There are six distinct types of EDS currently identified. All share joint laxity, soft skin, easy bruising, and some systemic manifestations. Each type is thought to involve a unique defect in connective tissue, although not all of the genes responsible for causing EDS have been found.
These six types are defined according to the signs and symptoms that are manifested, in a set of major and minor diagnostic criteria for each type. Each type of EDS is a distinct disorder that "runs true" in a family. This means that an individual with Vascular Type EDS will not normally have a child with Classical Type EDS. There a number of mutations identified as Ehlers-Danlos syndromes since the 1997 diagnostic criteria; these lie outside the classifications and can be located through the OMIM/Online Mendelian Inheritance in Man® database from Johns Hopkins University.
Vascular
Type of EDS
Vascular Type is generally regarded as the most serious form of EDS due to the possibility of arterial or organ rupture. The skin is usually thin and translucent with veins being seen through the skin, which is most apparent over the chest and abdomen. There are certain facial characteristics present in some affected individuals. These manifestations include large eyes, thin nose, lobeless ears, short stature and thin scalp hair. Also evident is a decrease in subcutaneous tissue, particularly in the face and extremities. Minor trauma can lead to extensive bruising.
Arterial/intestinal/uterine fragility or rupture commonly arise in this type of EDS. Spontaneous arterial rupture has a peak incidence in the third or fourth decade of life, but may occur earlier. Midsize arteries are commonly involved. Arterial rupture is the most common cause of sudden death. Acute diffuse or localized abdominal or flank pain is a common presentation of arterial or intestinal rupture. Life expectancy is shortened with a majority of individuals living only into their forties. Pregnancies may be complicated by intra-partum uterine rupture and pre- and postpartum arterial bleeding. Treatments are available which may help extend life, and surgical interventions are improving.
Joint hypermobility is usually limited to the digits. Tendon and muscle rupture can occur. Talipes equinovarus (clubfoot) is frequently seen at birth. Other manifestations that may be found in the Vascular Type include: acrogeria (premature aging of the skin of the hands and feet); early onset varicose veins; arteriovenous fistula (an opening between an artery and vein), carotid-cavernous fistula; pneumothorax (collapse of a lung) /pneumohemothorax (collapse of a lung with a collection of air or gas and blood); gingival recession and complications during and after surgery (i.e. wound dehiscence).
The Vascular Type of EDS is caused by structural defects in the proa1(III) chain of collagen type III encodes by COL3A1. This type of EDS is inherited in an autosomal dominant manner. A skin biopsy can diagnose this type of EDS.
Hypermobility
Type of EDS
Joint hypermobility is the dominant clinical manifestation. Generalized joint hypermobility that affects large (elbows, knees) and small (fingers, toes) joints is evident in the Hypermobility Type. Recurring joint subluxations and dislocations are common occurrences. Certain joints, such as the shoulder, patella and temporomandibular joint dislocate frequently. The skin involvement (smooth velvety skin with or without hyperextensibility) as well as bruising tendencies in the Hypermobility Type are present but quite variable in severity.
Chronic pain is a well-established and cardinal manifestation of Hypermobility EDS and it is common for pain to be out of proportion to physical and radiological findings. The origin of the pain is not clearly understood, but some of the likely causes include muscle spasm (tender points are sometimes present) and degenerative arthritis; neuropathic pain is also common.
To date, there is no distinctive biochemical collagen finding identified for the majority of Hypermobility cases. The Hypermobility Type of EDS is inherited in an autosomal dominant manner.
Dermatosparaxis
Type of EDS
Individuals with Dermatosparaxis Type EDS have severe skin fragility and substantial bruising. Wound healing is not impaired and the scars are not atrophic. The skin texture is soft and doughy. Sagging, redundant skin is evident. The redundancy of facial skin results in an appearance resembling cutis laxa. Large hernias (umbilical, inguinal) may also be seen. The number of patients reported with this type of EDS is small.
Dermatosparaxis Type EDS is caused by a deficiency of procollagenI N-terminal peptidase. It is inherited in an autosomal recessive manner. A skin biopsy can diagnose this type of EDS.
Classical
Type of EDS
Marked skin hyperextensibility (stretchy) with widened atrophic scars and joint hypermobility are found in the Classical Type of EDS. The skin manifestations range in severity from mild to severe. The skin is smooth and velvety along with evidence of fragility and a tendency to bruise easily. Examples of tissue extensibility and fragility include hiatal hernia, anal prolapse in childhood and cervical insufficiency. Hernias may be a post-operative complication. Scars are found mostly over pressure points such as the knees, elbows, forehead, and chin. Molluscoid pseudo tumors (calcified hematomas) associated with scars are frequently found over pressure points such as the elbows, and spheroids (fat containing cysts) are usually found the on the forearms and shins.
Complications of joint hypermobility include sprains, dislocations/subluxations and pes planus (flat foot) to name a few. Recurrent joint subluxations are common in the shoulder, patella and temporomandibular joints. Muscle hypotonia and delayed gross motor development may also be evident.
Clinical Testing - Abnormal electrophoretic mobility of the proa1(V) or proa2(V) chains of collagen type V has been detected in several but not all families with the Classical Type, although recent work may have brought molecular diagnosis rate to over 90%. The Classical Type of EDS is inherited in an autosomal dominant manner.
Kyphoscoliosis
Type of EDS
Generalized joint laxity and severe muscle hypotonia (weak muscle tone) at birth are seen in this type of EDS. The muscular hypotonia can be very pronounced and leads to delayed gross motor development. Individuals with the Kyphoscoliosis Type exhibit scoliosis at birth that is progressive. The phenotype is most often severe, frequently resulting in the loss of ambulation in the second or third decade. Scleral fragility may lead to rupture of the ocular globe after minor trauma.
Tissue fragility including atrophic scars and easy bruising may be seen in the Kyphoscoliosis Type. Spontaneous arterial rupture can occur. Other findings may include: marfanoid habitus (Marfan-like features); micro cornea (abnormally small cornea); and radiologically considerable osteopenia (diminished amount of bone tissue).
Kyphoscoliosis Type EDS is the result of a deficiency of lysylhydroxylase (PLOD), which is a collagen-modifying enzyme. This type of EDS is inherited in an autosomal recessive manner. Kyphoscoliosis Type can be diagnosed through a urine test.
Arthrochalasia
Type of EDS
Congenital hip dislocation has been present in all biochemically proven individuals with this type of EDS. Individuals often have severe generalized joint hypermobility with recurrent subluxations. Other manifestations of this type may include: skin hyperextensibility with easy bruising; tissue fragility including atrophic scars; muscle hypotonia; kyphoscoliosis; and radiologically mild osteopenia.
The Arthrochalasia Type is caused by mutations leading to deficient processing of the amino-terminal end of proa1(I) [type A] or proa2(I)[type B] chains of collagen type I. It is inherited in an autosomal dominant manner. A skin biopsy can also diagnose this type of EDS.
Forms of EDS within this unclassified category may present with soft, mildly stretchable skin, shortened bones, chronic diarrhea, joint hypermobility and dislocation, bladder rupture, or poor wound healing. Inheritance patterns within this group include X-linked recessive, autosomal dominant and autosomal recessive. Examples of these syndromes include: Beasley-Cohen Type, Progeroid form - B4GALT7, Friedman-Harrod Type, Tenascin-X deficiency - TNXB and Musculocontractural type - CHST14.
