Marfan's disease: causes, symptoms and treatment

The disease (syndrome) of Marfan is a hereditary pathology of connective tissue. Since connective tissue is the basis of various human organs, the manifestations of the disease are also very diverse. The most typical are the abnormalities of the cardiovascular system, the musculoskeletal system and the eyes. Diagnosis of Marfan syndrome requires the use of a variety of methods. Treatment includes medical and surgical methods, and the patient should be observed by several doctors. From this article you can learn about the causes, symptoms, diagnosis and treatment options for this disease.

Marfan's syndrome is formed even in the prenatal period, the child is born with already existing disorders. This is perhaps the most common hereditary pathology of connective tissue. Regardless of sex and race, the incidence of Marfan's disease ranges from 1: , 00 to: , 00 people (according to various sources).

Causes

The basis of the disease is a genetic defect: a mutation of the gene responsible for the synthesis of the protein of the connective tissue of fibrillin. The gene is located on the 15th chromosome.

The disease is inherited in an autosomal dominant type. Autosomal means that it is not related to the sex, and the dominant one is that the mutation is always manifested. The degree of manifestation (the prevalence of disorders and their severity) can vary in different limits, which is associated with genetic features.

Fibrillin imparts elasticity and extensibility to connective tissue. Violation of its structure leads to loss of strength and elasticity of connective tissue, and it ceases to serve as a strong framework. First of all, the changes concern the walls of the vessels, the ligamentous apparatus. Even small physiological loads become prohibitive for the body, the connective tissue can not withstand them.

All cases of Marfan's syndrome from the point of view of the cause are divided into:

• family: account for 75%, this is a gene mutation that is passed on from generation to generation;
• random (sporadic): 25%, this is the first emerging mutation of a gene in a genus that has not previously had a similar pathology.

Symptoms

There are a lot of clinical manifestations of the disease. They are considered from the point of view of the defeat of certain organs and systems:

• musculoskeletal system;
• of cardio-vascular system;
• the organ of vision;
• nervous system;
• bronchopulmonary system;
• skin, soft tissues;
• other organs.

Musculoskeletal system

For patients with pathology of connective tissue, hypermobility of the joints is characteristic.

Patients with Marfan syndrome usually have high growth, are thin due to underdevelopment of subcutaneous fat. The body at the same time seems short, and the limbs - disproportionately long. The swing of the arms is more than 5% or more. Skull elongated (dolichocephalic), long arachnid fingers (arachnodactyly). The face is elongated, narrow, the sky is high arched (gothic), the ears are large, the lower jaw protrudes forward (incorrect bite), the teeth grow incorrectly, the eyes are deeply planted.

Deformation of the skeleton consists in the presence of a funnel-shaped or keeled chest, any changes in the spine axis (excess lordosis, kyphosis, kyphoscoliosis, scoliosis), subluxations of the vertebrae (especially in the cervical spine), spondylolisthesis (displacement of the overlying vertebra in relation to the underlying vertebra). Typically, the flat feet of various degrees of severity, loose joints, excessive movements in them (for example, hyperextension), protrusion of the acetabulum (deepening with deep immersion of the head of the femur in the region of the hip joint). Usually all this is accompanied by a decrease in muscle tone.

The cardiovascular system

Changes in this system are often the most difficult, requiring correction in the first place, since they can have a life-threatening character.

Most often, Marfan syndrome is manifested by the presence of malformations of the heart and large vessels (in particular, the aorta). Defects in the structure of the heart are the violation of the partitions of the heart and its valves (prolapse of the mitral valve, defect of the interventricular or interatrial septum, pathological lengthening of the chords). Violation of the structure of the aortic wall leads to the development of its dilatation (expansion) and delamination of the walls (exfoliating aortic aneurysm). From congenital malformations of large vessels can be observed coarctation of the aorta, stenosis (narrowing) of the pulmonary artery.

The pathological structure of the heart and blood vessels is accompanied by the development of heart failure, a violation of the cardiac rhythm (supraventricular and ventricular tachycardia, atrial fibrillation and others), which is very dangerous for life patient. Accession of infectious complications is fraught with the development of infective endocarditis.

Body of sight

Symptoms of eye damage are very specific for this disease. The defeat of the musculoskeletal system, cardiovascular system and the eyes form a typical triad of symptoms in Marfan's disease.

Patients with Marfan syndrome often have blue sclera. Vision is poor due to the development of myopia of a high degree, the length of the eyeball is increased. Pupils may not be symmetrical, that is, different in size. However, this damage to the organ of vision is not limited. Developed strabismus, dislocation or subluxation of the lens, underdevelopment of the iris and ciliary muscles, flattening of the cornea. It is possible to detach the retina with the development of blindness.

Nervous system

The defeat of the nervous system is mainly associated with the pathology of the structure of the vessel wall. This leads to a violation of blood circulation, the development of ischemic or hemorrhagic strokes (more often - subarachnoid hemorrhages).

Frequent fainting is possible. From anomalies, ectasia of the dura mater is possible, in particular, the lumbosacral meningocele (protrusion of the membranes of the brain under the skin with the formation of a pocket through a defect in the vertebrae).

Deviations in psychomotor development are possible, both in the direction of delay and in the direction of exceeding the indices. Many people with Marfan syndrome have high intelligence (higher than the average IQ in the population).

Another symptom of Marfan's disease can be pituitary disorders with an increase in adrenaline in the blood, the development of acromegaly and diabetes insipidus.

Bronchopulmonary system

The defeat of the bronchi and lungs is the development of spontaneous pneumothorax, respiratory failure, emphysema, apical bulbs (blister-like formations in the apex of the lungs). All these changes are the result of a violation of angioarchitectonics of the lungs due to pathology of connective tissue, increased extensibility and reduced elasticity of lung tissue.

Lesion of the skin and soft tissues

Often patients with Marfan syndrome have atrophic striae on the skin: wavy bands on skin of different widths and colors (from white to reddish-violet). A small amount of subcutaneous adipose tissue causes a low weight of such patients.

Patients with Marfan syndrome suffer from recurrent inguinal and femoral hernias.

Other bodies

The pathology of connective tissue becomes the cause of the omission of the kidneys, bladder and uterus, varicose veins widening, leads to the formation of a long and weak intestinal peristalsis (which is accompanied by constipations).

Diagnostics

The doctor may suspect the presence of Marfan syndrome in the patient as a result of examination and examination.

Diagnosis of Marfan's syndrome requires the consideration of anamnestic data (including hereditary history), patient examination data, and carrying out a variety of additional research methods that can detect changes in the heart, blood vessels, brain, lungs, eyes. For this, ECG, Echocardiography (ultrasound of the heart), chest and hip radiography joints, CT or MRI of the brain and spinal cord, heart and blood vessels, ophthalmoscopy, aortography and others methods. The list of studies depends on the presence of symptoms in a particular patient.

There are diagnostic criteria for this disease: large and small. A certain combination of large and small criteria and allows you to confirm the diagnosis. To great criteria, for example, include a subluxation of the lens, ectasia of the dura mater, keel or funnel-shaped chest, flat feet, protrusion of the acetabulum, and others. Small criteria include excessive mobility in the joints, Gothic skies, deformities of the skull, spontaneous pneumothorax and others.

The final diagnosis is made after applying the molecular genetic method and establishing the mutation of the gene responsible for the synthesis of fibrillin.

Treatment

Treatment of the Marfan syndrome always requires the simultaneous participation of several specialists: a cardiologist, a cardiac surgeon, an ophthalmologist, an orthopedist traumatologist, a therapist.

The spectrum of medical procedures covers conservative and operative methods of treatment. Conservative measures are aimed at preventing complications and maintaining the normal functioning of organs and systems, and operational suggest the correction of existing anatomical changes in order to prevent a pronounced impairment of functions or even a threat to life patient.

Surgical methods of treatment:

• reconstructive operations on the aorta (at a significant, more than 5 cm, the expansion of the ascending part of the aorta and the dissection of its wall);
• prosthetics of heart valves;
• removal of the altered lens with its replacement by an artificial one;
• plasticity of the spine in severe scoliosis;
• arthroplasty of the hip joints;
• plastic of the chest (in recent years, its rationale is denied).

The patient needs a selection of glasses or contact lenses, sometimes laser correction of vision is possible.

Medicamental treatment has a pathogenetic and symptomatic orientation. Patients with metabolic goals are prescribed large doses of vitamin C (1-3 g per day), drugs with glucosamine sulfates and chondroitin sulfates (Teraflex, Structum, Chondroxide, Glucosamine, Aminoarthrin, Elbona, Unium), Carnitine chloride 20% solution, Succinic acid is 100-200 mg 2 times a day, magnesium preparations (for example, Magne B6), multivitamin-mineral complexes (with calcium, magnesium, zinc, copper). The intake of these substances is aimed at normalizing the metabolism, strengthening the connective tissue.

To treat cardiovascular disorders, β-blockers are often used (Propranolol, Obsidan, Atenolol), calcium blockers (Nifedipine, Amlodipine, Lecoptin), angiotensin-converting enzyme inhibitors (lisinopril, Perindopril, Enalapril), antiarrhythmic drugs (in case of violation rhythm of the heart). When developing infectious endocarditis, antibiotics are indicated. After surgery, you may need anticoagulant therapy to reduce blood clotting (Fraksiparin, Kleksan).

In general, the selection of the method of treatment and the range of medications used are very individual. It all depends on the spectrum of clinical symptoms and the severity of disorders in a particular patient.

Patients with Marfan's syndrome are shown exercise therapy, but in strictly dosage amounts, so that the exercises benefit the cardiovascular and musculoskeletal systems, and not harm. You can not engage in contact and play sports (basketball, football), recommended swimming.

Forecast

The disease is incurable, but constant dynamic observation of the patient, surgical correction of cardiovascular, joint and ophthalmologic disorders can reduce the risk to life, improve its quality, allow profession. Some patients do not survive to 40 years, which is associated with cardiovascular complications, in others cases, life expectancy is 70 years (especially after cardiosurgical operations).

Thus, the syndrome or Marfan's disease is a hereditary disease, the course of which largely depends on the thoroughness of medical supervision and the timeliness of the provision of medical care. Usually, treatment requires the involvement of many specialists, but such an integrated approach avoids many complications and improves the patient's quality of life.