Marfan syndrome - Causes, symptoms and treatment. MF.

Marfan syndrome refers to monogenic connective tissue diseases - a group of nosological forms of different origin that combine hereditary connective tissue dysfunction. Most of this pathology is caused by the violation of enzyme systems that control the synthesis of structural proteins from which the synthesis of connective tissue occurs. Almost all of these diseases, which are part of the syndrome, lead to severe disabling disorders.

Marfan syndrome was first described by Williams in 1876. The name of the disease was obtained from the French pediatrician Marfan, who observed a girl with a characteristic symptomatic complex of the disease 20 years later. There is an interesting fact that the first model girl - Leslie Hornby, who served as the prototype of the image of all models, had the Marfan syndrome. Thus, it has been established that a number of world-famous people suffered from Marfan syndrome, among them one should mention the US President A. Lincoln and the great violinist Paganini.

Leslie Hornby( Twiggy)

Symptoms of Marfan syndrome

The clinical picture of the disease is characterized by the defeat of many vital organs and systems: the musculoskeletal system, cardiovascular system, respiratory and vision organs, CNS.

So, among the constitutional features and disorders of the skeleton, the most common are the dolichoplastic( asthenic) type, high growth( usually above 180 cm) with a pronounced body mass deficit( usually below 50 kg), arachnodactyly( "spider" fingers) of the hands and feet, kyphoscoliosis, funnel-shaped or keel-like deformations of the thorax, flat feet, narrow facial skeleton, "gothic" sky. Not necessarily in one person there are all these signs, these are only the most common

Arachnodactyly

Appearance of a patient with Marfan's syndrome

An antimonogloidal incision of the eyes, a "large" nose, large low ears, a "bird's" facial expression are also typical. In newborns of the above features of the skeleton, as a rule, only the dolichoplastic type and arachnodactyly are detected. The remaining symptoms are formed in later periods of development( usually during the first seven years of life of the child).

The defeat of the heart and blood vessels is one of the cardinal signs of the Marfan syndrome. The most typical of them are prolapse of the mitral valve and aortic aneurysm. Cardiovascular disorders are registered already in the first-second years of the child's life, with a gradual increase in the diameter of the aorta, reaching critical dimensions( up to 6 cm and more), more often between the ages of 16 and 45 years.

A formidable complication of the aortic aneurysm is the dissection of its walls, which can quickly progress, capturing the entire length of the aorta and the vessels that leave it. Such complications, as a rule, end lethal.

The bronchopulmonary system is also involved in the pathological process in the Marfan syndrome. A prerequisite for this is the mechanical compression of the respiratory tract with deformations of the chest and changes in connective tissue structures of the lung tissue. Respiratory disorders in the form of spontaneous pneumothorax, pulmonary emphysema, pulmonary infarction occur at a frequency of 10 to 75%.Along with this, there is information about the congenital maldevelopment of one of the lobes of the lung, polycystic lungs, congenital bullous emphysema, bilateral bronchiectasis.

The most typical pathology of the organ of vision in Marfan's syndrome is the dislocation and subluxation of the lens( due to the weakness of the zinn ligament).As a rule, this pathology is combined with myopia or hypermetropia of a high degree. Subluxation of the lens is usually diagnosed at 1-5 years of life, and sometimes even at 7 years old when the child is enrolled in school. Less common secondary glaucoma, cataract, detachment of the retina. These changes are more often detected in patients older than 15-40 years.

IQ( coefficient of intellectual development) in most children with Marfan syndrome usually corresponds to the norm - 85-115 units. There are people with very high intelligence, in which IQ exceeds the upper limit of the norm -115 units. However, there may be a certain specificity of mental processes, which manifests itself in uneven intellectual activity, as well as in the personal characteristics of patients( irritability, tearfulness, excessive self-esteem).

All children with Marfan syndrome are characterized by low tolerance of exercise, which is often accompanied by pain in the muscles. There are also periodic attacks of migraine-like headache, which, as a rule, occurs against the background or after emotional and physical exertion. These signs of the disease, combined with weakness, hypotension and hypoplasia of the muscle tissue, as well as disabilities of physical development indicators, are evidence of a change in the function of mitochondria( a violation of cellular bioenergetics).

Diagnosis of Marfan syndrome

Diagnosis of Marfan syndrome is based on genealogical data( the compilation and analysis of pedigrees) and the analysis of the morphophenotype, which includes the study of the physical, neuropsychic development of children and the state of the physical development of patients is carried out using Stewart's percentile scales.

The proportionality or harmony of individual body parts is judged by using the Du Rant-Layner index, which is calculated by the formula A / B x 100, where A is the ratio of the actual body weight to the 50th percentile of the mass corresponding to the patient's growth, and B is the ratio of the actual length of the bodyto the 50th percentile of the corresponding age. The index quantitatively reflects the variations of physical development. At the same time, the figure of 89 and below corresponds to high growth with a body weight deficit, indices - 110-119 - excessive body weight, over 120 - obesity. For children over 120 - obesity. For children with Marfan syndrome, the Du Rant-Liner index is usually 51-81.

According to the resolution of the meeting on Marfan syndrome, at least one of the five main symptoms of the disease( lens dislocation, aortic aneurysm, arachnodactyly, sternal deformity, kyphoscoliosis) and two additional symptoms( myopia, mitral valve prolapse, moderate hyperplasticity of joints, highgrowth, flat feet, striae, pneumothorax).

It is established that in 90% of all cases of Marfan syndrome, difficulties in establishing the correct diagnosis, as a rule, do not arise. However, in 10% - diagnosis is difficult. In such situations, an extremely thorough examination of the maximum number of relatives of the patient is especially necessary. The survey program for such families must necessarily include consultative, examinations of the oculist, cardiologist and echocardiography.

In the diagnosis of Marfan syndrome, the results of X-ray and functional methods of investigation are also widely used. Thus, metacarpal index( length-to-width ratio of the second-fifth metacarpal bones), calculated from the radiograph of the right hand, is used to assess arachnodactyly. In patients with Marfan syndrome, an increase in this indicator to 8.0-11.0 at a rate of 6.4-7.9 is observed.

The nature and severity of the cardiovascular pathology is assessed by echocardiography, ECG, Holter monitoring. The analysis of the bronchopulmonary system is carried out according to the results of the study of the function of external respiration. The overwhelming number of children with Marfan syndrome are registered changes in these parameters manifested in the violation of the mechanics of breathing, swelling of the lung tissue, uneven distribution in the lungs of inhaled air of hypercapnia. In children with Marfan's syndrome, a decrease in the reparative capacity of DNA lymphocytes is detected, which should be taken into account when choosing a profession and the place of residence of patients with an X-ray examination.

In Marfan syndrome, there is an increase( twice or more) of urinary excretion of gicosaminoglycans and their fractions, with a particularly marked increase in renal excretion of chondroitin-4-6-sulfates and, to a lesser extent, hyaluronic acid and heparin sulfate.

Differential diagnosis is performed with similar syndromes and genetic diseases. As a criterion of comparison is a number of signs of manifestation of various diseases.

Signs

	various syndromes with similar symptoms
Marfan	Beals	Stickler	Weill-Marchezani
asthenic constitution	+	+	+	-
arachnodactyly	+	+	+	-
deformation thorax	+/-	+ /-	-	-
aortic aneurysm	+	-	-	-
subluxation lens	+	-	-	+/-
Autosomal dominant inheritance	+	+	+	-

syndrome TreatmentMarfan

Children with Marfan syndrome are shown complex therapy, which includes a wide range of medicines - drugs that affect the cardiovascular system, CNS stimulants, energy metabolism drugs and antioxidants according to the scheme "Complex of therapeutic effects used to treat patients with Marfan syndrome"

Beta-adrenoblockers- obzidan, atenolol - 10 mg / day, duration 6-12 months or more.

Energotropic and antioxidant preparations:
1. Riboxin - 1 tab.(0.2) 2 times a day for 1 month, 3 courses per year;
2. vitamins B1 B2 - 10 mg / day, 10 days monthly;
3. ascorbic acid up to 500 mg / day, for 1 month, 3-4 courses per year;
4. tocopherol( vit E) to 100 mg / day, for 3-4-month courses per year;
5. Elcar - 200-400 mg / day, 3 months, 2-3 courses per year;
6. Dimefosfon - 30 mg / kg - 1 month, 3-4 courses a year, • coenzyme Q10 - 30 mg 2-3 times a day, 3 months, 2-3 courses per year,
7. limonar - 5 mg /kg / day, 10 days, 4 courses per year,
8. nootropic preparations of piracetam -200-400 mg 2 times a day for 2 months, 3 courses per year

Along with medicines, children with Marfan syndrome also need a set of additional(10 courses, 3 courses per year), electrosleep( the course of 10 sessions - twice a year), physiotherapy exercises with a predominant effect on the support-d(a course of 14 days, 4 courses a year), a sanatorium for patients with impaired functions of bones and joints or the cardiovascular system( treatment course 24 days - once a year) but indications, surgical treatment of thoracoplasty, aneurismectomy, aortic plasty, lens extraction, tonsillectomy and adenotomy. A regular sanation( at least twice a year) of chronic foci of infection of the mouth and teeth is also carried out.

Under the influence of complex therapy, 78-80% of children with Marfan syndrome have an improvement or stabilization of the underlying pathological process.

Clinical criteria for the effectiveness of the treatment are increased tolerance to physical activity, increased muscle strength, stabilization of the diameter of the aorta( according to echocardiography) and the tendency to normalize the function of external respiration, improve fine motor skills, increase emotional tone, increase the amount of random memory and concentration,increase in school performance. Positive biochemical dynamics is manifested in a decrease in the level of lactic and pyruvic acids.

When observing patients with Marfan syndrome, the following requirements for work, rest and rehabilitation should be met:

1. children with Marfan's syndrome are allowed to exercise only on a weakened program( special groups and groups of exercise therapy);
2. It is strictly forbidden to practice in sports sections, participate in competitions, agricultural work, long-distance trips over rough and mountainous terrain, heavy loads( no more than 3 kg);
3. Specialties associated with occupational hazards are strictly forbidden: contacts with chemicals, varnishes, paints, work in conditions of high temperatures and exposure to radiation, as well as occupations associated with vibration, requiring high visual acuity, great physical and emotional costs;
4. when choosing a place of residence, patients are adversely affected by the hot climate and high radiation areas;
5. Pregnant women with Marfan syndrome should have an echocardiogram once every 2 months. With aorta diameter of 45 mm and above, the question of the advisability of further pregnancy maintenance should be resolved without delay;
6. The delivery of women with Marfan syndrome should be performed with caesarean section in specialized maternity hospitals for women with cardiovascular pathology.

Prevention of Marfan syndrome

Patients with Marfan's syndrome who are getting married are shown medical genetic counseling, information on the degree of repeated risk of developing a similar disease in children. Along with this, pre-natal diagnosis is also necessary.

Doctor therapist Zhumagaziev E.N.