Ehlers-Danlos syndrome

Ehlers-Danlos syndrome is associated with deformities in connective tissue.

 

Some rarer types of Ehlers-Danlos disease can be lethal, leading to the rupture of arteries.

Lifestyle modifications are commonly recommended with minimal evidence regarding their effects.

Aggressive blood pressure control and heart rate is the cornerstone management vascular Ehlers-Danlos syndrome.

Each type of Ehlers-Danlos syndrome  is caused by a different mutation. 

The  vascular type of this disorder is caused by a mutation in collagen type 3.

Associated with hyperextensible skin, bleeding tendency associated with berry aneurysms and hypermobility of joints.

Estimated 1 in 10,000 to 1 in 15,000 worldwide.

Among the most common genetic connective tissue disease to cause intractable pain.

Known as the hypermobility syndrome.

Associated with angioid streaks.

Patients can displace their extremities out of their joints.

Associated with progressive deterioration of connective tissue in joints, spine, eye, gums, teeth, internal organs and CNS.

Ehlers-Danlos syndromes are a group of genetic connective tissue disorders.

Symptoms may include loose joints, stretchy skin, and abnormal scar formation.

The disease process can be noticed at birth or in early childhood.

Complications include: aortic dissection, joint dislocations, scoliosis, chronic pain, or early osteoarthritis.

Differential diagnosis: Marfan syndrome, cutis laxa syndrome, familial joint hypermobility syndrome.

Frequency 1 in 5,000 births worldwide.

Due to a mutation in one of more than a dozen different genes, which determines the specific form of disease.

A new mutation can occur during early development.

In other cases E-D Sx is inherited in an autosomal dominant or recessive manner.

These mutations result in defects in the structure or processing of collagen.

The diagnosis is confirmed with genetic testing or a skin biopsy.

Hypochondriasis, depression, or chronic fatigue syndrome may occur.

Treatment is supportive in nature as no cure is available.

Physical therapy and bracing may help strengthen muscles and support joints.

Some disorders result in a normal life expectancy.

Ehlers-Danlos Syndrome types that affect blood vessels generally result in a shorter life expectancy.

Affects about one in 5,000 people.

The prognosis depends on the specific disorder.

Signs and symptoms vary widely based on the specific type EDS the patient has.

Affects connective tissues, most typically in the joints, skin, and blood vessels.

Findings range from mildly loose joints to life-threatening complications.

Unstable hyperflexible joints are prone to sprain, dislocation, subluxation, and hyperextension causing musculoskeletal symptoms.

Patients have early onset of advanced osteoarthritis, swan-neck deformity of the fingers, and Boutonniere deformity of the fingers.

May be associated with tearing of tendons or muscles.

Spine changes such as scoliosis, kyphosis, tethered spinal cord syndrome, and occipitoatlantoaxial hypermobility may also be present.

Patients may experience myalgia and arthralgia.

Trendelenburg’s sign, occurs commonly: when standing on one leg, the pelvis drops on the other side.

Osgood-Schlatter disease is common.

Infants may have delayed walking to up to 18 months of age and may manifest with bottom-shuffling instead of crawling.

The weak connective tissue causes fragile skin that tears easily, atrophic “cigarette paper” scars, easy bruising. redundant skin folds, and Molluscoid pseudotumors on pressure points, livedo reticularis, and piezogenic papules are less common..

In vascular EDS, thin, translucent, and extremely fragile skin that tears easily is also a symptom.

Heart conduction abnormalities have been found in those with hypermobility form of EDS.

A carotid-cavernous sinus fistula occurs in 10% of patients, resulting in sudden blurred vision and ocular pain requiring rapid intervention.

Skin fragility import wound healing our findings.

Dilation and/or rupture of ascending aorta aneurysm has been reported, as has postural orthostatic tachycardia syndrome, Raynaud’s phenomenon, varicose veins, heart murmur, gastrointestinal reflux, celiac disease, Gorlin’s sign touching tongue to nose, anal prolapse, spontaneous pneumothorax, carpal tunnel syndrome, neuropathy, Arnold-Chiari formation, platelet aggregation failure, pregnancy complicationwithincreased pain, mild to moderate peripartum bleeding, cervical insufficiency, uterine tearing, or premature rupture of membranes,

The pain associated with the disorders may be severe.

Normal collagen fibrils are of uniform size and spacing.

Collagen provides structure and strength to connective tissue, and a defect can weaken connective tissue in the skin, bones, blood vessels, and organs, resulting in the features of the disorder.

Patients with classical EDS show composite fibrils.

Mutations in these genes usually alter the structure, production, or processing of collagen or proteins that interact with collagen.

Fibrous proteins: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, and TNXB

Enzymes: ADAMTS2, PLOD1, B4GALT7, DSE, and D4ST1/CHST14

Most forms of EDSs are inherited in an autosomal dominant pattern, which means only one of the two copies of the gene in question must be altered to cause a disorder.

Some cases are inherited in an autosomal recessive pattern, which means both copies of the gene must be altered for a person to be affected.

Sporadic mutations also occur.

Diagnosis can be established by medical history and clinical observation.

The Beighton criteria can be used to assess the degree of joint hypermobility.

DNA and biochemical studies can help identify affected patients: collagen gene-mutation testing, collagen typing via skin biopsy, echocardiogram, and lysyl hydroxylase or oxidase activity.

Tests are not able to confirm all cases.

Evaluation by a geneticist remains essential.

Prenatal diagnosis may be possible using a DNA information technique known as a linkage study.

Hypermobile EDS is characterized primarily by joint hypermobility affecting both large and small joints, which may lead to recurrent joint dislocations and subluxations.

Hypermobile EDS patients have soft, smooth, and velvety skin with easy bruising and chronic pain of the muscles and/or bones.

No genetic test for this type is available for hypermobile EDS.

Classical EDS is associated with extremely elastic, smooth skin that is fragile and bruises easily, atrophic scars and joint hypermobility.

Calcified hematomas over pressure points such as the elbow and fat-containing cysts on forearms and shins are also frequently seen.

Vascular EDS (type 4 vEDS) is characterized by thin, translucent skin that is extremely fragile and bruises easily.

In vascular EDS arteries and certain organs such as the intestines and uterus are also fragile and prone to rupture.

People with vascular EDS typically have short stature, and thin scalp hair, large eyes, an undersized chin, sunken cheeks, a thin nose and lips, and ears without lobes.

In vascular EDS joint hypermobility is present, but generally confined to the small joints.

Other common features of vascular EDS include club foot, tendon and/or muscle rupture, premature aging of the skin of the hands and feet, early onset varicose veins, pneumothorax, recession of the gums, and a decreased amount of fat under the skin.

Vascular EDS can be caused by the mutations in the COL3A1 gene.

Kyphoscoliosis EDS or type 6 kEDS is associated with hypotonia at birth, delayed motor development, progressive scoliosis and scleral fragility.

Kyphoscoliosis EDS affected people may also have easy bruising, fragile arteries that are prone to rupture, unusually small corneas, osteopenia, marfanoid habitus.

Kyphoscoliosis EDS can be caused by mutations in the gene PLOD1.

Arthrochalasia EDS (types 7A & B aEDS) is characterized by severe joint hypermobility and congenital hip dislocation, fragile, elastic skin with easy bruising, hypotonia, kyphoscoliosis, and mild osteopenia.

In Arthrochalasia EDS type-I collagen is usually affected, and mutations in the genes COL1A1 and C

Classical-like EDS (type 1 cEDS) is characterized by skin hyperextensibility with velvety skin texture and absence of atrophic scarring, generalized joint hypermobility with or without recurrent dislocations and easily bruised skin or spontaneous ecchymoses.

Dislocations occur most often in the shoulder and ankle.

Spondylodysplastic EDS (spEDS) is characterized by short stature, muscle hypotonia and bowing of limbs.

Musculocontractural EDS (mcEDS) is characterized by congenital multiple contractures, characteristically adduction-flexion contractures and/or clubfoot, characteristic craniofacial features, which are evident at birth or in early infancy, and skin features such as skin hyperextensibility, bruising, skin fragility with atrophic scars, and increased palmar wrinkling.

Myopathic EDS (mEDS) is characterized by congenital muscle hypotonia and/or muscle atrophy that improves with age, proximal joint contractures and hypermobility of distal joints.

Periodontal EDS (pEDS) is characterized by severe and intractable periodontitis of early onset, lack of attached gingiva, pretibial plaques, and family history of a first-degree relative who meets clinical criteria.

Cardiac-valvular EDS (cvEDS) is characterized by severe progressive cardiac-valvular problems of the aortic valve, mitral valve, hyperextensibility of skin, atrophic scars, thin skin, easy bruising, and joint hypermobility.

The classification system for EDS included 10 specific types, and also acknowledged that other extremely rare types existed, but the present classification is limited to 6 major types, of which hypermobility (type 3), the most common.

Some specific mutations involved can be precisely identified by genetic testing.

Negative genetic test results do not rule out the diagnosis, since not all of the mutations have been discovered.

Differential diagnosis

Cutis laxative; loose skin, hanging, and wrinkled.

Marfan’s syndrome: mobile joints and similar cardiovascular

Loeys-Dietz syndrome

Fibromyalgia

Menke’s disease

Pseudoxanthoma elasticum (PXE)

As no cure is available treatment is supportive.

Monitoring of the cardiovascular system, physiotherapy, occupational therapy, to help strengthen muscles and to teach people how to properly use and preserve their joints. wheelchairs, bracing, casting, stabilizing the joints and preventing injury.

Avoiding activities that cause the joint to lock or overextend.

Aquatic therapy increases muscular development and coordination.

Manual therapy mobilizes the joints within the range of motion.

Medical intervention is limited to symptomatic therapy.

Instability of almost all joints can occur, but most often in the lower and upper extremities, with the wrist, fingers, shoulder, knee, hip, and ankle being most common.

Surgical joint repair may be necessary, including joint debridement, tendon replacements, capsulorraphy, and arthroplasty.

It is felt conservative treatment is more effective than surgery, particularly since patients have extra risks of surgical complications due to the disease: strength of the tissues is decreased, fragility of the blood vessels and wound healing is often delayed or incomplete.

Surgery management requires careful tissue handling and a longer immobilization periods.

The use of local anesthetics, arterial catheters, and central venous catheters cause a higher risk in haematoma formation in people with an EDS.

Patients show a resistance to local anaesthetics.

The outlook with EDS depends on the specific type of EDS they have, and symptoms and complications vary in severity as well.

Some people have negligible symptoms.

Other patients are severely restricted in daily life, with joint instability, chronic musculoskeletal pain, degenerative joint disease, frequent injuries, and spinal deformities.

Most patients have a normal lifespan.

Patients with blood-vessel fragility have a high risk of fatal complications, including spontaneous arterial rupture.

Patients with blood vessel frigidity are at risk for sudden death.

The median life expectancy in the population with vascular ED is 48 years.

The average age of onset of the first major arterial or gastrointestinal complication is about 31 years.

Approximately 15% of patients have intestinal perforation, usually in the sigmoid colon.

The most prevalent is hypermobile EDS, followed by classical EDS.

The others types are very rare.

Some EDSs are more common in Ashkenazi Jews.

Patients with severest forms of the disease seldom live past 50 years.

As connective tissue deteriorates, painful microtears affect organs and cause severe pain, essentially from head to toe.

Patients may become bedridden.

Patients may experience catastrophic events, such as cerebellar herniation, spinal cord tethering, adhesive arachnoiditis, aortic rupture, cerebral vascular rupture, uterine rupture and

In patients with G.I. symptoms 39% presented with constipation and 3% and rectocele.