Photograph courtesy of Michele L. Hopkins

What is Ehlers-Danlos Syndrome?

According the National Institute of Health, the effects of Ehlers-Danlos Syndrome results from "disrupt(ing) the production or processing of collagen, preventing those molecules from being assembled properly. These defects weaken connective tissues in the skin, bones, and other parts of the body." 

How can someone get Ehlers-danlos Syndrome?

EDS is a genetic disorder, meaning it is commonly passed down through familial DNA. Random gene mutations causing EDS can occur although this is rare. Most types of EDS have an autosomal dominant inheritance pattern, meaning only one copy of the mutation gene(s) is needed to cause the disorder. 

Because it is genetic, EDS cannot be "caught" or "contracted" - it can only be passed down when DNA is inherited. It is also very unlikely that an individual will develop the disease. This means that an individual will be born with Ehlers-Danlos Syndrome, even if they do not exhibit symptoms until later in life. 

What causes Ehlers-danlos Syndrome?

EDS can be caused by mutations to genes including COL5A1, COL5A2, COL1A1, COL3A1, TNXB, PLOD1, COL1A2, FKBP14 and ADAMTS2 - each involving collagen. 

Different mutations to different genes (see table, below) correlate to different types of EDS. This being said, some types, like Hypermobile, have an unknown genetic basis. 

Cures and Treatments

There is no cure for Ehlers-Danlos Syndrome at this point in time. 

There are very little treatments for Ehlers-Danlos Syndrome - it is very important to note that these treatments are only to help the symptoms of the disease, not the disease, itself. These treatments are often very hard to come by, due to the lack of education surrounding Ehlers-Danlos Syndrome.

Types of Ehlers-Danlos

New 2017 classifications

(as of morning of March 15, 2017)

Courtesy of www.ehlers-danlos.com

Courtesy of www.ehlers-danlos.com

Classical-Like EDS

Major criteria are:

  1. Skin hyperextensibility with velvety skin texture and absence of atrophic scarring;
  2. Generalized joint hypermobility (GJH) with or without recurrent dislocations (most often shoulder and ankle); and
  3. Easily bruised skin or spontaneous ecchymoses (discolorations of the skin resulting from bleeding underneath).

There are seven minor criteria. Minimal clinical standards suggesting clEDS are all three major criteria plus a family history compatible with autosomal recessive transmission.

cardiac-Valvular EDS

 Major criteria are:

  1. Severe progressive cardiac-valvular problems (aortic valve, mitral valve);
  2. Skin involvement: skin hyperextensibility, atrophic scars, thin skin, easy bruising; and
  3. Joint hypermobility (generalized or restricted to small joints).

There are four minor criteria. Minimal clinical standards suggesting cvEDS are the first major criterion plus a family history compatible with autosomal recessive transmission, and either one other major criterion or at least two minor criteria.

Vascular EDS

Major criteria are:

  1. Family history of vEDS with documented causative variant in COL3A1;
  2. Arterial rupture at a young age;
  3. Spontaneous sigmoid colon perforation in the absence of known diverticular disease or other bowel pathology;
  4. Uterine rupture during the third trimester in the absence of previous C-section and/or severe peripartum perineum tears; and
  5. Carotid-cavernous sinus fistula (CCSF) formation in the absence of trauma.

There are twelve minor criteria. Minimal clinical standards suggesting vEDS diagnostic studies should be performed are: a family history of the disorder, arterial rupture or dissection in individuals less than 40 years of age; unexplained sigmoid colon rupture: or spontaneous pneumothorax in the presence of other features consistent with vEDS. Testing for vEDS should also be considered in the presence of a combination of the other “minor” criteria.

Hypermobile EDS

The clinical diagnosis of hEDS needs the simultaneous presence of criteria 1 and 2 and 3. This is a complex set of criteria, and there is much more detail than presented in this overview; please see the page for hypermobile EDS.

  1. Generalized joint hypermobility (GJH); and
  2. Two or more of the following features must be present (A & B, A & C, B & C, or A & B & C):

            Feature A—systemic manifestations of a more generalized connective tissue disorder (a total of five out of twelve must be present)

            Feature B—positive family history, with one or more first degree relatives independently meeting the current diagnostic criteria for hEDS

            Feature C—musculoskeletal complications (must have at least one of three); and

  1. All these prerequisites must be met: absence of unusual skin fragility, exclusion of other heritable and acquired connective tissue disorders including autoimmune rheumatologic conditions, and exclusion of alternative diagnoses that may also include joint hypermobility by means of hypotonia and/or connective tissue laxity.

There are a range of conditions commonly found within the hEDS patient population, although direct links cannot be made to be used for diagnostic criteria. Some of these include sleep disturbance, fatigue, postural orthostatic tachycardia, functional gastrointestinal disorders, dysautonomia, anxiety, and depression. These conditions may be more debilitating the joint symptoms; they often impair daily life, and they should be considered and treated.

A diagnosis of hEDS should be assigned only in those who meet all of the criteria, which should help research efforts to discover the underlying genetic cause(s) which, in turn, may help clinical management. As this is a clinical diagnosis, it’s important to be relatively confident that the diagnosis is not instead one of the many other disorders of connective tissue.

Arthrochalasia EDS

Major criteria are:

  1. Congenital bilateral hip dislocation;
  2. Severe GJH, with multiple dislocations/subluxations; and
  3. Skin hyperextensibility.

There are five minor criteria. Minimal criteria for aEDS are congenital bilateral hip dislocation (major criterion 1) plus either: skin hyperextensibility (major criterion 3); or severe GJH (major criterion 2) with at least two minor criteria.

    Dermatosparaxis EDS

    There are nine major criteria and eleven minor criteria. Minimal criteria suggestive of aEDS include the two major criteria of extreme skin fragility and characteristic craniofacial features, plus either: one other major criterion, or three minor criteria.

    Kyphoscoliotic eds

    Major criteria are:

    1. Congenital muscle hypotonia;
    2. Congenital or early onset kyphoscoliosis (progressive or non-progressive); and
    3. GJH with dislocations/subluxations (shoulders, hips and knees in particular)

    There are ten minor criteria, as well as gene-specific minor criteria (four for PLOD1 and four for FKBP14). Minimal criteria suggestive for kEDS are 1 and 2 of the major criteria—congenital muscle hypotonia and congential/early onset kyphoscoliosis—plus either: major criterion 3, or three minor criteria (either general of gene-specific).

    Brittle Cornea Syndrome (BCS)

    Major criteria are:

    1. Thin cornea, with or without rupture (central corneal thickness often <400 µm);
    2. Early onset progressive keratoconus;
    3. Early onset progressive keratoglobus; and
    4. Blue sclerae.

    There are fourteen minor criteria. Minimal criteria required to suggest BCS are the first major criterion, plus either: at least one other major criterion; or three minor criteria.

    Spondylodysplastic eds

    Major criteria are:

    1. Short stature (progressive in childhood);
    2. Muscle hypotonia (ranging from severe congenital, to mild later-onset); and
    3. Bowing of limbs.

    There are five general minor criteria, plus gene-specific criteria for B4GALT7, B3GALT6, and SLC39A13. Minimal criteria required to suggest a diagnosis for spEDS are the first and second major criteria, plus characteristic radiographic abnormalities and at least three minor criteria (either general or gene-specific).

    Musculocontractural EDS

    Major criteria are:

    1. Congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot);
    2. Characteristic craniofacial features, which are evident at birth or in early infancy; and
    3. Characteristic cutaneous features including skin hyperextensibility, easy bruisability, skin fragility with atrophic scars, increased palmar wrinkling.

    There are fifteen minor criteria. The minimum criteria required to suggest mcEDS are: at birth or in early childhood, major criteria 1 and 2; in adolescence and adulthood, major criteria 1 and 3.

    Myopathic Eds

    Major criteria are:

    1. Congenital muscle hypotonia, and/or muscle atrophy, that improves with age;
    2. Proximal joint contractures (knee, hip and elbow); and
    3. Hypermobility of distal joints.

    There are four minor criteria. The minimal criteria required to suggest a diagnosis of mEDS are the first major criterion plus either: one other major criterion, or three minor criteria.

    periodontal eds

    Major criteria are:

    1. Severe and intractable periodontitis of early onset (childhood or adolescence);
    2. Lack of attached gingiva;
    3. Pretibial plaques; and
    4. Family history of a first-degree relative who meets clinical criteria.

    There are eight minor criteria. The minimal criteria required to suggest pEDS are the first criterion or the second criterion, plus at least two other major criteria and one minor criterion.

    Pathogenetic Mechanisms Underlying the Ehlers Danlos Syndromes

    There is an additional genetic classification structure of the EDS into groups according to similarities in the way the responsible genes affect the body.

    Group A: Disorders of collagen primary structure and collagen processing, comprised of cEDS, vEDS, aEDS, dEDS, and cvEDS.

    Group B: Disorders of collagen folding and collagen crosslinking, comprised of kEDS-PLOD1 and kEDSS-FKB14.

    Group C: Disorders of structure and function of the myomatrix, comprised of clEDS and mEDS.

    Group D: Disorders of glycosaminoglycan biosynthesis, comprised of spEDS-B4GALT7, spEDS-b3GALT6, mcEDS-CHST14, and mcEDS-DSE.

    Group E: Defects in complement pathway, comprised of pEDS.

    Group F: Disorders of intracellular processes, comprised of spEDS-SLC39A13 and BCS.

    Group G: Unresolved forms of EDS, comprised of hEDS.

    Conditions no longer included in the EDS spectrum are occipital horn syndrome, fibronectin-deficient (EDS X), familial articular hypermobility (EDS XI), X-linked EDS with muscle hematoma (EDS V), and filamin A related EDS with periventricular nodular heterotopia.

    2017 Classification information courtesy of www.ehlers-danlos.com