Types Overview
There are six major types of EDS as determined by the Villefranche defintions of 1997, each caused by a mutation in a different collagen-encoding gene, leading to the differentiation of symptoms between the types. There is some significant overlap in the symptoms of EDS and the idea of switching to more of a spectrum-like definition (such as has been created for autism) has been discussed in recent literature. The overviews below list the most common symptoms for each type, but a larger list of symptoms that can be casued by EDS can be found here.
These overviews are meant for a basic synopsis of each type, for a more complete definition of a particular type, visit the Additional Resources page.
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Arthrochalasia (Formerly Known as Types VII A and VII B)
Overview:
Arthrochalasia type EDS is one of the more rare subtypes with a prevalence of 1 affected in every 1,000,000 people. Arthrochalasia is characterized by bilateral congential hip dislocation, extreme hyperflexibility in small and large joints, thoracolumbar scoliosis, short stature, and muscle hypotonia. Arthrochalasia is caused by a mutation in either COL1A1 or COL1A2, the genes controlling type I collagen production.
Inheritance:
Arthrochalasia is inherited in an autosomal dominant pattern (only one copy of the mutated gene is needed to cause the disorder). Like in classic and vascular types, de novo (a change in the DNA that is newly arisen in the individual and was not inherited by that individual) mutations can occur to cause this type, but inherited mutation is much more common. Because of the autosomal dominant inheritance pattern, there is a 50% chance that a person with classic EDS will have a child with the syndrome.
Common Clinical Presentations:
Hallmark symptoms
- congenital bilateral dislocation of the hips
- recurrent dislocations of the small and large joints
- pronounced joint laxity
- muscle hypotonia (low muscle tone)
Diagnosis:
Diagnosis is made based on clinical presentation and medical history, as well as family history. Clinical diagnosis is confirmed with molecular studies confirming the skipping or partial skipping of exons 5 and/or 6 on the COL1A1 or COL1A2 genes.
Classic (Formerly Known as Types I and II)
Overview:
Classic type EDS is one of the more common type of EDS, affecting an estimated 1 in 20,000. Classic EDS is caused by a mutation in one of the two genes responsible for the protein structure of type V collagen. The mutation results in a dysfunctional or nonfunctional collagen protein.
Inheritance:
Classic EDS is inherited in an autosomal dominant (only one copy of the faulty gene is needed to cause the disorder) pattern, although it is estimated that 50% of cases are the result of a de novo mutation (a change in the DNA that is newly arisen in the individual and was not inherited by that individual). Because of the autosomal dominant inheritance pattern, there is a 50% chance that a person with classic EDS will have a child with the syndrome.
Common Clinical Presentations:
- Skin hyperextensibility
- joint hypermobility
- frequent and recurrent dislocations and subluxations
- easy bruising
- widespread tissue fragility
- abnormal scarring
- delayed wound healing (due to reopening of wound with tissue fragility)
- mitral valve prolapse
- pregnancy complications related to tissue and membrane fragility
- chronic, widespread musculoskeletal pain related to recurrent tissue trauma
- hernias, particularly in children
- flat feet
- joint instability
- gastrointestinal issues
Diagnosis:
- Diagnosis is dependent on clinical and family history as well as as physical examination
- Approximately 50% of cases have an identifiable mutation in the COL5A1 or COL5A2 gene that can be found through genetic testing
Dermatosparaxis (Formerly Known as Type VIIC)
Overview:
Dermatosparaxis type EDS one of the most rare types of EDS, affecting 1 in 1,000,000. Dermatosparaxis is caused by a mutation in ADAMTS2 gene, which produces an enzyme that alters the collagen protein to make it functional. The mutation renders the enzyme produced by ADAMTS2 useless, leading to weakened collagen. There is significant risk of internal organ rupture.
Inheritance:
Dermatosparaxis is inherited in an autosomal recessive pattern, meaning that both parents must be carriers of the mutated gene and that both copies must be present to cause the syndrome. Because this type is autosomal recessive, affected patients are unlikely to have children with the disease unless their child’s other parent is a carrier or is also affected.
Common Clinical Presentations:
Unlike other types of EDS, which can go unnoticed for years, dermatosparaxis is prominent in the first years of life.
Hallmark symptoms:
- Soft, doughy skin
- extremely fragile skin
- easy bruising
- saggy, wrinkly skin that has redundant (extra) folds
- loose joints which delay gross motor development
- infants are born with umbilical hernias
Other symptoms include:
- large fontanelles
- premature rupture of the membranes
- blue sclerae
- puffy eyes
- short fingers
- micrognathia (small jaw)
- dental complications such as
- early tooth loss
- severe periodontitis
- abnormal morphology of deciduous teeth (baby teeth), particularly the molars
- permanent teeth show dental agenesis (missing or malformed teeth)
- small adult teeth
- tooth discoloration
- dental dysplasia (roots of teeth are shortened)
- tooth pulp obliteration
Diagnosis:
Dermatosparaxis type can be identified through genetic testing, or may be diagnosed on clinical presentation alone. The symptoms of dermatosparaxis are unique enough in combination to diagnose.
Hypermobility (Formerly Known as Type III)
Overview:
Hypermobility type EDS is the most common form of EDS at 1-5 in 10,000. Hypermobility type overlaps with Joint Hypermobility Syndrome (JHS) which some researchers claim to be separated from EDS but others claim that JHS is the same as EDS hypermobility.
Inheritance:
Hypermobility type EDS is inherited in an assumed autosomal dominant pattern. The gene that causes hypermobility type is yet unknown.
Common Clinical Presentations:
Hallmark symptoms are
- generalized joint hypermobility, affecting the smaller joints particularly
- joint instability
- widespread musculoskeletal pain
- minor skin features
- mucosal membrane fragility
- nosebleeds
- easily damaged gums
Other symptoms
- chronic, sometimes debilitating, pain
- cardiovascular involvement
- easy bruising
- increased risk of aortic root dilation
- possibility of minor mitral valve prolapse
- gastrointestinal complications
- increased organ fragility but not as severe as other types
Diagnosis:
The gene that causes hypermobility is yet unknown, so genetic testing is currently unavailable. Diagnosis is made based on the clinical presentation and patient history as well as positive family history.
Kyphoscoliosis (Formerly Known as Type VI)
Overview:
Kyphoscoliosis type EDS is also more rare than other types, though the incidence rate has not been defined. As the name suggests, kyphoscoliosis is the defining characteristic of this type. Kyphoscoliotic EDS is caused by a mutation in the PLOD1 gene, which controls the production of an enzyme that activates the cross-linking of collagen fibers and thus giving them their connective function. With the mutation, the enzyme produced by the PLOD1 gene is inactive, leading to a loss of collagenous connective function.
Inheritance:
Kyphoscoliosis type EDS is inherited in an autosomal recessive manner, meaning that both parents must be carriers of the mutated gene and that both copies must be present to cause the syndrome. Because this type is autosomal recessive, affected patients are unlikely to have children with the disease unless their child’s other parent is a carrier or is also affected.
Common Clinical Presentations:
The major presenting symptom of kyphoscoliotic eds is kyphoscoliosis, abnormal bends in the spine in both the coronal and sagittal regions, a combination of kyphosis and scoliosis, that can be present at birth, but almost always develops in the first year of life.
Other symptoms:
- generalized joint hypermobility
- congenital hypotonia (low muscle tone present at birth)
- congenital, progressive kyphoscoliosis
- scleral fragility and ocular globe rupture
- tissue fragility
- abnormal scarring
- arterial fragility and rupture
- marfanoid habitus
- constellation of marfan syndrome-like symptoms including long, thin body with long, spider- like fingers, and arm span that is greater than height, but not including the more severe deformities of the chest, lens dislocation, and risk of aortic dissection
- osteopenia/osteoporosis
Diagnosis:
Kyphoscoliosis type EDS can be diagnosed based on clinical presentation and history, but also with a High-Performance Liquid Chromatography Test (HPLC Test) that measures the ratio of different types of crosslinks in the urine. It can also be diagnosed with an assay of lysyl hydroxylase enzyme activity in skin fibroblasts.
Vascular (Formerly Known as Type IV)
Overview:
Vascular EDS is the only type with a high concern for death due to the effects of the syndrome. Vascular EDS mainly affects the vascular tissue, leading to a high risk of arterial rupture and a variety of cardiac issues. Vascular EDS is caused by a mutation in the gene that controls type III collagen production--COL3A1.
Inheritance:
Vascular EDS is an autosomal dominant (only one copy of the faulty gene is needed to cause the disorder) pattern, although it is estimated that 50% of cases are the result of a de novo mutation (a change in the DNA that is newly arisen in the individual and was not inherited by that individual). Because of the autosomal dominant inheritance pattern, there is a 50% chance that a person with classic EDS will have a child with the syndrome.
Common Clinical Presentations:
Hallmark Symptoms:
- thin, translucent skin
- arterial fragility and rupture
- organ fragility and rupture (particularly of the intestines and uterus)
- extensive bruising
- characteristic facial features (thin lips, small chin, thin nose, large eyes)
Other symptoms:
- hypermobility of small joints
- tendon/muscle rupture
- early-onset varicose veins
- pneumothorax
- chronic joint dislocations/subluxations
Diagnosis:
Vascular EDS is diagnosed based on clinical presentation and history, family history, and confirmed with genetic testing.
