Marfan Disease (Syndrome)

What is Marfan’s Disease (Syndrome)?

Marfan disease (Marfan syndrome) is a congenital collagenopathy or systemic failure of the connective tissue, characterized by a specific type of inheritance and severe clinical symptoms: manifestations of skeletal, cardiovascular and ocular pathology. Patients with Marfan syndrome have in their history of aortic aneurysm, gigantism, myopia, dolichostenome and arachnodactyly, chest deformity, acetabular protrusion, lens ectopia, flatfoot, ectasia of the dura mater, kyphoscoliosis.

The disease was named in honor of the French pediatrician Antoine Marfan, who for the first time in 1886 described a five-year-old girl with long, thin legs and spider-like fingers.

The ratio of the prevalence of this congenital disease is approximately 1:10 000 people and depends little on gender. However, the percentage among children and adolescents reaches 6.8%, we note that most of them are boys.

Causes of Marfan’s Disease (Syndrome)

Marfan syndrome is a congenital anomaly inherited in an autosomal dominant manner. The cause of the syndrome is the mutation of the FBN1 gene, which is responsible for the synthesis of fibrillin, an intercellular matrix structural protein that provides elasticity and contractility of the connective tissue. Anomaly and lack of fibrillin provoke violations of the formation of fibrous structures and loss of strength and elasticity of the connective tissue, the inability to withstand physiological loads. Histological changes occur in the walls of the elastic type vessels. In 75% of cases, Marfan syndrome has a familial type of inheritance, and in 25% there is a primary mutation. If the father is over 35 years old and there is Marfan syndrome in his history, then there is a very high probability that he will transmit the disease to the child.

Pathogenesis during Marfan’s Disease (Syndrome)

Scientists identify several forms of Marfan syndrome, which depend on the number of affected organs and systems:

  • erased – has weakly expressed changes in 1-2 systems;
  • pronounced – has weakly expressed changes in 3 systems; or marked changes at least in the 1st system; or pronounced changes in 2-3 systems and more.

In Marfan syndrome, the severity of changes is divided into mild, moderate and severe. By the nature of the flow, they distinguish progressive and stable Marfan syndrome.

Symptoms of Marfan’s Disease (Syndrome)

Clinical symptoms of the disease are divided into several groups that reflect the exact localization of manifestations of connective tissue (mesenchymal) dysplasia:

  • osteo-articular disorders (asthenic constitution, narrow facial skull with birdlike facial expression, flat-footedness, narrow and deformed, keeled or funnel-shaped chest, arachnodactyly of the hands and feet, kyphoscoliotic spinal deformity, hypermobility of joints and tendons). Most patients suffer from osteo-articular disorders;
  • changes in soft tissue (low body weight, muscle hypotonia, hypoplasia of adipose tissue and muscles, flat feet);
  • changes in internal organs (ascending aortic aneurysm, valvular prolapses, especially mitral valve prolapse, hypoplastic, expansion of the aortic root and pulmonary artery, aneurysm of the Valsalva sinuses, “drooping”, “dropping” heart, lung lobe reduction, too long and hypoplastic intestine);
  • disturbances in the vision system (blue sclera, high-grade hyperopia, aniridia, severe myopia, ectopia and subluxation of the lens, aphakia, coloboma);
  • disorders of the central nervous system (anisocoria, nystagmus, asymmetry of tendon reflexes, pyramidal disorders);
  • disorders of the pituitary-adrenal system (high growth, acromegaloid disorders, diabetes insipidus, arachnodactylia, elongated limbs, enlarged feet, autonomic disorders);
  • disorders of the cardiovascular system (disorders of intraventricular conduction, moderate signs of left ventricular and atrial myocardial hypertrophy, changes in the heart and great vessels, aortic insufficiency, mitral valve prolapse, impaired intracardiac hemodynamics, aortic root enlargement, aortic bicuspid valve, mitral insufficiency, which is associated with the development of myxomatous degeneration of the valves, an increase in their area, expansion of the fibrous ring, lengthening of the chords, “loosening” of the leaflet and to an increase in prolapse). Patients observed muscle weakness and decreased activity during exercise.

Diagnosis of Marfan’s Disease (Syndrome)

The diagnosis of Marfan syndrome is based on family history, severity of symptoms, physical examination, results of functional, x-ray, ophthalmological and genetic studies, ECG and EchoCG and laboratory studies.

During the diagnosis, phenotypic diagnostic tests are taken into account, which determine the ratio of the hand and height, the length of the middle finger, Varga physique index, the arachnodactyly thumb test, and the wrist coverage test.

ECG determines cardiac arrhythmias, marked myocardial hypertrophy.

EchoCG reveals aortic dilatation, valvular regurgitation, mitral valve prolapse, an increase in the size of the left ventricle, ruptures of the chords.

Chest X-ray allows you to see the expansion of the aortic arch and root, increasing the size of the heart; radiography of the hip joints shows protrusion of the acetabulum

CT and MRI of the heart and vessels are done in order to detect dilatation and aortic aneurysm; An MRI scan of the spine shows ectasia of the dura mater.

Aortography is performed if aneurysm and aortic dissection is suspected.

Biomicroscopy and ophthalmoscopy show ectopia of the lens.

Genetic identification shows changes (mutations) in the FBN1 gene.

In Marfan syndrome, differential diagnosis is used with diseases similar to the syndrome. These include: cytocystinuria, congenital contractual arachnodactyly (Beals syndrome), hereditary arthroophthalmopathy (Stickler syndrome), MASS syndrome, Ehlers-Danlos syndrome, Lois-D syndrome, Lois-D syndrome, Lois-D syndrome, Loesen-D syndrome, EASS-Dallos syndrome Goldberg, family ectopia of the lens, etc.

Treatment of Marfan’s Disease (Syndrome)

The treatment of Marfan syndrome includes conservative and surgical correction of cardiovascular disorders, skeletal lesions and organs of vision.

The treatment is primarily aimed at preventing the development of the disease and complications in the cardiovascular system. If the aorta diameter is up to 4 cm, the patient is prescribed calcium antagonists, β-blockers or ACE inhibitors. Surgical intervention is performed only when the aortic diameter is more than 5 cm with mitral valve prolapse, heart valve insufficiency, ascending part and aortic dissection.

In Marfan syndrome, reconstructive operations are performed on the aorta. If necessary, performed mitral valve replacement.

Patients with Marfan syndrome are prescribed vision correction by the method of selecting glasses and contact lenses, and in difficult cases by laser or surgical treatment of eye diseases.

Children with skeletal disorders are subjected to surgical stabilization of the spine, hip arthroplasty, thoracoplasty.

The course of treatment includes: vitamin therapy, pathogenetic collagen-normalizing and metabolic therapy.

Prevention of Marfan’s Disease (Syndrome)

Patients with this syndrome are under constant medical supervision, they regularly undergo diagnostic examination. Children are allowed to exercise lightly, excluding sports competitions, scuba diving, contact sports.

The profile is timely cardiac surgery correction, which increases the life expectancy up to 70 years.