more disciplined about sending out information on Ehlers Danlos Syndrome so that others may find people in their lives, or themselves, or maybe even medical professionals may find some of their patients in these pages. Well, that is a big goal that I have set for myself since I hardly ever feel liking blogging. I don't like to blog when I don't feel well because I know I won't be at my best but, thank goodness there are others with EDS that blog as well. Together we all share the need to send a bright shining light into the medical community that EDS is alive and well and missed when all of the MANY illness that it causes shows up in the offices of doctors.

I ran across a blog post from http://chronicillnessproblems.tumblr.com/post/87429414675/thinking-you-might-have-ehlers-danlos-syndrome who had a great article about what EDS looks like.

Here is a list of some signs of EDS and some of the things that EDS causes in the EDS patient. I'm going to highlight the ones that I deal with just so you can see some of what I deal with on a daily basis. This is not a complete list by any means but hopefully it will give you the reality of why finding out information about EDS is so important for those who suffer with it.

 Other signs of Ehlers-Danlos include:
-Easily visible veins, especially on thighs, chest, or abdomen.
-“Transluscent” skin that can be described as especially soft, or “velvety.”
-Skin that bruises easily
-Blue sclera - that is when the whites of your eyes have a blue tent to them.   Yes, these are my eyes...... They are blue sometimes and green at other times. You can see the blue sclera in the eye on the left side of the picture, just in the outer edge.



The two pictures below I know are gross looking, I was feeling bad this day so the blood vessels in my eyes were bright red which I have noticed happens when I don't feel well. The blue sclera can be clearly seen when I turn my eyes all the way to the outside of my eye socket.  Here is the right eye                                   and here is the left eye. 









-Antimongoloid slant - this is a downward slanting of outside corner of the eyes.   My eyes are almost half moon shaped. 

-Pectus Excavatum - also known as sunken or funnel chest
-Flat feet
-Scoliosis (congenital or developed) - for now mine is mild in my lower back
-Marfanoid Habitus- a constellation of symptoms resembling those of Marfan syndrome, including long limbs, with an arm span that exceeds the height of the individual, and a crowded oral maxilla, sometimes with a high arch in the palate, arachnodactyly - condition in which the fingers and toes are abnormally long and slender, in comparison to the palm , and hyperlaxity- In such conditions as Ehlers Danlos or Marfan's syndrome, the connective tissue, which is the basic building block for ligaments, joint capsule and tendons, is abnormal.
-Mitral Valve Prolapse (though the especial frequency of this in EDS has been disputed in recent literature)
-Myopia - A condition in which close objects appear clearly, but far ones don't.This is not just a condition of getting older, and at times for me I can't see anything close up or far away without it all being very blurry.
-Abnormal orthodontics (severe overcrowding, losing baby teeth at late age.)
-Temporomandibular Joint Disorder
-Loss of proprioception - The unconscious perception of movement and spatial orientation arising from stimuli within the body itself. In humans, these stimuli are detected by nerves within the body itself, as well as by the semicircular canals of the inner ear. The American Heritage® Science Dictionary.  This one is tough for me because I am always running into things and misjudging where my arms and legs are and when I am standing up I have trouble knowing where my feet are on the floor. I often just kind of tip over or stumble as I walk and stand. I've gotten really good at catching myself from falling. 

Conditions that Frequently Co-exist or are caused by Ehlers Danlos:
Adrenal Insufficiency - a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol
Anxiety Disorders and Panic Attacks (result of Dysautonomia and the dysfunction of the para/sympathetic nervous system, and/or Adrenal Insufficiency)
Autoimmune Disorders (Esp. Thyroid related)
Arthritis
Carpal Tunnel Syndrome

Celiac Disease
Chiari Malformation -A condition in which brain tissue extends into the spinal canal that can cause problems with balance and coordination. It happens in people with EDS because the fluid from the brain doesn't drain properly so there is extra pressure on the brain forcing it downward so that the cerebellum rests on the spinal column. Chiari can happen in people without a visual sign of the cerebellum resting on the spinal column which is called Chiari Zero.
Chronic Cerebrospinal Venous Insufficiency - a condition where people have obstructed blood flow in the veins that drain the central nervous system (the brain and spinal cord). This can cause Chiari in EDS patients. Research indicates that CCSVI is significantly correlated with multiple sclerosis. As a result of these venous abnormalities, the blood flow rate through the central nervous system back toward the heart may become slowed, and blood may reflux back toward the brain and spine.
Chronic Fatigue (and Immune Deficiency) Syndrome
Chronic regional pain syndrome
Chron’s disease
Craniocervical Instability or Craniovertebral instability
Dysatuonimia - a malfunction of the Autonomic Nervous System
Early onset herniated disks or spinal degeneration
Fibromyalgia Syndrome
Fixed dystonia - abnormal posture even at rest
Gastroparesis (delayed gastric emptying)
Headache associated with cerebrospinal fluid leakage
Heart Murmur
Hiatus hernia
Immunological Deficiencies
Insufficient REM sleep (related to insomnia, breathing difficulties, etc.)
Irratible Bowel Syndrome

Kyphosis- especially of cervical Spine
Mast Cell Activation Syndrome - a condition with signs and symptoms involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems. Earlier proposed criteria for the diagnosis of MCAS included episodic symptoms consistent with mast cell mediator release affecting two or more organ systems with urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope or near syncope, tachycardia, wheezing, conjunctival injection, pruritus, and nasal stuffiness. This is kind of like being allergic to anything and everything but not everytime nor do you know when that time may be or not. 
Mitral Valve Prolapse
Multiple Sclerosis - highly suspected but not yet confirmed for me. 
Osteoporosis (or osteopenia)
Postural Orthostatic Tachycardia Syndrome (POTS)- 
a condition in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, called tachycardia. Other symptoms of an orthostatic nature — occurring in response to upright posture — may accompany the tachycardia. EDS patients, or at least how it was explained to me about myself, do not retain fluid they take in. I was told that the cells in my body, because of the EDS are the wrong shape to hold in salt which causes me to not retain fluid so therefore, I am always dehydrated and I will always be dehydrated no matter how much water I drink. I have ended the week of getting IV's and ended up in the ER and tested for dehydration and was show to be dehydrated. It happens everytime I get my blood checked. The saline IV's help me feel a little better for about 24-36 hours but after that I feel myself sinking so to speak and my mood changes, not for the better and I become more dizzy and tired. Patients with POTS are known to have up to 20% less blood volume than the normal person causing the heart to overwork to compensate. POTS is very tiring to the body and is compared to using as much energy as it would take to run on a treadmill 24 hours a day 7 days a week non-stop or like someone who has congestive heart failure. For the EDS patient once you have POTS you will have it for life. There is no cure for POTS although there are some instances a person can develop POTS and then they will cease to have it. The only help for POTS is to try and control the symptoms, which you never know when they will hit, with saline IV's and certain heart medications that may slow the symptoms. I spend 18 hrs a week at the hospital getting saline IV's to help my heart not have to work so hard which below you will read about my heart and how important that is for me. Saline IV's are also said to help support patients with Mast Cell Activation Disorder.
Scoliosis, usually congenital
Temporomandibular Joint Disorder
Tendinitis

Tethered Cord Syndrome
Vitamin Deficiencies (malabsorption) (Esp. B, and D)  

These were not on the list that I found on the blog post below but I included them because the are all caused from EDS. The heart stuff gets pretty scary if you ask me.
Arterial Fibrillation
PFO grade III - A patent foramen ovale (PFO) is a persistent, usually flap-like opening
Tricuspid Regurgitation - a disorder in which the heart's tricuspidvalve does not close properly, causing blood to flow backward (leak) into the right upper heart chamber (atrium) when the right lower heart chamber (ventricle) contracts
Mitral Regurgitation-leakage of blood backward through the mitral valve each time the left ventricle contracts. A leaking mitral valve allows blood to flow in two directions during the contraction.
ASD -Atrial Septal Defect - a hole in the heart
ASA - Atrial Septal Aneurysm - a rare but well recognized and localized saccular deformity of the atrial septum that bulges into the right or left atrium with uncertain clinical significance.

This sounds like a lot doesn't it? Well, ask anyone with Ehlers Danlos and they will tell you that this just scratches the surface. Having so many things wrong with our bodies is because this is a collagen disorder and since the human body is made up of about 80% collagen, when you make faulty collagen it messes with every single system of the human body. Another reason that I blog about EDS is because I want my friends to understand that when I say I don't feel good, I don't mean that I'm a little tired or that my stomach hurts, I mean at least 90% of my body doesn't feel good at any given moment. 

There are some great facts and info in the blog chronicilnessproblems and you can look for yourself there or someone you may know who seems to be chronically ill but yet never finds an answer to what is causing the problems.

Giving all the credit to Chronicilnessproblems here is the blog post copied and pasted here.

Thinking You Might Have Ehlers-Danlos Syndrome?

Unlike many heritable connective tissue disorders (HCTD,) there isn’t a genetic test for most types of EDS. There is a test for Vascular type, but it isn’t 100% accurate, and there is a test for Classic, but it’s only about 50% accurate. So the diagnosis for Ehlers-Danlos Syndrome is generally made by the Beighton, Brigton, and sometimes the Villefranches criteria, and by history and family history questioning done by a geneticist.

Decades ago, Ehlers-Danlos was estimated to affect 1 in 10,000 people, for the most common type. Now, it is estimated that Ehlers-Danlos Hypermobility Type is at least twice that common, and that still three-quarters of cases go undiagnosed, due to poor education and awareness about the Syndrome. Many doctors who do diagnose EDS fail to recognize the less common types, and some with the other types are misdiagnosed as Hypermobility type.

Beighton and Brighton Criteria for EDS Hypermobility Type:




The Beighton Scale:
The Beighton scale is scored from 1-9, and measures hypermobility. As is pictured, you get one point for each: pinky that can bend back past 90 degrees, each thumb that can touch your wrist, each elbow that bends backwards, knee that bends backwards, and one point if you can press the palms of your hands to the floor without bending your knees.
(0-2 points = not significantly hypermobile, 3-4 points = moderately hypermobile, 5-9 points = distinctly hypermobile)
A score of 4 is generally considered hypermobile in practice. Many people can do one to a few of these, which isn’t abnormal, but 4 will be classified as hypermobile.

The Brighton criteria:
Major Criteria-
-A Beighton score of 4/9 or greater (either currently or historically.)
-Arthralgia (joint pain) for longer than 3 months in 4 or more joints.

Minor Criteria-
-A Beighton score of 1, 2 or 3. (0, 1, 2, or 3 if aged 50+)
-Arthralgia for more than three months in one to three joints or back pain for more than three months, and/or spondylosis/spondylolysis/spondylolisthesis
-Dislocation or subluxation in more than one joint, or in one joint more than once
-soft tissue rheumatism. greater than 3 soft tissue lesions (bursitis, etc.)
-Marfanoid habitus (tall, slim, span/height ratio >1.03, upper: lower segment ratio less than 0.89, arachnodactyly (positive Steinberg/wrist signs)
-Abnormal skin, striae, hyper extensibility, thin skin, papyraceous scarring.
-Eye signs: drooping eyelids or myopia or antimongoloid slant
-Varicose veins or hernia or uterine/rectal prolapse

Ehlers-Danlos (or Joint Hypermobility Syndrome) is diagnosed in the presence of:
-Two major criteria OR
-One major and two minor criteria OR
-Four minor criteria OR
-Two minor criteria IF a first-degree relative is unequivocally affected

This is what doctors and researchers use to classify Ehlers-Danlos Syndrome. They will also, especially in types other than Type 3- Hypermobility type, look at family history of hypermobility of sudden death due to organ or vessel rupture, at scoliosis, presence of skin fragility or elastic skin, organ fragility, or related conditions.

The Beighton and Brighton generally are used to diagnose the Hypermobility type, and in 1997, a group of experts met in Villefranche and developed the Villefranche criteria. This criteria also includes important aspects for the other types of Ehlers Danlos.

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Other signs of Ehlers-Danlos include:
-Easily visible veins, especially on thighs, chest, or abdomen.
-“Transluscent” skin that can be described as especially soft, or “velvety.”
-Skin that bruises easily
-Blue sclera
-Antimongoloid slant
-Pectus Excavatum
-Flat feet
-Scoliosis (congenital or developed)
-Marfanoid Habitus
-Mitral Valve Prolapse (though the especial frequency of this in EDS has been disputed in recent literature)
-Myopia
-Abnormal orthodontics (severe overcrowding, losing baby teeth at late age.)
-Temporomandibular Joint Disorder
-Loss of proprioception

Conditions that Frequently Co-exist or are caused by Ehlers Danlos:
Adrenal Insufficiency
Anxiety Disorders and Panic Attacks (result of Dysautonomia and the dysfunction of the para/sympathetic nervous system, and/or Adrenal Insufficiency)
Autoimmune Disorders (Esp. Thyroid related)
Arthritis
Carpal Tunnel Syndrome
Celiac Disease
Chiari Malformation
Chronic Cerebrospinal Venous Insufficiency
Chronic Fatigue (and Immune Deficiency) Syndrome
Chronic regional pain syndrome
Chron’s disease
Craniocervical Instability or Craniovertebral instability
Dysatuonimia
Early onset herniated disks or spinal degeneration
Fibromyalgia Syndrome
Fixed dystonia
Gastroparesis (delayed gastric emptying)
Headache associated with cerebrospinal fluid leakage
Heart Murmur
Hiatus hernia
Immunological Deficiencies
Insufficient REM sleep (related to insomnia, breathing difficulties, etc.)
Irratible Bowel Syndrome
Kyphosis- especially of cervical Spine
Mast Cell Activation Syndrome
Mitral Valve Prolapse
Multiple Sclerosis
Osteoporosis (or osteopenia)
Postural Orthostatic Tachycardia Syndrome
Scoliosis, usually congenital
Temporomandibular Joint Disorder
Tendinitis
Tethered Cord Syndrome
Vitamin Deficiencies (malabsorption) (Esp. B, and D)


If these criteria fit you, you may have Ehlers-Danlos Syndrome. Even if you’re close to the criteria and seeking a diagnosis, or if you have a family history of similar issues, it’s definitely worth looking into and being evaluated by a geneticist, because if not EDS, there are similar HCTDs. Geneticists are generally the best doctors to see for EDS, but rheumatologists can also be experienced in treating and diagnosing Ehlers-Danlos.

The Ehlers-Danlos National Foundation- EDNF- has a list of specialists by area here.
The biggest names are Dr. Clair Francomano and Dr. Brad Tinkle, and also in the Maryland area the Johns Hopkins doctors are good- Dr. Howard Levy is great, and Dr. Dietz is also good, especially for Vascular type, though his specialty is other HCTD, (Like the one he helped name, Loyez-Dietz Syndrome.)
Even a doctor who isn’t considered an “expert” can help diagnose Ehlers-Danlos and start the treatment process, but always be sure to do your own research and don’t believe everything a single doctor says.
(For example that EDS is “just a label” or that EDS “can’t really be treated anyway.”)

Research can be found through EDNF, NCBI Pubmed Studies (and other scientific websites like Journal of the American Osteopathic Assiciation,) and Pretty Ill, and any medical websites. Ones aimed at medical students or published medical studies and journals are better for information than discussion boards, but discussion boards can be helpful in their way, especially for psychosocial type support from the more positive ones.

Lastly, there is the question over differences between EDS Hypermobility type, Joint Hypermobility Syndrome, and Benign Joint Hypermobility Syndrome.
Benign JHS versus non-benign JHS is basically just asymptomatic (benign) versus Symptomatic. The only diagnostic criteria for Benign Hypermobility Syndrome is the Beighton Score of 4 or higher, but without any joint pain (arthralgia.)
There is much recent debate in literature and research over whether there is a difference in EDS Hypermobility Type (HT) and JHS. Some say that they are the same illness, since they are often seen in the same family (one member will be diagnosed with JHS and another with EDS,) indicating that the genotype for EDS HT and JHS is the same and hereditary. Others dispute this, saying that JHS is simply the joint hypermobility due to looser joints, and that JHS does not present with the same symptoms as EDS HT, such as skin involvement, appearance (translucent skin, blue sclera, high palate, pectus excavatum, etc.,) or the other systematic involvement that is frequently present in EDS like the autonomic dysfunction, gastroparesis, etc. This is frequently disputed, and likely will be until we discover the genes behind EDS HT and behind JHS, and are able to tell whether or not they are the same illness with a wide range of presentation, or different illnesses altogether.

Friday, May 13, 2016

Tips For Helping Reduce Pain For The EDS Patient In The Kitchen


Cooking! I don't care to do, nor do I need to that much. I am single and live alone, I have no children so cooking is not a must do activity for me. I used to like to bake but now that my EDS has progressed so far I really can't enjoy baking because the pain way out does the pleasure of the outcome of the baking. That's okay because that is less clean up for me.

I do have to eat and at times carry a lunch with me to places and doing so can be a challenge for me as well as for any EDS patient. I found a great article on tips of reducing pain in the kitchen. Here is the article  and the link: http://www.chronicpainpartners.com/reducing-pain-and-effort-in-the-kitchen/

Reducing Pain and Effort in the Kitchen
Jul 14, 2012

EDSers are often frustrated with kitchen implements – they may be ineffective, difficult to use, or downright painful! Opening jars, bottles and cans are high on the list of complaints. Slicing, peeling, and cutting with knives is often painful. Lifting heavy pots, especially those with long handles, create torque on the wrist that makes it prone to dislocations.

To address kitchen challenges, here are some tips and product suggestions presented by an occupational therapist at the 2011 EDS conference.

Try these helpful hints to reduce EDS pain in the kitchen:
• Use spring loaded scissors to cut open bags or to cut food
• Use ‘zipper’ style baggies
• Buy reusable containers that are easy to open/close
• Buy food pre-chopped or use a spiked cutting board
• Use large well sharpened knives and the right knife for the job
• Use oven mitts to help you carry heavy pots/pans with 2 hands
• Use tongs to lift foods instead of forks
• Put groceries in paper bags for 2 hand carry, or in reusable bags for carrying over shoulder or pack light and carry over forearms
• Use plastic cups and plates
• Use electric whenever possible for opening cans or jars, mixing, blending, chopping
• Use built up kitchen tools
• Use paper towels to avoid having to wring; or press sponge with palm rather than squeezing
• Use an ‘L’ shaped knife or pizza cutting wheel
• Put dycem or wet dishrag under bowls when stirring
• Drag pots filled with liquid to sink or stove. Use extensible kitchen faucet to fill pots
• Use stainless steel colander in pots to avoid having to tip out liquid
• Buy lightweight pots/containers

List Source: Joint Protection of the Hands, 2011 EDNF Conference Presentation by Romina Astifidis MS, PT, CHT. Excerpt from Helpful Hints, page 5.

As a fellow EDSer, I have a few tips of my own. A good option for lightweight cookware is stainless steel pans. Revere Ware is my personal favorite. They are copper bottom with a stainless steel inside, which is fairly easy to clean when you coat the bottom with olive oil. Also they are aluminum-free and Teflon-free, which is healthier.

I have a lot of trouble with scissors. My favorite scissors are Black & Decker electric scissors. I like them because they do not require me to open and close my hand. They have a large grip and maneuver easily. They work well for both the kitchen and office – cutting both plastic and paper with ease. They even cut material! They are cordless and rechargeable.

- See more at: http://www.chronicpainpartners.com/reducing-pain-and-effort-in-the-kitchen/#sthash.medseEUD.dpuf

Wednesday, July 22, 2015

A Clinical Description of Ehlers Danlos Syndrome Classical Type I & II

I have EDS Classical Type. They have now combined type one and two into one category which is now just called Classical Type.
Awareness is so important because of the signs that I had as a baby would have let my parents know to have me checked out and even more important, my Doctor would have known what was wrong with me.

My mother, of course having no knowledge of EDS, said that I was a very soft and floppy baby. Also, she said that I had a hard time learning how to walk and that I would kick out one leg with each step instead of just taking a normal step. These were just a very few of the things mentioned here that would have helped me in many many ways if we would have known what in the world EDS was. It would have helped me know how to protect myself during play and sports activities, it would have helped me understand why I just felt tired all the time and why I was dizzy and why my body seemed to hurt at times that my peers did not.
 
I hope that this information is helpful to those who are searching for information about EDS and also that with the links provided in the article it will help you reach deeper into the maze that is EDS in order to help get what you need to pass along awareness to others.  


http://www.ncbi.nlm.nih.gov/books/NBK1244/


Ehlers-Danlos Syndrome, Classic Type
Synonyms: Ehlers-Danlos Syndrome, Classical Type; EDS, Classic Type. Includes: Ehlers-Danlos Syndrome Type I, Ehlers-Danlos Syndrome Type II

Fransiska Malfait, MD, PhD, Richard Wenstrup, MD, and Anne De Paepe, MD, PhD.Author Information


Initial Posting: May 29, 2007; Last Update: August 18, 2011.
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Summary

Clinical characteristics.

Ehlers-Danlos syndrome (EDS), classic type is a connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility. It includes two previously designated subtypes (EDS type I and EDS type II) that are now recognized to form a continuum of clinical findings. The skin is smooth, velvety to the touch, and hyperelastic; i.e., it extends easily and snaps back after release (unlike lax, redundant skin, as in cutis laxa). The skin is fragile, as manifested by splitting of the dermis following relatively minor trauma, especially over pressure points (knees, elbows) and areas prone to trauma (shins, forehead, chin). Wound healing is delayed, and stretching of scars after apparently successful primary wound healing is characteristic. Complications of joint hypermobility, such as dislocations of the shoulder, patella, digits, hip, radius, and clavicle, usually resolve spontaneously or are easily managed by the affected individual. Other features include hypotonia with delayed motor development, fatigue and muscle cramps, and easy bruising. Less common findings include mitral and tricuspid valve prolapse, aortic root dilatation, and spontaneous rupture of large arteries.

Diagnosis/testing.

The diagnosis of EDS, classic type is established by family history and clinical examination. Quantitative and qualitative studies of type V collagen chains are usually not useful in confirming a diagnosis. At least 50% of individuals with classic EDS have an identifiable pathogenic variant in COL5A1 or COL5A2, the genes encoding type V collagen; however, this number may be an underestimate, since no prospective molecular studies of COL5A1 and COL5A2 have been performed in a clinically well-defined group.

Management.

Treatment of manifestations: Children with hypotonia and delayed motor development benefit from physiotherapy. Non-weight-bearing exercise promotes muscle strength and coordination. Anti-inflammatory drugs may alleviate joint pain. Those with hypotonia, joint instability, and chronic pain may need to adapt lifestyles accordingly. Dermal wounds are closed without tension, preferably in two layers. For other wounds, deep stitches are applied generously; cutaneous stitches are left in place twice as long as usual; and the borders of adjacent skin are carefully taped to prevent stretching of the scar. Cardiovascular problems are treated in a standard manner.

Prevention of primary manifestations: Young children with skin fragility can wear pads or bandages over the forehead, knees, and shins to avoid skin tears. Older children can wear soccer pads or ski stockings with shin padding during activities. Ascorbic acid (vitamin C) may reduce bruising.

Surveillance: Yearly echocardiogram when aortic dilatation and/or mitral valve prolapse are present.

Agents/circumstances to avoid: Acetylsalicylate; sports that strain joints.

Genetic counseling.

EDS, classic type is inherited in an autosomal dominant manner. It is estimated that approximately 50% of affected individuals have inherited the pathogenic variant from an affected parent, and approximately 50% of affected individuals have a de novo disease-causing mutation. Each child of an affected individual has a 50% chance of inheriting the mutation. Prenatal testing for pregnancies at increased risk is possible for families in which the pathogenic variant has been identified in an affected family member.
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Diagnosis

Clinical Diagnosis

The diagnosis of Ehlers-Danlos syndrome (EDS), classic type is established by family history and clinical examination. Diagnostic criteria were developed by a medical advisory group in a conference (sponsored by the Ehlers-Danlos Foundation [USA] and the Ehlers-Danlos Support Group [UK]) at Villefranche in 1997 [Beighton et al 1998] (full text; pdf).

The combination of the first three major diagnostic criteria should have a highspecificity for EDS, classic type. The presence of one or more minor criteria contributes to the diagnosis of EDS, classic type but is not sufficient to establish the diagnosis.

Major diagnostic criteria for the classic type of EDS
Skin hyperextensibility. Skin hyperextensibility (see Figure 1) should be tested at a neutral site (one not subjected to mechanical forces or scarring), such as the volar surface of the forearm. It is measured by pulling up the skin until resistance is felt. In young children, hyperextensibility of the skin is difficult to assess because of abundant subcutaneous fat.
Widened atrophic scars. (see Figure 2) (a manifestation of tissue fragility)
Joint hypermobility. Joint hypermobility (see Figure 3) depends on age, gender, and family as well as ethnic backgrounds. Joint hypermobility in classic EDS is general, affecting both large and small joints, and is usually noted when a child starts to walk. It should be assessed using the Beighton scale, the most widely accepted grading system for the objective semi-quantification of joint hypermobility (see Table 1).
Positive family history


Figure 1.

Skin hyperextensibility


Figure 2.

Widened atrophic scars


Figure 3.

Passive flexion of thumbs to the forearm: manifestation of joint hypermobility

Table 1.


Beighton's Criteria for Joint Hypermobility

Joint/FindingNegativeUnilateralBilateralPassive dorsiflexion of the 5th finger >90° 0 1 2
Passive flexion of thumbs to the forearm 0 1 2
Hyperextension of the elbows beyond 10° 0 1 2
Hyperextension of the knees beyond 10° 0 1 2
Forward flexion of the trunk with knees fully extended and palms resting on the floor 0 1



A total score of ≥5 defines hypermobility.

Minor diagnostic criteria for the classic type of EDS
Smooth, velvety skin
Molluscoid pseudotumors: fleshy, heaped-up lesions associated with scars over pressure points such as the elbows and knees
Subcutaneous spheroids: small, cyst-like, hard shot-like nodules, freely moveable in the subcutis over the bony prominences of the legs and arms. They occur in approximately one third of affected individuals, are numerous, and feel like hard grains of rice. X-ray reveals an outer calcified layer with a translucent core. The spheroids represent subcutaneous fat globules that have lost their blood supply, becoming fibrosed and calcified.
Complications of joint hypermobility (e.g., sprains, dislocations/subluxations, pes planus)
Muscle hypotonia, delayed gross motor development
Easy bruising
Manifestations of tissue extensibility and fragility (e.g., hiatal hernia, anal prolapse in childhood, cervical insufficiency)
Surgical complications (postoperative hernias)

Testing

Electron microscopy of a skin biopsy in EDS, classic type often suggests disturbed collagen fibrillogenesis. A "cauliflower" deformity of collagen fibrils is characteristic [Hausser & Anton-Lamprecht 1994]. However, these findings are not specific for EDS and thus not diagnostic. Furthermore, ultrastructural changes, usually most pronounced in the central parts of the reticular dermis, may be missed if the skin biopsy is not full thickness.

Biochemical testing on cultured dermal fibroblasts. Collagen protein analysis is performed on cultured fibroblasts, derived from a skin biopsy in order to obtain a source of protein for electrophoretic analysis of collagen types I, III, and V. The collagens are labeled and analyzed on SDS-polyacrylamide gel electrophoresis. Abnormal proteins migrate differently on the gel when compared to control samples. Since type V collagen is synthesized by fibroblasts at low levels, alterations in electrophoretic mobility are poorly reproducible, making this an ineffective method for routine diagnostic evaluation. The test, however, helps to exclude other subtypes of EDS (e.g., the vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis types) in individuals in whom clinical differential diagnosis is difficult. Rarely, an abnormal electrophoretic pattern for type I collagen is detected due to the presence of an arginine-to-cysteine substitution inCOL1A1 coding for the proα1(I) collagen chain of type I collagen [Nuytinck et al 2000,Malfait et al 2007]

Molecular Genetic Testing

Genes. In the majority of affected families (≥50%), the pathogenic variant is identified in the genes encoding type V collagen, COL5A1 and COL5A2. However, since no prospective molecular studies of COL5A1 and COL5A2 have been performed in a clinically well-defined patient group, this number may underestimate the real proportion of individuals with classic EDS harboring a pathogenic variant in one of these genes.

Evidence for locus heterogeneity. A COL1A1 pathogenic variant, p.Arg134Cys, was identified in two unrelated children with classic EDS [Nuytinck et al 2000]. The same substitution was subsequently identified in three unrelated persons with aneurysms and rupture of medium-sized arteries in young adulthood. These people also had thin and hyperextensible skin, easy bruising, and abnormal wound healing [Malfait et al 2007; Malfait and De Paepe, personal observation]. Mutation of COL1A1, however, is not a major cause of classic EDS [Malfait et al 2005].

Clinical testing
Sequence analysis. Approximately 50% of individuals with classic EDS have an identifiable pathogenic variant in COL5A1 or COL5A2. COL5A1 null alleles are detected in approximately 30%-40% of individuals with classic EDS [Malfait et al 2005].
Deletion/duplication analysis. The usefulness of such testing has not been demonstrated, as no deletions or duplications involving COL5A1 or COL5A2 as causative of classic EDS have been reported.
COL5A1 null allele test. The COL5A1 null allele test determines if the individual is heterozygous for one of several COL5A1 polymorphic exonic markers in gDNA and then establishes at the cDNA level whether both alleles are expressed. If only one of the two COL5A1 alleles is present in cDNA, it is assumed that the absent allele is null. Since this test examines both gDNA and cDNA, COL5A1null allele testing requires cultured skin fibroblasts. It does not identify pathgoenic variants within COL5A1 [Malfait et al 2005].

Table 2.


Summary of Molecular Genetic Testing Used in Ehlers-Danlos Syndrome, Classic Type

Gene 1Proportion of EDS, Classic Type Attributed to Mutation of This GeneTest MethodMutations Detected 2COL5A1 46% 3 Sequence analysis 4 Sequence variants
Deletion/duplicationanalysis 5 Exonic and whole-genedeletions/duplications 6
COL5A2 4% 3 Sequence analysis 4 Sequence variants
Deletion/duplicationanalysis 5 Exonic and whole-genedeletions/duplications 6

1.

See Table A. Genes and Databases for chromosome locus and protein name.2.

See Molecular Genetics for information on allelic variants.3.

Malfait et al [2005], Malfait & De Paepe [2005]4.

Examples of pathogenic variants detected by sequence analysis include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exonic or whole-genedeletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.5.

Testing that identifies exonic or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probeamplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosomesegment.6.

No deletions or duplications involving COL5A1 or COL5A2 have been reported to cause Ehlers-Danlos syndrome, classic type. (Note: By definition, deletion/duplication analysis identifies rearrangements that are not identifiable by sequence analysis of genomic DNA.)

Test characteristics. See Clinical Utility Gene Card [Mayer et al 2013] for information on test characteristics including sensitivity and specificity.

Testing Strategy

To confirm/establish the diagnosis in a proband. Molecular genetic testing for classic EDS is complicated by the large number of exons in the coding sequences (66 inCOL5A1 and 52 in COL5A2) and the wide distribution of mutations. When a clinical diagnosis of classic EDS is suspected, we recommend the following evaluations:
Perform sequence analysis by Sanger sequencing of COL5A1 and COL5A2either on gDNA or cDNA. The authors recommend starting with sequence analysis of COL5A1 on gDNA, as most individuals with classic EDS harbor a unique pathogenic variant in this gene, leading to the introduction of a premature termination codon and nonsense-mediated decay of mRNA. When no COL5A1pathogenic variant is found, sequence analysis of COL5A2 should be performed.
Perform COL5A1 null allele test and biochemical testing. If sequence analysisof both COL5A1 and COL5A2 does not identify a causal variant in a person with the phenotype of classic EDS, the authors recommend obtaining a skin biopsy in order to perform a COL5A1 null allele test and biochemical testing.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the pathogenic variant in the family.

Genetically Related (Allelic) Disorders

No other phenotypes are associated with mutation of COL5A1 or COL5A2.
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Clinical Characteristics

Clinical Description

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility. Previously, two subtypes, EDS type I and EDS type II, differing only in phenotypic severity, were recognized; it is now apparent that they form a continuum of clinical findings.

Skin
Cutaneous hyperextensibility is one of the cardinal features of EDS in general and of classic EDS in particular. Skin extends easily and snaps back after release (unlike lax, redundant skin, as in cutis laxa).
The skin is smooth and velvety to the touch.
The skin is fragile, as manifested by splitting of the dermis following relatively minor trauma, especially over pressure points (knees, elbows) and areas prone to trauma (shins, forehead, chin). Skin fragility may cause dehiscence of sutured incisions in skin or mucosa.
Wound healing is delayed, and stretching of scars after apparently successful primary wound healing is characteristic. Scars become wide, with a "cigarette-paper"-like or papyraceous appearance.
Other dermatologic features in classic EDS:
Molluscoid pseudotumors (see Clinical Diagnosis)
Subcutaneous spheroids (see Clinical Diagnosis)
Piezogenic papules: small, painful, reversible herniations of underlying adipose tissue globules through the fascia into the dermis, such as on medial and lateral aspects of the feet upon standing
Elastosis perforans serpiginosa: a rare skin condition of unknown etiology characterized by skin-colored to erythematous keratotic papules, some enlarging outwards in serpiginous or arcuate configurations, leaving slightly atrophic centers
Acrocyanosis: a painless disorder caused by constriction or narrowing of the small blood vessels in the skin (affecting mainly the hands) in which the affected areas turn blue and become cold and sweaty; localized swelling may also occur
Chilblains: cold injuries, characterized by a red swollen skin that is tender, hot to the touch, and may itch; can develop in less than two hours in skin exposed to cold

Tissue fragility. Manifestations of generalized tissue extensibility and fragility are observed in multiple organs:
Cervical insufficiency during pregnancy
Inguinal and umbilical hernia
Hiatal and incisional hernia
Recurrent rectal prolapse in early childhood

Joints
Complications of joint hypermobility including dislocations of the shoulder, patella, digits, hip, radius, and clavicle may occur and usually resolve spontaneously or are easily managed by the affected individual. Some individuals with classic EDS may experience chronic joint and limb pain, despite normal skeletal radiographs.
Other problems related to the joint hypermobility are joint instability, foot deformities such as congenital clubfoot or pes planus, temporomandibular joint dysfunction, joint effusions, and osteoarthritis [Hagberg et al 2004, De Coster et al 2005a, De Coster et al 2005b].

Neurologic features. Primary muscular hypotonia may occur and may cause delayed motor development, problems with ambulation, and mild motor disturbance. Fatigue and muscle cramps are relatively frequent. Rarely, CSF leak has been reported to cause postural hypotension and headache in individuals with classic EDS [Schievink et al 2004].

Easy bruising. Easy bruising is a common finding and manifests as spontaneous ecchymoses, frequently recurring in the same areas and causing a characteristic brownish discoloration of the skin, especially in exposed areas such as shins and knees. There is a tendency toward prolonged bleeding (e.g., following brushing of the teeth) in spite of a normal coagulation status.

Cardiovascular
Structural cardiac malformations are uncommon in classic EDS.
Mitral valve prolapse and, less frequently, tricuspid valve prolapse may occur. Stringent criteria should be used for the diagnosis of mitral valve prolapse.
Aortic root dilatation may be more common than previously thought [Wenstrup et al 2002]. A recent retrospective study showed that three out of 50 (6%) individuals with classic EDS had aortic dilatation at their first echocardiogram, which was performed at a median age of 16 years. However, the dilatation tended to be of little clinical consequence and the mitral valve prolapse is rarely severe. Medical or surgical intervention is rarely necessary for either [Atzinger et al 2011].
Spontaneous rupture of large arteries, along with intracranial aneurysms and arteriovenous fistulae, may occur in the rare individual with a severe form of classic EDS.

Pregnancy in a woman with classic EDS bears risk for the newborn as well as for the mother. As a whole, these complications are more frequent than in the normal population; however, it is difficult to quantitate the incidence of each complication inaffected individuals because no good studies exist:
Premature rupture of the membranes and prematurity can occur when the mother is affected, and also when the fetus is affected, especially in the most severe forms.
Because of hypotonia, breech presentation is more frequent if the baby is affectedand may lead to dislocation of the hips or shoulder of the newborn.
In affected women, tearing of the perineal skin by forceps and, after delivery, extension of episiotomy incisions and prolapse of the uterus and/or bladder may occur.

Genotype-Phenotype Correlations

The number of individuals described with pathogenic variants in COL5A1 or COL5A2 is relatively small. Although there can be some variability in severity of the phenotype, nogenotype/phenotype correlations have emerged to date. In particular, no difference in severity is noted in individuals with a COL5A1 null mutation as compared to individuals with a structural mutation or those in whom no mutation can be detected.
Mutations in COL5A1 that encode the amino-terminal region of the proα1(V) collagen chain appear to be associated with a phenotype that can differ slightly from the classic EDS phenotype.
A p.Gly530Ser substitution in the amino-terminal propeptide of the α1(V) chain may be disease-modifying when present in the heterozygous state and disease-causing in the homozygous state [Giunta & Steinmann 2000, Giunta et al 2002].
A particular splice site mutation with a complex outcome within the amino-terminal region of the proα1(V) collagen chain was recently shown to result in a classic EDS-like phenotype with only minor cutaneous involvement (absence of the characteristic atrophic scarring) but with severe kyphoscoliosis and retinal detachment [Symoens et al 2011].

Penetrance

Inter- and intrafamilial variability in the severity of the phenotype can be great.

In some families with a non-functional (i.e., null) COL5A1 allele, an affected member can have a very mild classic EDS phenotype, while other family members may have a severe phenotype [Malfait & De Paepe 2005].

Anticipation

Anticipation is not observed.

Nomenclature

As a result of the 1997 Villefranche conference on EDS [Beighton et al 1998], the former EDS type I and type II are now reclassified as EDS, classic type.

Prevalence

The prevalence of EDS type I has been estimated at 1:20,000 [Byers 2001]. However, it is likely that some individuals with milder manifestations of the disease, previously classified as EDS type II, do not come to medical attention and thus go undetected.
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Differential Diagnosis

Other forms of Ehlers-Danlos syndrome (EDS) should be considered in individuals with easy bruising, joint hypermobility, and/or chronic joint dislocation. The disorders in which clinical findings overlap with the classic type of EDS include the following:

Ehlers-Danlos syndrome, hypermobility type (EDS type III). In this form, joint hypermobility is the primary manifestation. The skin is often soft or velvety and may be mildly hyperextensible. Subluxations and dislocations are common; they may occur spontaneously or with minimal trauma and can be acutely painful. Degenerative joint disease is common. Chronic pain, distinct from that associated with acute dislocations or advanced osteoarthritis, is a serious complication of the condition and can be both physically and psychologically disabling. Easy bruising is common, but atrophic scarring is more characteristic of the classic type of EDS. Joint hypermobility is the primary clinical manifestation. Skin abnormalities, such as variable skin hyperextensibility and smooth velvety skin, are found; but the presence of atrophic scars in individuals with joint hypermobility suggests the diagnosis of classic EDS.

The diagnosis of EDS, hypermobility type is based entirely on clinical evaluation andfamily history. In most individuals with EDS, hypermobility type, the gene in whichmutation is causative is unknown and unmapped [Malfait et al 2006a]. Haploinsufficiency of TNXB (the gene encoding tenascin X) and heterozygosity for missense mutations in TNXB have been associated with EDS, hypermobility type in a small subset of affected individuals (see Tenascin X deficiency) [Zweers et al 2003,Zweers et al 2005]. A single occurrence of a COL3A1 mutation in a family thought to have EDS, hypermobility type has been reported. Inheritance is autosomal dominant.

Tenascin X deficiency. Homozygous pathogenic variants in TNXB have been identified in individuals with an autosomal recessive EDS phenotype characterized by mild joint hypermobility, skin hyperextensibility, and easy bruising but without atrophic scarring [Schalkwijk et al 2001, Lindor & Bristow 2005]. Heterozygotes for the same pathogenic variant, especially females, appear to have an EDS hypermobility phenotype.

Familial joint hypermobility syndrome, and other syndromes in which hypermobility is found, share hypermobility of the joints with classic EDS; but the absence of skin hyperextensibility and atrophic scarring excludes the diagnosis of classic EDS.

Ehlers-Danlos syndrome, vascular type (EDS type IV) is characterized by thin, translucent skin; easy bruising; characteristic facial appearance; and arterial, intestinal, and/or uterine fragility. Affected individuals are at risk for arterial rupture, aneurysm, and/or dissection; gastrointestinal perforation or rupture; and uterine rupture during pregnancy. One fourth of individuals with EDS, vascular type experience a significant medical problem by age 20 years and more than 80% by age 40 years. The median age of death is 48 years.

The diagnosis of EDS, vascular type is based on clinical findings and confirmed by biochemical and/or molecular genetic testing. Biochemical studies in affected individuals demonstrate abnormal electrophoretic mobility and abnormal efficiency of secretion of type III procollagen by cultured dermal fibroblasts. Molecular genetic testing is used to identify pathogenic variants in COL3A1. Inheritance is autosomal dominant.

Ehlers-Danlos syndrome, progeroid form is a rare autosomal recessive disorder characterized by progeroid appearance with wrinkled facies, curly and fine hair, scanty eyebrows and eyelashes, and periodontitis, in addition to typical signs of EDS. It is caused by homozygous pathogenic variants in B4GALT7, the gene encoding beta-1,4-galactosyltransferase 7.

Ehlers-Danlos syndrome, kyphoscoliotic form (previously known as EDS type VI) is a generalized connective tissue disorder characterized by kyphoscoliosis, joint laxity, muscle hypotonia, and, in some individuals, fragility of the ocular globe. Intelligence is normal; life span may be normal, but affected individuals are at risk for rupture of medium-sized arteries and respiratory compromise if kyphoscoliosis is severe.

EDS, kyphoscoliotic form is caused by mutation of PLOD1, resulting in deficient activity of the enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1: lysyl hydroxylase 1). The diagnosis of EDS, kyphoscoliotic form relies on the demonstration of an increased ratio of deoxypyridinoline to pyridinoline crosslinks in urine measured by HPLC, a highly sensitive and specific test. Assay of lysyl hydroxylase enzyme activity in skin fibroblasts and molecular genetic testing of PLOD1 are possible. Inheritance isautosomal recessive.

Ehlers-Danlos syndrome, arthrochalasia type (previously called type VIIA & B) is distinguished by congenital bilateral hip dislocation and severe joint hypermobility. Tissue fragility (including atrophic scars) and skin hyperextensibility are usually present; severity ranges from mild to severe. It is caused by mutation of COL1A1 or COL1A2leading to the deletion of exon 6 of the mRNA coding for the α1 chain (EDS VIIA) or the α2 chain (EDS VIIB) of type I collagen, respectively. Inheritance is autosomal dominant.

Ehlers-Danlos syndrome, dermatosparaxis type (previously called EDS type VIIC) is characterized by extreme skin fragility, laxity, and a sagging, redundant appearance. Other distinct features are delayed closure of the fontanels, characteristic facies, edema of the eyelids, blue sclerae, umbilical hernia, short fingers, and short stature. The disorder is caused by deficient activity of procollagen-N-proteinase, the enzyme that excises the N-terminal propeptide in procollagen types I, II, and III [Malfait et al 2005]. Inheritance is autosomal recessive.

Ehlers-Danlos syndrome, cardiac valvular form is characterized by joint hypermobility, skin hyperextensibility, and sometimes atrophic scarring, as well as cardiac valvular defects. Total absence of the proα2(I) chains of type I collagen as a result of homozygous or compound heterozygous pathogenic variants in COL1A2 is causative [Schwarze et al 2004, Malfait et al 2006b]. Inheritance is autosomal recessive.

Classic-like EDS with propensity for arterial rupture. One arginine-to-cysteine (Arg-to-Cys) substitution in proα1(I) chain of type I collagen (p.Arg134Cys) has been identified in a series of individuals with a condition reminiscent of classic EDS that manifests as skin hyperextensibility, easy bruising, atrophic scarring, and joint hypermobility as well as a propensity for arterial rupture in adulthood [Nuytinck et al 2000, Malfait et al 2007]. Two other proα1(I) R-to-C substitutions (p.Arg396Cys and p.Arg915Cys) were also associated with rupture of medium-sized arteries, but affectedindividuals did not have EDS-like skin features [Malfait et al 2007]. Furthermore, a pro1(I)-p.Arg888Cys substitution was reported in a family presenting an EDS/osteogenesis imperfecta overlap phenotype [Cabral et al 2007], and a proα1(I)-p.Arg836Cys substitution was shown to be associated with autosomal dominant Caffey disease[Gensure et al 2005].

Ehlers-Danlos syndrome and periventricular nodular heterotopia. Pathogenic variants in FLNA have been identified in a limited number of individuals with periventricular nodular heterotopia (a neuronal migration disorder characterized by seizures and conglomerates of neural cells around the lateral ventricles of the brain) and features of EDS [Gómez-Garre et al 2006]. See X-Linked Periventricular Heterotopia.

Ehlers-Danlos syndrome spondylocheirodyplastic form is characterized by hyperextensible thin skin, easy bruising, hypermobility of the small joints with a tendency to contractures, protuberant eyes with bluish sclerae, hands with finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. Skeletal surveys show platyspondyly with moderate short stature, osteopenia, and widened metaphyses. Mutation of SLC39A13, encoding the membrane-bound zinc transporter SLC39A13, is causative [Giunta et al 2008]. Inheritance is autosomal recessive.

The RIN2-syndrome (also known as MACS syndrome) is characterized by severe progressive scoliosis, progressive facial coarsening, gingival hypertrophy, sparse hair, and skin and joint hyperlaxity. It is caused by mutation of RIN2, the gene encoding the Ras and Rab interactor 2 that acts as a guanine nucleotide exchange factor (GEF) for the small GTPase Rab5, which is involved in early endocytosis [Basel-Vanagaite et al 2009,Syx et al 2010]. Inheritance is autosomal recessive.

Ehlers-Danlos syndrome musculocontractural type is characterized by craniofacial dysmorphism, hyperextensible thin skin, atrophic scarring, easy bruising, small joint hypermobility, hands with finely wrinkled palms and tapered fingers, congenitalcontractures of distal joints, scoliosis, progressive muscle hypotonia, and variable gastrointestinal and genitourinary involvement. The condition is caused by mutation ofCHST14, encoding dermatan 4 sulfotransferase-1, which is involved in the biosynthesis of dermatan sulfate. Inheritance is autosomal recessive [Malfait et al 2010, Miyake et al 2010].

Classic EDS shows limited overlap with other connective tissue disorders, including variants of the following; these disorders are differentiated by other distinctive clinical features:
Marfan syndrome, caused by mutation of FBN1, has a broad continuum of clinical manifestations involving the ocular, skeletal, and cardiovascular systems. Lens dislocation, seen in approximately 60%, is a hallmark feature. Myopia, retinal detachment, glaucoma, and early cataract formation are seen. Bone overgrowth leads to long extremities, pectus deformity (excavatum or carinatum), and joint laxity; scoliosis is common. Cardiovascular manifestations include dilatation of the aorta, a predisposition for aortic tear and rupture, mitral valve prolapse with or without regurgitation, tricuspid valve prolapse, and enlargement of the proximal pulmonary artery. Marfan syndrome is a clinical diagnosis based on family history and the observation of characteristic findings in multiple organ systems. Diagnostic criteria have been established. Inheritance is autosomal dominant.
Occipital horn syndrome (OHS) (see ATP7A-Related Copper Transport Disorders) is characterized by "occipital horns," distinctive wedge-shaped calcifications at the sites of attachment of the trapezius muscle and the sternocleidomastoid muscle to the occipital bone. Occipital horns may be clinically palpable or observed on skull radiographs. Individuals with OHS also have lax skin and joints, bladder diverticula, inguinal hernias, and vascular tortuosity. There is no particular ease of bruising or fragility of the skin. Serum copper concentration and serum ceruloplasmin concentration are low. Mutation ofATP7A is causative. Inheritance is X-linked.
Hyperextensible skin should also be distinguished from that observed in the cutis laxa syndromes and in De Barsy syndrome, in which the redundant skin hangs in loose folds and only returns very slowly to its former position. In these syndromes, the skin is not fragile and wound healing is normal. The cutis laxa syndromes result from the loss or fragmentation of the elastic fiber network. They are variably associated with pulmonary, cardiac, arterial, and gastrointestinal abnormalities. Cutis laxa syndromes comprise autosomal dominant, autosomal recessive, and X-linked forms. The autosomal dominant form is caused bymutation of ELN, encoding elastin. Autosomal recessive forms of cutis laxa are associated with mutation of the genes encoding fibulin 4 and fibulin 5 (FBLN4and FBLN5), and more recently also with mutation of ATP6V0A2 and PYCR1.
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Management

For a detailed review of complications and management, see Wenstrup & Hoechstetter [2004].

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with Ehlers-Danlos syndrome (EDS), classic type, the following evaluations are recommended:
Clinical examination of the skin with assessment of skin hyperextensibility, atrophic scars and bruises, and other manifestations of classic EDS
Evaluation of joint mobility with use of the Beighton score
Evaluation for hypotonia and motor development in infants and children
A baseline echocardiogram with aortic diameter measurement for individuals under age ten years
Evaluation of clotting factors if severe easy bruising is present

Treatment of Manifestations

In children with hypotonia and delayed motor development, a physiotherapeutic program is important.

Non-weight-bearing muscular exercise, such as swimming, is useful to promote muscular development and coordination.

Individuals with muscle hypotonia and joint instability with chronic pain may have to adjust lifestyle and professional choices accordingly. Emotional support and behavioral and psychological therapy may help in developing acceptance and coping skills.

Dermal wounds should be closed without tension, preferably in two layers. Deep stitches should be applied generously. Cutaneous stitches should be left in place twice as long as usual and additional fixation of adjacent skin with adhesive tape can help prevent stretching of the scar.

For recommendations on treatment of joint laxity and dislocations, see EDS, Hypermobility Type. (Note: Surgical stabilization of joints may lead to disappointing, or only temporary, improvement.)

Anti-inflammatory drugs may help with joint pain.

Long-term chronic pain may result in the need for mental health services.

Cardiovascular problems should be treated in a standard manner.

Prevention of Primary Manifestations

Very young children with pronounced skin fragility can wear protective pads or bandages over the forehead, knees, and shins in order to avoid skin tears. Older children who are active can wear soccer pads or ski stockings with shin padding during activities.

For recommendations on prevention of primary manifestations of joint laxity and dislocations, see EDS, Hypermobility Type: Management, Prevention of Primary Manifestations.

Ascorbic acid (vitamin C) may reduce easy bruising but has no effect on the primary findings of skin hyperextensibility, atrophic scarring, and joint hypermobility. In general, a dose of two grams per day is recommended for adults, with proportionally reduced doses for children; however, there is no limitation.

Prevention of Secondary Complications

For recommendations on prevention of secondary manifestations of joint laxity and dislocations, see EDS, Hypermobility Type: Management, Prevention of Secondary Complications.

Surveillance

If no abnormalities are found on echocardiogram in an adult, a follow-up echocardiogram is not necessary. (Because longitudinal data on progression of aortic dilation are not available, specific recommendations for follow-up in individuals with a normal aortic diameter are not available.)

Yearly echocardiogram is warranted if an abnormality such as aortic dilatation or mitral valve prolapse is present.

Agents/Circumstances to Avoid

The following should be avoided:
Sports with heavy joint strain (contact sports, fighting sports, football, running)
Acetylsalicylate (aspirin)

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes

Pregnancy Management

Because of the increased risk of skin lacerations, postpartum hemorrhages, and prolapse of the uterus and/or bladder, monitoring of women throughout pregnancy and in the postpartum period is recommended.

Ascorbic acid (vitamin C) may reduce easy bruising (see Prevention of Primary Manifestations). In general, a dose of two grams per day is recommended for adults; however, no strict guidelines exist regarding recommended dose during the third trimester of pregnancy.

Monitoring of pregnant women for preterm labor is warranted during the third trimester when the risk of premature rupture of the membranes is increased.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
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Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Ehlers-Danlos syndrome (EDS), classic type is inherited in an autosomal dominantmanner.

Risk to Family Members

Parents of a proband
It is estimated that approximately 50% of affected individuals have inherited thedisease-causing mutation from an affected parent and approximately 50% of affected individuals have a de novo disease-causing mutation.
The parents of a proband with apparent de novo mutation should be evaluated by physical examination of the skin with special attention to delayed wound healing, easy bruising, joint hypermobility or recurrent dislocations, and chronic articular pain. If a disease-causing mutation has been identified in the proband, molecular genetic testing is performed in the parents.

Note: Although approximately 50% of individuals diagnosed with classic EDS have anaffected parent, the family history may appear to be negative because of failure to recognize the disorder in family members.

Sibs of a proband
The risk to sibs of the proband depends on the genetic status of the proband's parents.
If a parent of the proband is affected, the risk to the sibs is 50%.
When the parents are clinically unaffected, the risk to the sibs of a probandappears to be low.
Although no instances of germline mosaicism have been reported, it remains a theoretical possibility in a minority of cases.

Offspring of a proband. Each child of an individual with classic EDS has a 50% chance of inheriting the mutation.

Other family members of a proband. The risk to other family members depends on the status of the proband's parents. If a parent is affected or has a disease-causing mutation, his/her family members are at risk.

Related Genetic Counseling Issues

Prediction of phenotype. Because of intrafamilial clinical variability, it is not possible to predict the phenotype in family members who have inherited a disease-causing mutation.

Considerations in families with apparent de novo mutation. When neither parent of aproband with an autosomal dominant condition has the pathogenic variant or clinical evidence of the disorder, it is likely that mutation occurred de novo in the proband; however, the frequency of parental mosaicism is unknown. Additional explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.

Family planning
The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the pathogenic variant has been identified in an affected family member, prenatal diagnosis for pregnancies at increased risk may be available from a clinical laboratory that offers either testing for the gene of interest or custom prenatal testing.

Requests for prenatal testing for conditions which (like classic EDS) do not affect intellect or life span are not common. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the pathogenic variant has been identified.
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Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.
Association Francaise des Syndrome d'Ehlers Danlos
34 rue Léon Joulin
Turns 37 000
France
Email: contact@afsed.com
www.afsed.com
Ehlers-Danlos National Foundation
1760 Old Meadow Road
Suite 500
McLean VA 22102
Phone: 703-506-2892
Email: ednfstaff@ednf.org
www.ednf.org
Ehlers-Danlos Support Group
PO Box 337
Aldershot Surrey GU12 6WZ
United Kingdom
Phone: 01252 690940
Email: director@ehlers-danlos.org
www.ehlers-danlos.org
National Library of Medicine Genetics Home Reference
Ehlers-Danlos syndrome
Medline Plus
Ehler-Danlos Syndrome
National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)
Phone: 800-334-8571 ext 24640
Email: gentac-registry@rti.org
GenTAC
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Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.


Ehlers-Danlos Syndrome, Classic Type: Genes and Databases

Gene SymbolChromosomal LocusProtein NameLocus SpecificHGMD
COL5A1 9q34​.3 Collagen alpha-1(V) chain Ehlers-Danlos Syndrome Variant Database (COL5A1) COL5A1
COL5A2 2q32​.2 Collagen alpha-2(V) chain Ehlers-Danlos Syndrome Variant Database (COL5A2) COL5A2



Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.


OMIM Entries for Ehlers-Danlos Syndrome, Classic Type (View All in OMIM)

120190 COLLAGEN, TYPE V, ALPHA-2; COL5A2
120215 COLLAGEN, TYPE V, ALPHA-1; COL5A1
130000 EHLERS-DANLOS SYNDROME, CLASSIC TYPE
130010 none found


COL5A1

Gene structure. The COL5A1 cDNA comprises 66 exons distributed over more than 150 kb of genomic DNA. For a detailed summary of gene and protein information, see Table A, Gene Symbol.

Pathogenic allelic variants. Several types of mutations have been identified in bothCOL5A1 and COL5A2:
The most common types of molecular defect lead to haploinsufficiency forCOL5A1 mRNA. In approximately 40% of individuals with classic EDS, nonsense or frameshift mutations are responsible for a non-functional COL5A1allele [Schwarze et al 2000, Wenstrup et al 2000, Schwarze et al 2001, Malfait et al 2005]. Nonsense, frameshift, or splice-site mutations that introduce a premature termination codon are usually responsible for this non-functionalCOL5A1 allele. A variety of mechanisms lead to nonsense-mediated decay of themutation-bearing mRNA or to failure of the chains to associate. The predicted consequence is synthesis of approximately half the amount of normal type V collagen.
Structural mutations in COL5A1, which exert a dominant-negative effect, have been demonstrated in approximately ten to 15 individuals with classic EDS. In a small proportion of individuals, a mutation affects the structural integrity of type V collagen, resulting in the production of a functionally defective type V collagen protein (dominant-negative mutation). These structural mutations are most commonly splice-site mutations that result in exon skipping [Burrows et al 1998,Malfait et al 2005] and a few point mutations that result in the substitution for glycine in the triple-helical region of the collagen molecule [Giunta & Steinmann 2000, Malfait et al 2005]. A unique point mutation in COL5A1 that changes a highly conserved cysteine residue to a serine in the C-terminal propeptide of the α1(V) collagen chain has also been identified (p.Cys1639Ser) (NM_000093.3:c.4916G>C). In contrast to other disorders characterized by mutation of the fibrillar collagen genes, remarkably few pathogenic variants resulting from the substitution of a glycine by a bulkier amino acid have been found.
A p.Gly530Ser (NM_000093.3: c.1588G>A) substitution in the amino-terminal propeptide of the α1(V) chain may be disease-modifying when present in the heterozygous state and disease-causing in the homozygous state [Giunta & Steinmann 2000, Giunta et al 2002].

Normal gene product. Collagen α1 (V) chain (type V collagen chains). Type V collagen is a quantitatively minor fibrillar collagen that is widely distributed in a variety of tissues. It is present mainly as [α1(V)]2 α2(V) heterotrimers in skin, bone, and tendon. It forms heterotypic fibrils with type I collagen and regulates the diameter of those fibrils, presumably through its very large amino-terminal propeptide. Recent data indicate that type V collagen controls collagen fibril assembly in several tissues [Wenstrup et al 2004].

Abnormal gene product. Missense mutations in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity; i.e., the mutant forms can interfere with the utilization of the normal protein derived from the normal allele. Diminished amounts, caused by premature termination of codons in COL5A1 or mRNA product, may alter normal collagen fibrillogenesis.

COL5A2

Gene structure. The COL5A2 cDNA comprises 51 exons distributed over 67 kb. For a detailed summary of gene and protein information, see Table A, Gene Symbol.

Pathogenic allelic variants. Structural mutations in COL5A2 have been demonstrated in few individuals with classic EDS. These structural mutations are most commonly splice-site mutations that result in exon skipping [Michalickova et al 1998, Malfait et al 2005] and one point mutation that results in a substitution for glycine in the triple helical region of the collagen molecule [Richards et al 1998].

Normal gene product. Collagen α2(V) chains (type V collagen chains). Type V collagen is a quantitatively minor fibrillar collagen that is widely distributed in a variety of tissues. It is present mainly as [α1(V)]2, α2(V) heterotrimers in skin, bone, and tendon. It forms heterotypic fibrils with type I collagen and regulates the diameter of those fibrils, presumably through its very large amino-terminal propeptide.

Abnormal gene product. Missense mutations in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity; that is, the mutant forms can interfere with the utilization of the normal protein derived from the normal allele.
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References

Published Guidelines/Consensus Statements
Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers- Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Available online. 1998. Accessed 4-3-15. [PubMed]

Literature Cited
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