Types Of Ehlers-Danlos Syndrome (EDS)

Ehlers-Danlos syndrome (EDS) is characterized by a group of connective tissue disorders caused by a mutation in genes. It is generally identified by joint hypermobility, skin elasticity, and tissue fragility. Ehlers-Danlos syndrome is further divided into 13 subtypes depending on the specific gene mutation, signs and symptoms, and protein involved. There is very diversity in symptoms of Ehlers-Danlos syndrome from person to person. Diagnostic criteria are only made to differentiate Ehlers-Danlos syndrome from other disorders with similar symptoms.

HYPERMOBILE EHLERS-DANLOS SYNDROME (hEDS)

Hypermobile Ehlers-Danlos Syndrome is presented by hypermobility of joints, slight elasticity of skin, and chronic musculoskeletal pain. It is the most common type of Ehlers-Danlos syndrome caused by defect in protein collagen. The specific type of gene that is responsible for causing Hypermobile Ehlers-Danlos syndrome is still unknown. The onset of Hypermobile Ehlers-Danlos Syndrome is usually during childhood and teenage.

Symptoms of Hypermobile Ehlers- Danlos Syndrome

• Hypermobility of joint
• Frequent joint dislocation and subluxation
• Dysfunction of the autonomic nervous system
• Slightly elastic skin
• Rupture of uterus during pregnancy
• Gastrointestinal problems
• Cardiovascular issues

Diagnosis of Hypermobile Ehlers-Danlos syndrome

As there is no specific test available for the diagnosis of Hypermobile Ehlers-Danlos Syndrome so diagnosis will be made on presence of characteristic signs and symptoms.

• Beighton score system
• Family History
• Musculoskeletal complications

CLASSICAL EHLERS-DANLOS SYNDROME (cEDS)

Classical Ehlers-Danlos Syndrome is presented by skin hyperextensibility with velvety skin appearance and scarring. It is the second most common type of Ehlers-Danlos syndrome caused by a defect in protein collagen. Classical Ehlers-Danlos Syndrome is resulted in by mutation in two genes COL5A1 and COL5A2 which codes type V collagen.

 Symptoms of Classical Ehlers-Danlos Syndrome

• Velvety skin that is highly susceptible to nursing
• Very elastic skin
• Abnormal healing of wounds that results in atrophic scars
• Joint dislocation and subluxation due to hypermobility
• Hypotonia
• Tissue fragility may lead to many complications like hernias
• Rupture of uterus and vessels in pregnancy

Diagnosis of Classical Ehlers-Danlos Syndrome

The diagnosis is typically based on the signs and symptoms present in a specific patient. In ninety percent of cases, classical Ehlers-Danlos syndrome is caused by deficit information of type V collagen. Following tests are performed to confirm the diagnosis of classical Ehlers- Danlos Syndrome:

• Genetic testing to check the gene mutation in specific cases
• Skin biopsy is performed with diagnosis is not confirmed by genetic testing or if genetic testing is unavailable. Collagen made one-third of the body parts including ligaments, tendons, and muscles. This test doesn’t confirm the diagnosis but helps rule out other forms of Ehlers-Danlos Syndrome.

Classical Like Ehlers-Danlos Syndrome (clEDS)

Classical like Ehlers-Danlos Syndrome is presented by generalized joint hypermobility, spontaneous ecchymoses, and skin hyperelasticity which is results due to mutation in the TNXB gene. This gene helps in the formation of protein tenascin-X which assists in the function of collagen. Tenascin-X supports the structure of muscles, joints, and bones therefore, defects in this protein results in joint hypermobility and soft skin.

Symptoms of classical-like Ehlers-Danlos syndrome

• The weakness of the upper arm and leg muscles
• Joint hypermobility
• Skin bruising
• Muscle aches
• Hyperelastic and thin skin
• Skeleton muscle degeneration
• Damage to sensory neurons

Diagnosis of Classical like Ehlers-Danlos Syndrome

The diagnosis of classical-like Ehlers-Danlos Syndrome is also based on physical examination of signs and symptoms plus genetic testing. Following steps are followed to diagnose classical type Ehlers-Danlos Syndrome:

• More than eighty percent of the people with classical-like Ehlers-Danlos Syndrome have joint hypermobility so the Beighton score is used to identify the extent to which the patent bends his joint comfortably.
• Genetic testing is done to identify the defects in the TNXB gene.

Cardiac Valvular Ehlers-Danlos Syndrome (cvEDS)

The cardiac valvular Ehlers-Danlos Syndrome is presented by severe progressive cardiac-valvular problems, skin hyperelasticity, and joint hypermobility. Cardiac valvular Ehlers-Danlos Syndrome is caused by a mutation in COL1A2 which carries the instruction for the formation of type 1 collagen. Defect in this gene results in defects in the structure of type 1 collagen which causes symptoms associated with cardiac valvular Ehlers-Danlos Syndrome.

Symptoms Of Cardiac Valvular Ehlers-Danlos Syndrome

• Progressive weakening of heart valves
• Abnormal curvature of the spine called scoliosis
• Hypertension
• Hyperelastic and thin prone to bruises
• Hypermobile joints result in frequent dislocation and subluxation

Diagnosis Of Cardiac Valvular Ehlers-Danlos Syndrome

Following tests are performed to confirm the diagnosis of cardiac valvular Ehlers-Danlos Syndrome:

• Skin biopsy
• Genetic testing
• An electrocardiogram is used to detect heart defects

VASCULAR EHLERS-DANLOS SYNDROME (vEDS)

Vascular Ehlers-Danlos Syndrome is presented by fragility of heart, intestine, and uterus; translucent skin; abnormal facial appearance, wrinkle on extremities especially on hands. It is caused by a mutation in the COL3A1 gene in most cases and rarely by the mutation in COL1A1. COL3A1 gene carries the instruction for the formation of type lll collagen. This type of collagen is found in skin, tissues, intestinal walls, lungs, and walls of blood vessels.

 Symptoms Of Vascular Ehlers-Danlos Syndrome

• Fragile tissues of arteries, intestines, and organ that can rupture
• Thin lips, small chin, large eyes, and thin nose are characteristic facial features
• Premature aging or wrinkle on hands and feet’s
• Collapsed lungs
• Dislocation and subluxation of joints
• Ebbing gums

Diagnosis Of Vascular Ehlers-Danlos Syndrome

Following tests are performed to confirm the diagnosis of vascular Ehlers-Danlos Syndrome:

• Genetic testing to confirm the mutation in COL3A1 or COL1A1 gene.
• Molecular genetic testing is performed to identify the defects in type lll collagen.

ARTHROCHALASIA EHLERS-DANLOS SYNDROME (aEDS)

Arthrochalasia Ehlers-Danlos Syndrome is presented by congenital hip joint dislocation, hypotonia, and kyphoscoliosis. This type is caused by mutation in the COL1A1 and COL2A1 genes. These genes carry the information for the formation of type 1 collagen. Type 1 collagen is the most abundant form of collagen present in the human body, abnormal formation of which causes deformities of lines, skin, ligaments, cartilage, and tendons.

Symptoms Of Arthrochalasia Ehlers-Danlos Syndrome

• Severe joint hypermobility
• Hyperextensible skin
• Congenital hip joint dislocation
• Hypotonia
• Kyphoscoliosis
• Abnormal facial features like wide-spaced eyes, epicanthal folds, and micrognathia.

Diagnosis of Arthrochalasia Ehlers-Danlos Syndrome

The diagnosis of arthrochalasia Ehlers-Danlos Syndrome is based on the presence of specific signs and symptoms. To confirm the diagnosis of this type of Ehlers-Danlos Syndrome following tests are performed:

• Skin biopsy
• Genetic testing

DERMATOSPARAXIS EHLERS-DANLOS SYNDROME (dEDS)

Dermatosparaxis Ehlers-Danlos Syndrome is presented by soft and doughy skin which is extremely fragile and redundant. It is caused by a mutation in the ADAMTS2 gene which carries the information of the formation of an enzyme. This enzyme helps in the formation of many procollagen molecules. Mutation in ADAMTS2 alters the function of enzymes which then retards the processing of procollagen.

 Symptoms of Dermatosparaxis Ehlers-Danlos Syndrome

• Extreme skin fragility with congenital skin tears
• Redundant and saggy skin
• Severe bruising
• Umbilical hernia
• Postnatal growth retardation
• Joint hypermobility
• Short stature

Diagnosis of Dermatosparaxis Ehlers -Danlos Syndrome

The diagnosis of dermatosparaxis is based on the presence of specific clinical features.

• Skin biopsy
• Molecular testing
• Biochemical protein-based testing
• Prenatal testing

KYPHOSCOLIOTIC EHLERS-DANLOS SYNDROME (kEDS)

Kyphoscoliotic Ehlers-Danlos Syndrome is presented by progressive kyphoscoliosis, hypotonia, and fragility of the sclera. It is caused by the mutation in the PLOD1 gene or FKBP14 gene. These genes provide instruction for the formation of an enzyme that encodes specific collagen molecules. The enzyme form with the help of these genes provides information for the proper interaction of one collagen molecule with the other. Improper interaction between the collagen molecules weakens the connecting tissue and produces symptoms of kyphoscoliotic Ehlers Danlos -Syndrome.

 Symptoms Of Kyphyscoliotic Ehlers-Danlos Syndrome

• Progressive kyphoscoliosis
• Fragility of sclera
• Unusually small cornea
• Low density of bones
• Hypermobility of joints
• Hyperextensible skin
• Hypotonia

Diagnosis Of Kyphyscoliotic Ehlers-Danlos Syndrome

Following teat are performed to confirm the diagnosis of kyphyscoliotic Ehlers-Danlos Syndrome

• Urine test to confirm the absence of certain enzymes
• Skin biopsy
• Gene testing

BRITTLE CORNEA EHLERS-DANLOS SYNDROME (bcEDS)

Brittle Cornea Ehlers-Danlos Syndrome is presented by thinning of the cornea which may be get ruptured after a minor injury. This disease affects the connective tissue present in the eyes, ears, joints, and skins. It is further divided into two types: brittle cornea syndrome type 1 is caused by a mutation in ZNF469 and brittle cornea syndrome type 2 is caused by a mutation in the PRDM5 gene.

Symptoms Of Brittle Cornea Ehlers-Danlos Syndrome

• Thinning of cornea
• Myopia
• Retinal detachment
• Scoliosis
• Hip dislocation
• Hearing loss

Diagnosis Of Brittle Cornea Ehlers-Danlos Syndrome

The diagnosis of Brittle cornea Ehlers-Danlos Syndrome is based on the physical examination of signs and symptoms.

• Physical examination of eyes, ears, joints, and skin
• Genetic testing

SPONDYLODYSPLASTIC EHLERS-DANLOS SYNDROME (spEDS)

Spondylodysplastic Ehlers-Danlos Syndrome is presented by short stature, translucent skin, bowing of legs, sparse scalp hairs, and eyebrows. It is caused by defects in B4GALT7, B3GALT6, and SLC39A13. The first two genes encodes for the protein that adds galactose to the chain of connective tissue related proteins called proteoglycans. The third one gene encodes for the protein that regulated the uptake of zinc ions into the cells. Abnormality of these protein weaken the connective tissue.

Symptoms of Spondylodysplastic Ehlers-Danlos Syndrome

• Translucent skin
• Sparse scalp hairs
• Hypermobility of joints
• Flat feet
• Low bone density

Diagnosis of Spondylodysplastic Ehlers-Danlos Syndrome

Diagnosis of Spondylodysplastic Ehlers-Danlos Syndrome is based on the physical examination of the patient and results of some tests.

• Urine test
• X-ray
• Genetic testing

MUSCULOCONTRACTURAL EHLERS-DANLOS SYNDROME (mcEDS)

Musculocontractural Ehlers-Danlos Syndrome is presented by congenital malformation, contracture of thumbs and feet, and facial clefting. It is caused by a mutation in the CHST14 gene. This gene is encoded for the enzyme involved in the important complements of the extracellular matrix. When this enzyme is absent the structure of the extracellular matrix becomes weak and results in the symptoms of Musculocontractural Ehlers-Danlos Syndrome.

Symptoms of Musculocontractural Ehlers-Danlos Syndrome

• Club foot
• Inward thumb
• Long and spidery fingers
• Cleft palate
• Hypotonia

Diagnosis of Musculocontractural Ehlers-Danlos Syndrome

The diagnosis of Musculocontractural Ehlers-Danlos Syndrome is based on physical examination, family history, and clinical signs.

• Gene testing
• Molecular testing

 MYOPATHIC EHLERS-DANKOS SYNDROME (mEDS)

Myopathic Ehlers-Danlos Syndrome is presented by large contractures, tightening of muscles, and hypermobility of joints. Is caused by mutation in COL12A1 gene. COL12A1 gene is responsible for formation of type 12 collagen. Type 12 collagen a required of structural integrity and proper functioning of skeleton muscles.

Symptoms of Myopathic Ehlers-Danlos Syndrome

• Atropoc scarring
• Myopathy
• Hypermobikity of joint
• Permanent tightening of muscle
• Large contractures

Diagnosis of Myopathic Ehlers-Danlos Syndrome

Myopathic Ehlers-Danlos Syndrome is difficult to diagnose with the help of clinical signs and a SMTMP that’s why following test are performed to confirm the diagnosis:

• Genetic testing
• Whole-exome sequencing

PERIODONTAL EHLERS DANLOS SYNDROME (pEDS)

Periodontal Ehlers-Danlos Syndrome is presented by severe gums inflammation which eventually ends in loss of teeth. It is the rarest type of Ehlers-Danlos Syndrome. The genetic mutation associated with this type of Ehlers-Danlos Syndrome is still unknown. The onset of Periodontal Ehlers-Danlos Syndrome is early in puberty and the patient loss teeth before the age of 30 years. It is found that some changes in chromosome number 12 are associated with this type but exact gene mutation is not known.

Symptoms of Periodontal Ehlers-Danlos Syndrome

• Short stature
• Periodontitis
• Hyperpigmentation
• Atrophic scars
• Gum overgrowth
• Smaller teeth
• Hyperflexible joints
• Hyperextensibility of skin

Diagnosis of Periodontal Ehlers-Danlos Syndrome

As no genetic cause is known that results in the symptoms of Periodontal Ehlers-Danlos Syndrome so the diagnosis is made on the basis of clinical signs and symptoms and family history.

CONCLUSION

Ehlers-Danlos Syndrome is a group of connective tissue disorders cause by the mutation in Genes. In most cases, Ehlers-Danlos Syndrome is inherited but sometimes it is acquired. Hypermobility of joints, hyperextensibility of skin, and tissue fragility are the key features of patients with Ehlers-Danlos Syndrome. Diagnosis of Ehlers-Danlos Syndromes mostly made by genetic testing and examining the signs and symptoms of the patient.