Ehlers Danlos Syndrome Treatment, Types, Symptoms, Causes: Ehlers-Danlos syndrome is a hereditary systemic connective tissue dysplasia caused by insufficient development of collagen structures. Depending on the clinical type, Ehlers-Danlos syndrome may manifest as hypermobility of the joints, extraordinary vulnerability and stretchability of the skin, a tendency to hemorrhage and bleeding, deformities of the spine and chest, myopia, strabismus, ptosis of internal organs, etc. data, results of skin biopsy and genotyping; possible prenatal diagnosis of pathology. Treatment of Ehlers-Danlos syndrome is reduced to compliance with a gentle regimen, protein diet, symptomatic therapy.
- Causes of Ehlers-Danlos syndrome
- Classification of Ehlers-Danlos syndrome Symptoms of Ehlers-Danlos syndrome
- Diagnosis of Ehlers-Danlos syndrome
- Treatment of Ehlers-Danlos syndrome
- Prognosis of Ehlers-Danlos syndrome
Ehlers-Danlos syndrome (imperfect desmogenesis, hyperelastic skin), along with imperfect osteogenesis , Marfan syndrome and other diseases, belongs to hereditary collagenopathies. Ehlers-Danlos syndrome is heterogeneous and includes a heterogeneous group of hereditary lesions of the connective tissue ( connective tissue dysplasias ) associated with impaired collagen protein biosynthesis. Manifestations of Ehlers-Danlos syndrome are systemic in nature and affect the musculoskeletal system, skin, cardiovascular, visual, dentition and other systems. Therefore, Ehlers-Danlos syndrome is of practical interest not only for genetics, but also for traumatology and orthopedics, dermatology ,cardiology , ophthalmology , dentistry .
The difficulty of verification and the presence of mild forms makes it difficult to obtain accurate information about the true prevalence of Ehlers-Danlos syndrome; the frequency of diagnosed moderate cases is 1: 5 000 newborns, severe forms – 1: 100 000.
Causes of Ehlers-Danlos syndrome
Different variants of Ehlers-Danlos syndrome vary in their inheritance type, primary molecular and biochemical defects. However, all clinical forms are based on gene mutations that cause quantitative or structural pathology of collagen. To date, the molecular mechanisms of Ehlers-Danlos syndrome are not established for all forms of the disease.
So, it is known that type I syndrome is characterized by a decrease in the activity of fibroblasts, increased synthesis of proteoglycans, and the absence of enzymes responsible for normal collagen biosynthesis. Ehlers-Danlos syndrome type IV is associated with insufficiency of type III collagen production; in type VI of the disease, there is a deficiency in the enzyme lysyl hydroxylase, which is involved in the hydroxylation of lysine in procollagen molecules. Type VII is caused by a violation of the conversion of procollagen type I into collagen; X type – pathology of plasma fibronectin, which participates in the organization of the intercellular matrix, etc.
The pathological picture of different types of Ehlers-Danlos syndrome is characterized by thinning of the dermis, disorientation and loss of compactness of collagen fibers, proliferation of elastic fibers, increase in the number of vessels and expansion of their lumen.
Classification of Ehlers-Danlos syndrome
In total, there are 10 types of Ehlers-Danlos syndrome, differing in genetic defect, inheritance and clinical manifestations. Consider the main ones:
- Type I Ehlers-Danlos syndrome (classic severe course) is the most common variant of the disease (43% of cases) with an autosomal dominant mode of inheritance. The leading symptom is the hyperelasticity of the skin, the stretchability of which is 2-2.5 times increased compared with the norm. Characterized by hypermobility of the joints, which is of a generalized nature, skeletal deformities, increased skin vulnerability, a tendency to external bleeding , scarring , poor wound healing. In some patients, the presence of mollusk-like pseudotumors and varicose veins of the lower extremities is detected. Pregnancy in women with type I Ehlers-Danlos syndrome is often complicated by preterm labor .
- Type II Ehlers-Danlos syndrome (classic mild course) – characterized by the above symptoms, but less pronounced. Extensibility of the skin exceeds the normal by only 30%; hypermobility is noted mainly in the joints of the feet and hands; bleeding and scarring tendency are minor.
- Type 3 Ehlers-Danlos syndrome – has autosomal dominant inheritance, benign course. Clinical manifestations include generalized increased joint mobility, musculoskeletal deformities. The remaining manifestations (hyperelasticity and scarring of the skin, hemorrhages) are minimal.
- Type IV Ehlers-Danlos syndrome – is rare, difficult; can be inherited in various ways (dominant or recessive). Hyperelasticity of the skin is negligible, there is an increased mobility of only the joints of the fingers. The leading manifestation of this type of disease is hemorrhagic syndrome: a tendency to the formation of ecchymosis, spontaneous hematomas (including in the internal organs), ruptures of the hollow organs and vessels (including the aorta). Accompanied by high mortality.
- V type of Ehlers-Danlos syndrome – has X-linked recessive inheritance. It is characterized by increased skin stretchability, moderately pronounced joint hypermobility, bleeding and skin visibility.
- Type VI Ehlers-Danlos syndrome is inherited in an autosomal recessive manner. In addition to the hyperelasticity of the skin, the tendency to bleeding, increased mobility of the joints, there is hypotonia, severe kyphoscoliosis , and clubfoot . A characteristic feature of Ehlers-Danlos syndrome type VI is ocular syndrome, manifested by myopia , keratoconus , strabismus , glaucoma , retinal detachment , etc.
- VII type of Ehlers-Danlos syndrome (arthroclasia) – inherited both autosomal dominant and autosomal recessive. The clinical picture is determined by the low growth of patients and the hyper-mobility of the joints, leading to frequent habitual dislocations.
- VIII type of Ehlers-Danlos syndrome is predominantly inherited autosomal dominantly. The fragility of the skin, pronounced periodontitis , leading to the early loss of teeth, plays a leading role in the clinic .
- X type Ehlers-Danlos syndrome – characterized by autosomal recessive inheritance; moderate hyperelasticity of the skin and hypermobility of the joints, stretches (band-shaped atrophy of the skin ), violation of platelet aggregation.
- XI type of Ehlers-Danlos syndrome – has autosomal dominant inheritance. Patients have recurrent dislocations of the shoulder joints , dislocations of the patella , congenital dislocation of the hip .
- Type IX (X-variant of flaccid skin) is currently excluded from the classification of Ehlers-Danlos syndrome. In the modern version of the classification of Ehlers-Danlos syndrome, 7 main types of the disease are considered:
classic (types I and II)
hypermobile (type III)
vascular (type IV)
kyphoscoliosis (type VI)
arthroclasia (type VIIB)
dermosparaxis (type VIIC)
lack of tenascin-X
Symptoms of Ehlers Danlos syndrome
Due to the fact that the detailed description of various types of Ehlers-Danlos syndrome is given above, in this section we summarize the main manifestations of the disease. Since connective tissue is present in almost all organs, the manifestations of Ehlers-Danlos syndrome are systemic, generalized.
Leading to the clinical picture is skin syndrome: skin hyperelasticity, which easily folds and folds. To the touch the skin is velvety, soft, weakly fixed with the underlying tissues, wrinkled on the palmar and plantar surfaces. Hyperelasticity of the skin in Ehlers-Danlos syndrome occurs from birth or preschool age, tends to decrease over the years.
In addition, hyperstretchiness is characterized by increased vulnerability, brittleness of the skin, which is found at the age of 2–3 years. Minimal trauma leads to the formation of non-healing wounds, at the site of which atrophic or keloid scars and pseudotumor form after a while .
The articular manifestations of the Ehlers-Danlos syndrome are represented by hypermobility (looseness) of the joints, which may be local (for example, re-extension of the interphalangeal joints) or generalized. Articular syndrome manifests with the beginning of the baby’s walking, which leads to repeated subluxations and dislocations. With age, joint hypermobility usually decreases.
Since the cardiovascular system in children with Ehlers-Danlos syndrome, congenital heart defects , mitral valve prolapse , cerebral aneurysm , and varicose veins are often detected . There is a tendency to bleeding – ecchymosis, hematomas of various localization, nasal , gingival, uterine , gastrointestinal bleeding .
Eye manifestations of Ehlers-Danlos syndrome may include eyelid hyperelasticity, myopia, ptosis , strabismus, corneal and eyeball ruptures with minimal mechanical damage , spontaneous retinal detachment.
Changes in the skeleton in Ehlers-Danlos syndrome are characterized by funnel-shaped or keeled chest deformity , scoliosis , kyphosis , clubfoot, abnormal bite , partial adentia. Visceral disorders are represented by ptosis of internal organs, umbilical , inguinal , diaphragmatic hernias , recurrent spontaneous pneumothorax , intestinal diverticulosis , etc. The mental development of children with Ehlers-Danlos syndrome usually corresponds to age.
Diagnosis of Ehlers Danlos syndrome
The diagnosis of Ehlers-Danlos syndrome is carried out by a medical geneticist on the basis of genealogical data, anamnesis, clinical analysis, molecular genetic studies. Pre-Ehlers-Danlos syndrome may be suspected if there are large diagnostic criteria (joint hypermobility, skin hyperelasticity, bleeding tendency) and additional minor (fragility of the skin, pathology of the heart, blood vessels, eyes, etc.).
Some forms of the disease require a skin biopsy for histological, histochemical, electron microscopic examination.
The presence of Ehlers-Danlos syndrome in the family is an indication for medical genetic counseling and invasive prenatal diagnosis .
Patients with different types of Ehlers-Danlos syndrome may need to be monitored and examined by a traumatologist-orthopedist , pediatric cardiologist , pediatric ophthalmologist , pediatric dentist , and vascular surgeon .
Treatment of Ehlers Danlos syndrome
Effective specific therapy for Ehlers-Danlos syndrome has not been developed. Children need to create a gentle treatment that eliminates excessive trauma to the joints and skin; limitation of physical activity; protein diet with the inclusion in the diet of bone broths, aspic, jelly. Mandatory regular courses of massage, physical therapy , physiotherapy ( magnetic therapy , electrophoresis , laser puncture ).
Drug therapy of Ehlers-Danlos syndrome includes the use of amino acids (carnitine), vitamins (C, E, D, group B), chondroitin sulfate, glucosamine, mineral complexes (calcium and magnesium preparations), metabolic drugs (riboxin, ATP, coenzyme Q10) repeated courses up to 1-1.5 months. 2-3 times a year.
In Ehlers-Danlos syndrome, surgical treatment can be indicated: reconstruction of the chest wall , removal of pseudo-tumors, correction of CHD, etc.
Prognosis of Ehlers-Danlos syndrome
The quality and duration of life of patients with Ehlers-Danlos syndrome affects the type of disease. The most serious prognosis is type IV syndrome Ehlers-Danlos – death may occur due to ruptures of blood vessels, internal organs and bleeding. The presence of type I syndrome significantly limits the quality of life. The course of the II — III types of the disease is relatively favorable.
In general, the presence of Ehlers-Danlos syndrome is fraught with many social difficulties, limits the full physical activity and choice of profession.