Ehlers-Danlos Syndrome (EDS)

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder with six predominant types: Classical (type I and II), Hypermobility (type III), Vascular/VEDS (type IV), Kyphoscoliosis (type VI), Arthrochalasia (type VII-A and VII-B) and Dermatosparaxis (type VII-C).  Related syndromes known to be much less common include Type V, Type VIII, Type X, and Deficient Ehlers-Danlos syndrome.  EDS is caused by a defect in the genes that tell your body how to make collagen, COL5A and COL3A.  Collagen is the most common protein found in connective tissues, the tissues that support, connect or separate the other tissues or organs.  The defective collagen types found in these patients cause weakened connective tissue. 

All types of EDS cause changes to the skin, ligaments, tendons, bone, fascia and eyes.  Hypermobility of the joints of the bones in the middle ear can cause problems with sound conduction through the middle ear.  This can lead to conductive hearing loss, usually moderate but occasionally severe, and treatable with hearing aids.  This type of hearing loss can be easily confused with otosclerosis, the treatment for which involves surgery.  If this surgery is performed in EDS patients, it can easily result in total loss of hearing and disruption of balance. 

POTS commonly co-occurs with EDS.  This is thought to be due to the weakened connective tissue in blood vessels, which cause veins to become misshapen in the presence of regular blood pressure.  This results in excessive blood pooling in the patient’s lower half when they stand.

The different types of EDS do not represent differences in severity.  They are unique disorders that are inherited and remain the same within a family. 

Hypermobility type (Type III) is the most commonly identified subset in clinical practice.  Both large and small joints are hypermobile in this group.  Recurrent dislocations and subluxations (partial dislocations) are evident in these people.  Some joints, like the shoulder and temperomandibular (TMJ) joint dislocate often.  Skin is usually smooth, velvety, and may or may not be unusually elastic.  People with this type bruise easily.  The most prominent manifestation of this type is chronic pain, especially if it is seemingly disproportionate to the injury.  This may be due to muscle spasm or arthritis.  Neuropathy is also very common in these patients.  There are no specific genetic mutations associated with this type.  Type III is inherited in an autosomal dominant pattern.

Classical types (I and II) show very stretchy skin, joint hypermobility and atrophic scarring, which looks like pits in the skin.  This is caused by the loss of the tissue under the scar.  (It is the type of scarring caused by chicken pox.)  The skin is smooth, velvety and easily damaged.  Their tissues are fragile, resulting in herniation or prolapse.  Hernias often occur after an operation.  Scars are often found on the knees, elbows, forehead and chin.  Sprains, dislocations, subluxations and flat feet are often found.  Low muscle tone and delayed gross motor development occur in some patients.  90% of people with classical types have a genetic defect in collagen type V.

Vascular type (Type IV) is the most serious manifestation of EDS as it can lead to arterial or organ rupture.  Skin is usually very thin with veins easily visible through the chest and abdomen.  These individuals tend to have large eyes, thin nose, thin scalp hair, short stature and lobeless ears.  Minor injury can cause extensive bruising.  Arterial and intestinal rupture often occur in this type of EDS.  Uterine fragility is also a common finding.  Sudden arterial rupture most frequently happens between the ages of 20 and 40, but sometimes happens in children.  Midsize arteries are usually affected.  This is the most frequent cause of sudden death in EDS patients.  Sudden abdominal or flank pain, either focused or throughout, can be indicative of arterial or intestinal rupture.  Life expectancy for patients with this type is shortened, most patients living into their 40’s.  Pregnancies may cause uterine rupture during the pregnancy, as well as arterial bleeding before or after delivery.  Joint hypermobility is generally found only in the fingers and toes.  Tendon and muscle rupture sometimes occurs.  Clubfoot is sometimes seen at birth.  Varicose veins, “old looking” skin, collapsed lungs, gum recession and poor wound healing after surgery are also sometimes found.  Type IV is caused by a defect in gene COL3A1.  It is inherited in an autosomal dominant pattern.

Kyphoscoliosis type (type VI) has a specific type of unusual curvature of the spine.  Severely weak muscle tone and joint hypermobility are obvious at birth.  People with this type are frequently wheelchair bound after the second or third decade of life.  They are very susceptible to eye damage.  They also show atrophic scars and easy bruising.  Spontaneous arterial rupture sometimes occurs.  They sometimes have Marfan-like features, very small cornea and diminished bone tissue.  This type is due to a deficiency in PLOD, a collagen-modifying enzyme.  It is inherited in an autosomal recessive manner.

Artherochalasia (type VII-A and VII-B) is marked by severe hypermobility of joints.  Hip dislocation after birth has been found in all patients with this type.  They often have frequent subluxation of large joints, very stretchy skin, easy bruising, fragile tissues, atrophic scars, low muscle tone, unusual curvature of the spine and mild bone loss.  It is caused by mutations affecting collagen type I.  It is inherited in an autosomal dominant manner.

Dermatosparaxis (type VII-C) patients have very fragile skin and frequent, severe bruising.  However, their wounds heal properly and their scars are not atrophic.  The skin is doughy and frequently sags, especially on the face, giving the appearance of premature aging.  Large hernias are often present.  It is caused by mutation of a pro-collagen molecule.  It is inherited in an autosomal recessive manner.

Ehlers-Danlos syndrome is commonly found in the presence of mast cell disease.  Furthermore, the co-occurrence of EDS, POTS and mast cell disease has been found to be present more often than would be likely by chance.  The relationship between the three conditions, especially EDS/POTS/MCAS is the subject of recent research.