Ehlers-Danlos syndrome (EDS) is a heterogeneous group
of heritable connective tissue disorders characterized by articular
hypermobility, skin extensibility and tissue fragility. Individuals
with EDS have a defect in their connective tissue. It is this tissue
that provides support to many body parts such as the skin, muscles,
ligaments and organs. The fragile skin and unstable joints found in EDS
are due to faulty collagen. Collagen is a protein that acts like glue
in the body adding strength and elasticity to connective tissue.
There are six major types of EDS. The different types of EDS are
classified according to the signs and symptoms that are manifested.
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 have a
child with Classical Type EDS. More detailed information can be
found in our Medical Professionals Section.
Hypermobility (Formerly EDS Type III)
Joint hypermobility
is the dominant clinical manifestation. Generalized joint hypermobility
that affects large (elbows, knees)and small (fingers and 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 (hyperextensibility and/or smooth velvety skin) as
well as bruising tendencies in the Hypermobility Type are present but
variable in severity.
Chronic joint and limb pain is a common complaint amongst individuals
with the Hypermobility Type. Skeletal X-rays are normal.
Musculoskeletal pain is early onset, chronic and may be debilitating.
The anatomical distribution is wide and tender points can sometimes be
elicited.
To date, no distinctive biochemical collagen finding has been
identified by researchers. The Hypermobility Type of EDS is inherited
in an autosomal dominant manner.
Classical (Formerly EDS Types I & II)
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 expression. The
skin is smooth and velvety with the evidence of tissue fragility and
easy bruisability. 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. The Classical Type of EDS is
inherited in an autosomal dominant manner.
Vascular (Formerly EDS Type IV)
This 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. This 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 maybe complicated by intra-partum uterine rupture
and pre- and postpartum arterial bleeding.
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; arteriovenousfistula (an
opening between an artery and vein), carotid-cavernousfistula;
pneumothorax (collapse of a lung) /pneumohemothorax (collapse of a lung
with a collection of air or gas and blood); gingivalrecession 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.
Kyphoscoliosis (Formerly EDS Type VI)
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 present with
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 (Formerly EDS Type VII A&B)
Congenital hip dislocation has been present in all
biochemically proven individuals with this type of EDS. Severe
generalized joint hypermobility with recurrent subluxations are seen in
individuals with this type of EDS. 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.
Dermatosparaxis (Formerly EDS Type VIIC)
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.
Other
The current EDS type V (X-linked) has been described
in a single family. It is a rare variant and the molecular basis of
which remains unknown.
The current EDS type VIII is similar to the Classical Type except that
in addition it presents with periodontal friability. This is a rare
type of EDS. The existence of this syndrome as an autonomous entity is
uncertain.
The EDS type IX was previously redefined as "Occipital Horn syndrome",
an X-linked recessive condition allelic to Menkes syndrome. This was
previously removed from the EDS classification.
The current EDS type X has been described in only one family.
The EDS type XI termed "Familial Joint Hypermobility syndrome" was
previously removed from the EDS classification. Its relationship to the
EDS is not yet defined.
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