What's on this Page
What is Ehlers Danlos Syndrome (EDS)
- Ehlers Danlos Syndrome are a group of related disorders.
- The etiology of EDS is due to various genetic defects in the collagen.
- Collagen is one of the major structural components of the body.
- Poor strength of collagen is responsible for the symptoms in patients with Ehlers Danlos Syndrome.
- Ehlers-Danlos Syndrome (EDS) is a group of genetic connective tissue disorders characterized by abnormalities in the structure and function of collagen, which is a major component of the body’s connective tissues. EDS affects the skin, joints, blood vessels, and other organs, leading to a wide range of symptoms.
Interesting Facts of Ehlers Danlos Syndrome
- Autosomal dominant inheritance of connective tissue (collagen) defects resulting in low bone mineral density and propensity to fracture
- Easy bruising, decreased skin elasticity, joint laxity and hypermobility, mitral and tricuspid prolapse
- Certain types do present with blue sclerae and dental abnormalities
- Biochemical and genetic analyses may be necessary to differentiate Ehlers-Danlos syndrome from milder forms of osteogenesis imperfecta
Synonyms
- EDS
- E-D Syndrome
Prevalence of EDS
The data from the Research shows that the total prevalence of the Ehlers Danlos syndromes is 1 in 2,500 to 1 in 5,000 people.
Recent clinical evidence proves that Ehlers Danlos Syndrome may be more common.
The conditions affects both males and females of all racial and ethnic backgrounds.
What causes Ehlers Danlos syndrome?
Connective tissue is everywhere in the body. It provides support and structure to other tissues and organs including bone, ligaments, tendons, blood vessels, lymphatic vessels, the tissue that holds the gastrointestinal tract in place, etc.
There are many proteins in connective tissue. One of the key proteins is collagen.
In the Ehlers Danlos syndromes, there are faults in the genes that determine how the body makes collagen, and/or in some subtypes other proteins that work alongside collagen.
This leads to the connective tissue becoming weaker.
Different tissues and organs can be affected in diverse ways depending on the genetic fault. This explains why there are several subtypes of EDS.
The genetic basis for hypermobile EDS (hEDS) is still unknown, so an hEDS diagnosis rests on the criteria and what your doctor finds during your examination.
Ehlers Danlos syndrome (EDS) is an intriguing group of inherited collagen and extracellular matrix protein disorders with a wide array of phenotypic expression.
EDS is most often an autosomal dominant trait, but up to 50% of patients can present as a de novo mutation.
Ehlers Danlos Syndrome has long been characterized by subtype using the 1997 Villefranche Classification system, an update from the original Berlin system initially published in 1988.
Subtypes of Ehlers Danlos Syndrome
There are several subtypes of EDS, each with its own specific features and genetic causes
Here are the Subtypes of Ehlers Danlos Syndrome
- Classic EDS
- Classical-like EDS
- Cardiac-valvular
- Vascular EDS
- Hypermobile EDS
- Arthrochalasia EDS
- Dermatosparaxis EDS
- Kyphoscoliotic EDS
- Brittle cornea syndrome
- Spondylodysplastic EDS
- Musculocontractural EDS
- Myopathic EDS
- Periodontal EDS
Symptoms of Classic EDS
Very Common Symptoms
- Atrophic scars
- Cigarette-paper scars
- Fragile skin
- Generalized joint laxity
- Hyperextensible skin
- Soft, doughy skin
- Striae distensae
Common Symptoms
- Chronic constipation
- Fatigue
- Gastroesophageal reflux
- Muscle spasm
- Muscle weakness
- Muscular hypotonia
- Nausea
- Osteopenia
- Poor wound healing
- Pulp stones
- Vomiting
Occasional Symptoms
- Abnormal cornea morphology
- Abnormal heart valve physiology
- Abnormality of the foot
- Abnormality of the temporomandibular joint
- Acrocyanosis
- Aortic root aneurysm
- Arterial dissection
- Arterial rupture
- Arteriovenous fistula
- Arthralgia
- Bladder diverticulum
- Blepharochalasis
- Bruising susceptibility
- Cervical insufficiency
- Dermatochalasis
- Dilatation of the cerebral artery
- Dislocated radial head
- Ecchymosis
- Epicanthus
- Hiatus hernia
- Hip dislocation
- Incisional hernia
- Inguinal hernia
- Joint swelling
- Limb pain
- Molluscoid pseudotumors
- Motor delay
- Osteoarthritis
- Patellar dislocation
- Pes planus
- Phalangeal dislocation
- Piezogenic pedal papules
- Premature birth
- Premature rupture of membranes
- Prematurely aged appearance
- Prolonged bleeding time
- Rectal prolapse
- Scoliosis
- Shoulder dislocation
- Subcutaneous spheroids
- Talipes equinovarus
- Umbilical hernia
- Uterine prolapse
Rare Symptoms
- Headache
- Mitral regurgitation
- Mitral valve prolapse
- Orthostatic hypotension
- Tricuspid valve prolapse
Symptoms of Hypermobile EDS
Very Common Symptoms
- Abnormality of the foot
- Acrocyanosis
- Arthralgia
- Elbow dislocation
- Fatigue
- Hip dislocation
- Hyperextensible skin
- Joint dislocation
- Joint hyperflexibility
- Myalgia
- Sleep disturbance
- Vertigo
- Wormian bones
Common Symptoms
- Arrhythmia
- Constipation
- Decreased nerve conduction velocity
- Depressivity
- Malabsorption
- Migraine
- Nausea and vomiting
- Osteoarthritis
- Pes planus
- Soft skin
- Thin skin
Ocasional Symptoms
- Abnormal palate morphology
- Abnormality of the dentition
- Abnormality of the gingiva
- Abnormality of the menstrual cycle
- Abnormality of the wrist
- Anorectal anomaly
- Aplasia/Hypoplasia of the abdominal wall musculature
- Apnea
- Arterial dissection
- Atypical scarring of skin
- Cystocele
- Decreased fertility
- Dilatation of the ascending aorta
- Epicanthus
- Gastroesophageal reflux
- Gastrointestinal dysmotility
- Genital hernia
- Gingival overgrowth
- Gingivitis
- Inguinal hernia
- Keratoconjunctivitis sicca
- Keratoconus
- Limitation of joint mobility
- Microdontia
- Osteolysis
- Paresthesia
- Ptosis
- Scoliosis
- Subcutaneous nodule
- Tendon rupture
- Umbilical hernia
- Venous insufficiency
Symptoms of Brittle cornea syndrome
Very Common Symptoms
- Corneal dystrophy
- Decreased corneal thickness
- High myopia
- Hyperextensible skin
- Keratoglobus
- Soft skin
Common Symptoms
- Abnormality of hair pigmentation
- Blue sclerae
- Bruising susceptibility
- Conductive hearing impairment
- Corneal scarring
- Gait disturbance
- Joint hyperflexibility
- Myalgia
- Osteoporosis
- Sensorineural hearing impairment
- Visual loss
Ocasional Symptoms
- Abnormality of epiphysis morphology
- Abnormality of the dentition
- Arachnodactyly
- Camptodactyly
- Cleft palate
- Corneal erosion
- Glaucoma
- Hallux valgus
- Hernia
- Hip dysplasia
- Increased susceptibility to fractures
- Mitral valve prolapse
- Neonatal hypotonia
- Pes planus
- Pulmonic stenosis
- Retinal detachment
- Scoliosis
Symptoms of Arthrochalasia Ehlers-Danlos syndrome
Very Common Symptoms
- Abnormality of subcutaneous fat tissue
- Aphasia
- Avascular necrosis of the capital femoral epiphysis
- Coxa valga
- Coxa vara
- Dysphasia
- Echolalia
- Hip dislocation
- Hip dysplasia
- Hyperextensible skin
- Joint dislocation
- Joint hyperflexibility
- Joint stiffness
- Muscle flaccidity
- Muscular hypotonia
- Mutism
- Scarring
- Severe short stature
- Thin skin
Common Symptoms
- Depressed nasal bridge
- Epicanthus
- Hypertelorism
- Micrognathia
- Retrognathia
- Scoliosis
Ocasional Symptoms
- Femoral hernia
- Inguinal hernia
Symptoms of Dermatosparaxis Ehlers-Danlos syndrome
Very Common Symptoms
- Abnormal joint morphology
- Abnormality of subcutaneous fat tissue
- Aphasia
- Avascular necrosis of the capital femoral epiphysis
- Coxa valga
- Coxa vara
- Dysphasia
- Echolalia
- Esophagitis
- Excessive wrinkled skin
- Gastroesophageal reflux
- Hernia
- Hiatus hernia
- Hip dislocation
- Hip dysplasia
- Hyperextensible skin
- Joint dislocation
- Joint hyperflexibility
- Joint stiffness
- Muscular hypotonia
- Mutism
- Osteomalacia
- Osteopenia
- Osteoporosis
- Prolonged bleeding time
- Rickets
- Scarring
- Severe short stature
- Thin skin
Common Symptoms
- Depressed nasal bridge
- Epicanthus
- Femoral hernia
- Inguinal hernia
- Micrognathia
- Retrognathia
- Scoliosis
- Kyphoscoliotic form
- Autosomal recessive disorder that can present similarly to Marfan syndrome with marfanoid body habitus, joint hypermobility, kyphoscoliosis, mitral valve prolapse, and risk for rupture of medium arteries
- Known genetic problems associated with the syndrome include abnormalities in PLOD (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1) and ZNF469 (zinc finger protein 469)
- Additional characteristic features of the syndrome include blue sclerae, severe hypotonia at birth, ocular fragility, and characteristic skin findings (eg, friable, hyperextensive skin; easy bruising; thin scars)
- Differentiated from Marfan syndrome by clinical presentation; typically presents at birth or within the first year of life
- Definitive diagnosis is made by increased ratio of deoxypyridinoline to pyridinoline cross-links in urine as measured by high-performance liquid chromatography
- Vascular type
- Autosomal dominant disorder with characteristic features that include translucent skin, extremely fragile skin, small joint laxity, easy bruising, hollow organ rupture, dystrophic scars, and characteristic facies (eg, prominent eyes, pinched appearance)
- As with Marfan syndrome, there is a tendency toward aneurysm and/or dissection of medium and large arteries throughout the body
- Differentiated from Marfan syndrome via variations in clinical presentation; there is no particular tendency for involvement of aortic root
- Definitive diagnosis is made via molecular genetic testing by presence of a characteristic pathogenic variant in COL3A1 or COL3A2 gene
How is this condition diagnosed?
The crucial aspect to treat EDS is the timely diagnosis which is very important because of the very fact that though this condition cannot be cured completely, they are fully treatable.
- Classic EDS – molecular testing detects the genes encoding type V collagen (COL5A1 and COL5A2), the mutation of which is responsible for the Classic EDS
- Classical-like EDS – molecular testing detects the Tenascin XB gene, which is the only gene associated with Classical-like EDS.
- Cardiac-valvular – molecular testing detects the COL1A2 gene.
- Vascular EDS – molecular testing detects the COL3A1 gene.
- Hypermobile EDS – The diagnosis of hypermobile EDS (hEDS) is primarily clinical. As there is no molecular and genetic cause yet identified, there is no test available for almost all with hEDS.
- Arthrochalasia EDS – molecular testing detects the COL1A1 or COL1A2 genes.
- Dermatosparaxis EDS – molecular testing detects the ADAMTS2 gene.
- Kyphoscoliotic EDS (kEDS) – The majority of patients with kEDS harbor biallelic mutations in PLOD1; recently, biallelic mutations have been identified in FKBP14 in patients. Laboratory confirmation should start with a urine test using high-performance liquid chromatography (to evaluate the ratio of lysyl-pyridinoline to hydroxylysyl-pyridinoline crosslinks; a normal ratio is ~0.2, whereas kEDS-PLOD1 range is 2-9).
- Brittle cornea syndrome – molecular testing detects the ZNF469 or PRDM5 genes.
- Spondylodysplastic EDS – molecular testing detects the B4GALT7, B3GALT6, and SLC39A13 genes.
- Musculocontractural EDS – Musculocontractural EDS is caused by biallelic mutations in CHST14 detected by molecular testing
- Myopathic EDS (mEDS)- mEDS is caused by heterozygous or biallelic mutations in COL12A1 detected by molecular testing
- Periodontal EDS (pEDS) – pEDS is caused by heterozygous gain-of-function mutations in C1R or C1S detected by molecular testing
- Physical testing using the Beighton Scale
- The Beighton Scale is to assess how mobile your joints are, a search for abnormal scarring and testing your skin to determine what it feels like and how much it stretches.
- Molecular testing results are useful to provide the basis for genetic counseling for our families also helpful in the guidance on treatment options.
How is this condition treated?
- Treatment for Ehlers-Danlos Syndrome focuses on managing symptoms and preventing complications.
- It may involve a multidisciplinary approach involving medical professionals from various specialties, including geneticists, orthopedic surgeons, physical therapists, pain specialists, and cardiologists.
- Treatment strategies may include physical therapy, pain management, bracing or splinting, surgical interventions when necessary, and genetic counseling.
Differential Diagnosis
Several disorders closely mimic EDS in clinical presentation. The following is a non-exhaustive list of conditions that may be considered in the differential diagnosis of a patient’s presentation.
- Hypermobility spectrum disorders (HSD)
- Occipital horn syndrome (OHS)
- Loeys-Dietz syndrome (LDS)
- Familial aortic aneurysm (FAA)
- Familial hypermobility syndrome (FHS)
- Marfan syndrome (MFS)
- Brittle cornea syndrome 2 (BCS2)
What is the prognosis of Ehlers Danlos Syndrome?
- Fortunately, there is treatment for symptoms of EDS.
- There is no cure for the Ehlers Danlos syndrome, hence preventative measures are the life savers.
- The prognosis usually depends on the type of Ehlers Danlos syndrome.
- Those affected with the Vascular Ehlers Danlos syndrome will have lower Life expectancy as there are higher possibilities of rupture of visceral organs and blood vessels.
- In the other subtypes, the life expectancy is usually not affected. The severity can be a mild or moderate range within a family.
- Each affected individual of Ehlers Danlos syndrome will be unique.