What is Ehlers-Danlos Syndrome?

Ehlers-Danlos Syndrome Hypermobility Type: An Autosomal Dominant Genetic Disorder That Has Numerous Health Consequences That Is Poorly Understood by the Medical Community

EDS is a genetic disorder that affects the collagen elastin matrix throughout the body.  The collagen elastin matrix provides scaffolding and structural integrity for the body including organs, blood vessels, ligaments, tendons and integuments. At this time there have been 13 different forms of EDS described.  Most forms are relatively rare, and many have known genetic defects that can be tested for including among others mutations in their collagen genes (COL).

For individuals with classic EDS, the most frequent genetic mutations are found in COL5A1 and COL5A2.  These mutations cause the skin to be extremely elastic and fragile, so that it easily bruises, and the patients often experience delayed wound healing that can be very problematic, especially after having surgery.  If a surgical wound is not carefully stitched back together from the inside to the outer part of the surgical wound the defect in the collagen matrix will not be able to mend together and as a result the wound can open a few days later. This is known as wound dehiscence.  It takes a lot of effort once this happens to reestablish wound healing that can take weeks to months to resolve.  These patients also have increased elasticity of their ligaments resulting in significant joint hypermobility that can result in joint dislocations.  This form of EDS also causes soft tissue calcifications over pressure points like elbows and knees.

Vascular EDS has many of the skin conditions associated with classic EDS and is particularly concerning because it also causes fragile blood vessels and organs that can easily rupture.  A strong family history of cardiac events and aneurysms bursting can be helpful.

It is important for young women of childbearing age to know that they have Ehlers-Danlos syndrome hypermobility type because if they become pregnant their pregnancy is high risk.  The major complications include pre-labor rupture of membranes, wide swings in blood pressure; blood pressure can precipitously drop during anesthesia for a C-section, increased bleeding causing increased risk of antepartum and postpartum hemorrhaging due to capillary fragility, and delayed wound healing from the birthing process.  Often the birthing process happens very quickly due to laxity of the pelvic structures and there can be a malposition of the fetus as well as preterm birth caused by cervical incompetence.  Women postpartum can experience joint subluxations; joints moving out of place including hip dislocation.  They also can endure widespread joint pain after birth.

Examples of Hypermobility

Hypermobile EDS (hEDS) is a autosomal dominant genetic disorder and therefore offspring of one parent having hEDS have a 50% chance of acquiring it whereas if both parents have it the offspring have a 75% chance.  Since it is a genetic disorder, you are born with it and it will be with you for your entire life.  It has been suggested that you cannot make a diagnosis of hEDS in a child until they are 5 years of age.  This concept defies logic.  It is important to recognize as soon as possible whether an infant and young child under the age of 5 years has this genetic disorder.  For infants, this genetic disorder can cause a variety of physical signs and medical conditions.

I would advise my hEDS patients who were planning to have a family to be not only aware that the pregnancy is high risk but that the infant can present with a multitude of medical symptoms and conditions that often need recognition and attention.  Parent(s) who have an infant with hEDS would tell me that when they would pick up their infant, they could feel the joints click.  This was especially common for shoulders, hips and ribs. Infants are able to easily get out of swaddling due to their joint hypermobility.

Parents often will notice that the skin can appear mottled which are irregular patches of discoloration to form a net-like or marble-like pattern across the skin especially abdomen and chest.  This can appear and then disappear in a few seconds or sometimes takes minutes.  The pattern contains areas of red, blue/purple and white that can be mistaken as a bruise.  Infants with darker skin tones often have a pattern of dark brown.  The quick disappearance of this skin discoloration however indicates that it is not a bruise.

Infants with hEDS are prone to spitting up feedings and even having projectile vomiting.  This is often misdiagnosed as gastroesophageal reflux or caused by an allergy to either mom’s milk or the formula.  Infants are often placed on medication to reduce gastric acid production.  When this intervention does not help, often its concluded that the infant has an allergy to their feeding and are placed on various infant formulas and different forms of milk including goat and sheep milk to overcome this feeding problem.

In some cases when the infant is not obtaining an adequate amount of nutrition and calories, this can lead to weight loss or poor weight gain. Many of these infants with hEDS are suffering from gastroparesis.  I informed parents that to overcome symptoms of gastroparesis decreasing the size of the feeding and increasing the number of feedings so that the same number of calories are being ingested can often overcome this medical issue.  Infants and children with hEDS often have capillary fragility resulting in easy bruising.  It is important to recognize this association.

In some cases, parents will bring their infant to a pediatrician because of concern about the bruises.  Often either the pediatrician or a consulting hematologist will conduct an evaluation to determine if the infant or child has an acquired or genetic disorder that causes a bleeding disorder.  These disorders are rare and usually the evaluation provides no insight into the easy bruising.  A concerned parent bringing in the child several times with unexplained bruises can sometimes lead to the misdiagnosis of being caused by nonaccidental trauma i.e. child abuse.  I also educate parents that if their child bruises easily that they should be concerned that any mild trauma to the head could also cause brain bleeding (subdural hematoma) which if not recognized can lead to neurological disorder such as paraplegia or even death.

I educate parents that children with hEDS as they begin to crawl, and walk are more prone to sustaining a head injury.  I recommend either a soft or hard helmet to help lessen the trauma to the head if the child inadvertently sustains a head injury.  Infants with hEDS often have dyspraxia causing developmental coordination disorder resulting in hypotonia, non-specific developmental delay in gross and fine motor skills and increased laxity of the joints.  This can cause delay in the child succeeding in crawling.  As they begin to crawl and lift their body with their arms they often will fall forward to the ground. I recommend that they should begin crawling on soft carpet to help mitigate any trauma from falling forward.

I have found that infants with hEDS, as they begin to walk, often will walk on their tippy toes.  This is in part due to laxity of the ligaments in the ankles causing instability.  By hyperextending the feet to the floor, the ligaments are hyperextended to the point where they can no longer stretch, thereby stabilizing the ankles and permitting the child to walk.  I recommend parents to protect clicking loose joints with an Ace bandage. It is well-documented that children and adults with hEDS are at much higher risk for fracture.  Parents and pediatricians need to be aware of this association.

An infant with hEDS presenting with an upper respiratory tract infection and found on x-ray to have rib fractures can lead to a misdiagnosis of nonaccidental trauma caused by child abuse.  I have seen numerous infants with many fractures in various stages of healing who have at least one parent with hEDS and who have many of the physical signs and medical conditions consistent with them having the bone fragility disorder, hEDS. 

Children with hEDS are also more prone to easy fatigue and have a difficult time focusing and appear fidgety.  These children often require more rest periods and the inability to focus is often misdiagnosed as attention deficit disorder when it is more likely caused by dysautonomia that is often present in hEDS patients.  Some children and especially teenagers who have hEDS with multiple medical problems, including feeling lightheaded when standing up quickly, unable to tolerate a normal sized meal, flushing easily without provocation, bruise easily, complain of migratory pains in their muscles and joints and are unable to sit still and focus, are often written off by the pediatrician as due to doctor seeking, drug seeking or depression.  Many are sent to a psychologist or psychiatric facility for further evaluation.

Concerned parents who desperately try to find medical solutions for their child’s medical problems can be falsely accused of Munchhausen by proxy.  This is especially true when parents are seeking medical assistance for their child and she a multitude of medical specialists. What I found to be very helpful when I saw these children is to make the parents aware that their child is not crazy or depressed but rather these many different disparate medical conditions are associated with one cause, and autosomal dominant genetic disorder of the collagen elastin matrix i.e. scaffolding of the entire body, hEDS.  Just knowing that there is an explanation for these many medical conditions often gives great relief to both the child and the parents who now have a more credible explanation for their child’s medical conditions.

From my experience of seeing more than 4000 children and adults with hEDS over the past 40 years I have found that most adults with this genetic disorder were clueless that they had hEDS.  Like infants and children, adults with hEDS can bruise easily, suffer from mast cell hypersensitivity, postural orthostatic tachycardia syndrome, experience poor wound healing, feel uncomfortable eating normal sized meal, feel their joints click including their temporomandibular joints in their jaw and experience acute and chronic migratory pains in their muscles and joints.  They also do not appreciate that they are at ten times higher risk of having a fragility fracture with an amount of trauma that would not cause a fracture in an adult matched for sex and age.

A good example was that I received a frantic phone call from my orthopedic surgeon colleague asking my advice about his neighbor’s teenager who was a senior in high school and sustained intense pain when he put on his backpack heavily laden with books.  An x-ray revealed that he suffered a compression fracture in his thoracic spine at the level of T4. What was very concerning to his parents, which is why they contacted their orthopedic surgeon neighbor, was that an x-ray of the spine identified multiple healed fractures.  I saw the teenager and his mother in my clinic and informed both that they had hEDS and that they were at a higher risk for sustaining fragility fractures caused by an amount of trauma times that would not cause a fracture in a child or adult matched for sex and age.  I advised the teen to be more cautious about how much weight he places in his backpack and that any lifting should always be with his legs and never with his back to minimize further spinal fractures. I am listing below the large number of medical consequences associated with this genetic disorder that are often misunderstood or misdiagnosed by healthcare professionals.

Associated Medical Consequences & Symptoms

I am listing below the large number of medical consequences associated with this genetic disorder that are often misunderstood or misdiagnosed by healthcare professionals.

1. Chronic and acute pain syndrome.  This is one of the most common complaints I would receive from a patient seeing me in consultation for their bone pain.  Migratory pains in muscles and joints, that are often misdiagnosed as fibromyalgia, depression, doctor-seeking or drug-seeking, is associated with hEDS.  The cause is not fully understood but thought in part due to dysautonomia and some unknown neuropathic etiology.  hEDS patients are also more prone to having complex regional pain syndrome due to a joint injury or the underlying fragility of nerve connective tissue.
2. Partial or complete joint subluxations due to laxity of the ligaments.  Multiple insults including partial and complete subluxations of  the joints can cause joint pain and discomfort, compromise joint mobility and increased risk for early onset osteoarthritis.
3. Fatigue  Complaints of fatigue seen in children and adolescents is also common in adults especially females.  It can be debilitating and cause neurocognitive dysfunction.  It has also been associated with sleep irregularity resulting in nonrestorative sleep thereby exacerbating fatigue, headaches and other psychological issues.
4. Postural Orthostatic Tachycardia Syndrome (POTS).  Patients often complain of feeling lightheaded when standing up quickly with their heart beating fast in their chest.  Many are advised by their health care professional that they are simply dehydrated and drinking more water will relieve them of their problem. It does not.
5. Gastroparesis and other GI symptoms.  Many patients complain that they feel uncomfortable when eating a normal or large sized meal.  This is due to alterations in the motility of the gastrointestinal tract.  Many of these patients become morbidly obese which seems counterintuitive until it is appreciated that these patients who are eating a small meal to control their GI symptoms are not satisfying their satiety center.  As a result, the patient continues to constantly snack throughout the day markedly increasing the calorie intake above and beyond what would have occurred if they were able to consume a normal calorie meal.  These patients often complain of chronic diarrhea or constipation and are misdiagnosed as having irritable bowel syndrome.  Abdominal hernias are often present in about 20% of patients as well as rectal prolapse documented to be about 10% in female patients.
6. Mast cell hypersensitivity.  Most of my pediatric and adult patients often complained of flushing easily without provocation and sweating profusely.  This is due to the release of histamine often without a known cause.  The unprovoked release of histamine is due to mast cell activation caused by increased numbers of mast cells or factors such as histamine tryptase that prime mast cells to release histamine.  This results in vasodilation of the blood vessels causing the red appearance usually in the face making the person appear to be embarrassed, profuse sweating and in some instances an itching sensation, GI symptoms including diarrhea, bloating and cramping. A decrease in blood pressure can also occur.
7. Poor wound healing.  It is important to recognize that hEDS causes a defect in the collagen elastin matrix structure that causes delayed wound healing as well as poor wound healing.  I have had several of my hEDS patients who have undergone abdominal surgery develop wound dehiscence i.e. a surgically closed incision inexplicably opens.  This is due to failure of proper wound healing caused by the defective collagen elastin matrix. Surgeons need to be aware that if their patient has hEDS that additional measures need to be taken to properly close the incision from the inside out to reduce risk for this surgical complication. I was consulted by a young woman who underwent what was thought to be a minor surgical procedure on her foot to correct a misalignment of one of the joints in her foot. Two weeks later the surgical wound opened. It took more than 6 months of careful wound healing intervention and careful surgical closure for it to heal.  Patients with hEDS often develop thin hypotrophic scars over their healed wounds.  This is caused by abnormal response to skin injury or wound healing because of the altered collagen elastin matrix.
8. Psychological/psychiatric dysfunction.  A child or adult with a multitude of medical conditions associated with hEDS can weigh heavily on their psyche.  Parents unaware that their child has this genetic disorder often become concerned for the health and well-being of their child because of unexplained medical conditions.  The parents and the child, especially if the child is an adolescent, become frustrated when the pediatrician has no explanation for the myriad of medical symptoms.  As a result, the pediatrician, who is unaware of the many consequences of this genetic disorder, becomes equally frustrated for being unable to find a cause for the symptoms and informs the parents that the child is acting up or seeking attention; none of which is correct.  The child feels isolated and often stops complaining and becomes withdrawn.  Unfortunately, in circumstances where the child is being seen by a pediatrician along with multiple of subspecialists who can find no cause for the myriads of medical symptoms can often lead to a recommendation that the child see a psychologist or a psychiatrist.  In some cases, the psychologist/psychiatrist recommends psychiatric incarceration. I had several adult patients with hEDS who were committed to a psychiatric ward for up to a year. They explained that this experience has caused devastating long-term consequences including PTSD symptoms.  The parents can also be at risk of losing their child because the pediatrician and/or psychiatrist/psychologist conclude that the reason that the parents are bringing their child to see innumerable subspecialists is for their own personal gain.  The parents are then diagnosed with Munchhausen by proxy causing them to lose their suffering child to a foster home or to child protection services.
9. Instability of the cervical, thoracic and lumbosacral spine.  Many of my patients complain of severe intense neuropathic pain often in the shoulders or lower back.  This is often caused by spondylolisthesis (when a vertebral body slips out of place) of a vertebra that presses on nerves exiting the spinal canal.  The laxity of the interspinous ligaments that provide structural support for the vertebral bodies often leads to movement of a vertebral body that then compromises the nerve.  The vertebral movement can also induce inflammation further compromising the affected nerve(s) causing severe unrelenting pain.
10. Osteoporosis.  Children and adults hEDS have been found to have lower bone mineral density.  The skeleton of hEDS patients have a structural defect of a major component of the bone, the collagen elastin matrix, which is mineralized providing strength to the bones.  This underlying structural defect of mineralized bone increases risk of fracture in infants, children and adults.  I have seen female college athletes with stress fractures in her ankles and after careful physical examination concluded that  they had hEDS which I explained to them increases their risk for this type of fragility fracture.
11. Quality of life.  Many of my patients have such intense uncompromising neuropathic pain, fatigue, joint dislocations and other medical conditions that it often causes them to be on permanent disability.  Patients with hEDS have numerous other complaints including sleep disorders, GI symptoms, cardiovascular symptoms, joint pain and migratory aches and pains.  Any one of these can compromise quality of life and having several of them most definitely does.

Conclusion

What I found most rewarding was when I saw a patient in my Bone Health Clinic who was seeing me in consultation for a metabolic bone disease that was associated with low bone mineral density or bone pain is that the patient had hEDS.  Even though the patient was seeing me for a specific endocrine problem I would ask the patient are you double-jointed? Do you feel lightheaded when standing up quickly?  Do you prefer small meals?  Do you bruise easily etc.?  After conducting a further medical history and physical exam I would tell the patient that even though they are seeing me because of a bone problem that there is a much bigger issue i.e. that many of their medical conditions that have been ignored by their physicians have an explanation i.e. caused by a very common autosomal dominant genetic disorder, hypermobile Ehlers-Danlos syndrome.  It is remarkable to see the relief that they instantly experience when they finally realize that they are not crazy and that there is a good explanation for the many medical conditions that they have been suffering with.  In the next installment I will be sharing with you my experiences in treating and mitigating many of the complications associated with this genetic disorder.

Trailer for EDS Documentary “Complicated”

Featuring an interview with Dr. Michael Holick

References

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