Ehlers Danlos Syndrome

In the classic type, the skin is hyperelastic, fragile and smooth and velvety to touch. Skin is prone to rupturing even after minor trauma. The joints are hyperextendable. Joint dislocations are common. Wound healing is impaired. Other signs and symptoms include:

• Hypotonia and delayed motor development
• Fatigue
• Cramps
• Easy bruising
• Spontaneous vessel ruptures
• Valvular prolapse
• Atrophic scars

In hypermobility type, grotesque contortions are seen, such as bending the thumb backwards to touch the forearm or bending the knee almost at a right angle. Chronic pain, joint dislocations and joint hypermobility are other manifestations. Bowel disorders might also be seen.

The vascular type manifests as

• Thin skin
• Arterial or uterine rupture
• Bruising
• Small joint hyperextensibility

In kyphoscoliosis type, the manifestations are:

• Hypotonia
• Joint laxity
• Congenital scoliosis
• Ocular fragility

In arthrochalasia variant, the following findings are present.

• Severe joint hypermobility
• Mild skin changes
• Scoliosis
• Bruising

The dermatosparaxis type shows up as:

• Severe skin fragility
• Cutis laxa
• Bruising

The clinical evaluation and family history are important diagnostic tools. The qualitative and quantitative analysis, sequencing and biochemical testing can establish the type of Ehlers Danlos syndrome present in the patients. Deletion and duplication testing can also be done to pinpoint the mutations that have occurred. Prenatal diagnosis pre implantation genetic diagnosis (PGD) for at-risk pregnancies can also be done.

Conservative treatment of Ehlers Danlos syndrome is possible with the following:

• Braces for joint support to prevent dislocation
• Appropriate therapy for gastritis/reflux /delayed gastric emptying/irritable bowel syndrome
• Beta-blockers for progressive aortic enlargement
• Analgesics for chronic pain
• Pain-oriented counseling
• Exercise to improve muscle tone [8]
• Calcium and vitamin D supplements to increase bone density
• Echocardiogram for pregnant women with known aortic root dilation.
• Genetic counseling

Symptomatic treatment of bone, gastrointestinal, dental, and hematologic manifestation should be done accordingly [9] [10].

The surgical treatment is delayed in favor of physiotherapy for as long as possible. Long-term improvement in shoulder stability with Achilles tendon allograft reconstruction of the joint capsule has been reported.

The prognosis is poor for the patients suffering from the vascular variety of Ehlers Danlos syndrome. Complications leading to morbidity and sudden death are often seen.

Prognosis is better for the other types of Ehlers Danlos syndrome, although there is reduced quality of life.

Based on the clinical and molecular patterns, Ehlers Danlos syndrome has been subdivided into six clinical forms.

Classical

Genes other than those coding for collagen have been hypothesized to be involved in the classical type of Ehlers Danlos syndrome. In 30 to 50% of these cases, mutations in the genes COL5A1 AND COL5A2 that encode type V collagen have been observed [4] [5]. It is autosomal dominant.

Hypermobility

It is also an autosomal dominant disorder. The gene involved in its causation has not been detected as yet.

Vascular

An autosomal dominant disorder, the vascular type arises due to the mutations in COL31A gene encoding the type III collagen [6].

Kyphoscoliosis

Inherited as an autosomal recessive trait, kyphoscoliosis type arises due to the mutations in the genes encoding lysyl hydroxylase, an enzyme responsible for hydroxylation of lysine residues during collagen synthesis.

Arthrochalasia

Having an autosomal dominant pattern of inheritance, the arthrochalasia variant of Ehlers Danlos syndrome arises due to the mutations in COL1A1 or COL1A2 genes, resulting in formation of structurally abnormal pro α 1 or pro α 2 chains that resist cleavage of N-terminal peptides, a crucial step in type I collagen synthesis.

Dermatosparaxis

It is an autosomal recessive disorder, caused by defect in the conversion of procollagen to collagen.

Being a genetic disorder, the incidence of Ehlers Danlos syndromes, worldwide is 1:5,000 people worldwide. The hypermobility and classical variants are more common. Hypermobility Ehlers Danlos syndrome affects 1 in 10,000 to 15,000 while classical type occurs in as many as 1 in 20,000 to 40,000 people worldwide. Other forms of Ehlers Danlos syndrome are even rarer.

The disease is equally prevalent in all races. Ehlers Danlos syndrome is inherited in autosomal pattern [7]. It occurs without the involvement of sex chromosomes, therefore both sexes are equally affected. Although present at birth, it becomes apparent much later.

Median life expectancy for patients with vascular type Ehlers Danlos syndrome is 50 years. Average life span of patients with Ehlers Danlos syndrome is 50 years. Only the spontaneous rupturing of vessels and intestines can pose life threatening risks. Uterine rupture during pregnancy can also endanger maternal and neonatal life.

Collagen is an integral part of the connective tissue. Faulty synthesis and functioning can give rise to hyperextensibility of the skin. As a result, grotesque deformities arise. Joint dislocations become common. Skin becomes lax and prone to injuries.

Collagen deficiency in arterial wall causes thinning of vascular walls which can rupture spontaneously. Being a part of scar tissue, fault in the laying down of scars after injury can lead to delayed wound healing and easy bruising even after minor injuries.

Type I collagen is present in muscles. Its deficiency leads to impairment of motor functions and difficulty in starting and carrying out the movements (hypotonia). Cramps, easy fatigability and malaise ensue. Being part of the connective tissue of the valves, deficient and faulty collagen can also lead to dysfunction of the valves.

The vitreous humor of eye also contains collagen, the deficiency of which can lead to visual disturbances. Being part of the bone and cartilage, deficiency of collagen also induces bony deformities like scoliosis.

Constant surveillance of at risk population with family history of Ehlers Danlos syndrome should be done as a primary preventive measure. Resistance exercise can increase muscle tone. High impact activities should be avoided. Crutches, canes, and walkers should be used but with caution, as they tend to exert pressure on the upper extremities.

Secondary interventions, like calcium and vitamin D supplementation should also be done.

Ehlers Danlos syndromes are a genetically inherited, heterogeneous group of disorders that arise due to abnormality of collagen fibers [1]. There are several different types of Ehlers Danlos syndrome depending upon the type of the abnormality [2][3]. The abnormality may arise in the structure or synthesis of collagen or in the proteins that closely interact with collagen. The defect may also arise in one of the proteins closely associated with collagen, like those taking part in its post transcriptional modification.

Collagen provides basic structural support to the connective tissue and is found in tendons, ligaments, vascular wall, cornea, cartilage, bone, gut, muscles and in the skin in abundance. Therefore, the changes in the structure and functions of collagen can lead to the manifestation of a wide range of clinical symptoms.

Ehlers Danlos syndrome is a syndrome in which anomalies arise in skin and other soft tissues of the body. The basic fault lies in the genetic makeup of the individual therefore, Ehlers Danlos syndrome tends to run in families.

As basic structural support of organs is lost in Ehlers Danlos syndrome, therefore, patient experiences signs such as thin and fragile skin, ability to bend the joints to degrees that are not normally possible, easy dislocation of joints, easy bruising even after minor injuries, bursting of blood vessels, difficulty in starting and maintaining movements, easy fatigability and delayed wound healing.

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7. Araki T, Samejima T, Sako T. [Ehler-Danlos syndrome occurring in a family]. Seikeigeka. Orthopedic surgery. Oct 1966;17(10):822-826.
8. Bathen T, Hangmann AB, Hoff M, Andersen LO, Rand-Hendriksen S. Multidisciplinary treatment of disability in ehlers-danlos syndrome hypermobility type/hypermobility syndrome: A pilot study using a combination of physical and cognitive-behavioral therapy on 12 women. American journal of medical genetics. Part A. Dec 2013;161A(12):3005-3011.
9. Bergqvist D, Bjorck M, Wanhainen A. Treatment of vascular Ehlers-Danlos syndrome: a systematic review. Annals of surgery. Aug 2013;258(2):257-261.
10. Jones ML. Orthodontic treatment in Ehlers-Danlos syndrome. British journal of orthodontics. Jul 1984;11(3):158-162.

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