Marfan Syndrome Q87.4 – Symptoms and Treatment

Disease Definition. Causes of the Disease

Marfan Syndrome (Marfan; SM) is a genetically inherited condition characterized by systemic involvement of connective tissue.

Causes of Marfan Syndrome

The etiology of the disease is a mutation in the FBN1 gene (fibrillin 1), located on the short arm of chromosome fifteen at locus 21.1. Inheritance pattern of the syndrome is autosomal dominant. The disease is characterized by high penetrance (frequency of gene occurrence) and variable expressivity. The ratio of males to females affected is equal.

Symptoms of Marfan Syndrome

The disease shows continuously progressive development. Newborns exhibit elongated thin fingers on both upper and lower limbs and elongated thin extremities (dolichostenomelia). In addition to dolichostenomelia, such patients also show:
• Increased physical development;
• Low weight;
• Elongated skull;
• Elongated face;
• Arachnodactyly (abnormally elongated narrow fingers);
• Weakness and underdevelopment of the muscular system and adipose tissue;
• Awkward movements.

The skin has increased elasticity, loose joints. Most patients have a high arched palate, changes in chest shape (funnel-shaped, keeled), and spinal deformities (scoliosis in 60%, kyphosis, juvenile osteochondrosis), flattening of the foot arch, auscultatory signs of heart defects (murmurs). The length of the third finger of the hand is 10 cm or more (screening test in children aged 7-18 years): the ratio of upper limb span to body length increases.

Signs of Marfan syndrome

Ophthalmological symptoms (nearsightedness, lens subluxation in 75% of cases, its roundness or hypoplasia, retinal detachment) and asthenic signs (fatigue, lethargy) become noticeable from the second year of life, changes in chest shape appear after the age of four, and heart and vascular pathology is detected in preschool age. Almost all patients have heart and aortic defects. Hip and inguinal hernias are common, as well as valve lesions in veins, varicose vein expansion, hemorrhagic syndrome, recurrent dislocations, lung system involvement (spontaneous pneumothorax, emphysematous lung expansion), kidney prolapse.

A person with Marfan syndrome

In a quarter of cases, intellectual impairment is recorded, and half of the patients have disorders of the emotional-volitional sphere. Depressive states, neurocirculatory dystonia often occur. According to many studies, the absolute majority of patients with Marfan syndrome report worsening of emotional background, loss of joy and enthusiasm for professional activities, frequent mood swings, increased excitability, and feelings of anxiety. This results in reduced social activity, deterioration in quality of life, and significant decrease in social adaptation. Patients often have tracheobronchial dyskinesia (respiratory system disorder) due to weakness of the bronchial connective tissue frame. This manifests as recurrent inflammatory diseases of the bronchopulmonary system, obstructive disorders, bronchial asthma, pulmonary emphysema (increased air content in lung tissue). Complications include accumulation of air in the chest, accompanied by compression of the lungs and mediastinum (central area of the chest), subcutaneous emphysema. There is an inadequate response to bronchodilators. Obstructive phenomena (blockage) predominantly affect the upper respiratory tract.

Characteristic changes on the electrocardiogram are described, including early ventricular excitation syndrome, premature ventricular complexes, instability of the terminal part of the ventricular complex in the lower posterior leads. Rhythm pathology most often manifests as right bundle branch block or mixed extrasystole. Patients with Marfan syndrome with rhythm and conduction abnormalities often have autonomic dysfunction syndrome of the vagotonic type, in the form of presyncopal, syncopal, and asthenovegetative states, painful sensations in the heart area, tension headache, often accompanied by psychopathological disorders. The digestive organs are also involved in the pathological process, manifested by dyskinesia (motor impairment) of the biliary tract with decreased smooth muscle motor function, cardia insufficiency, hernial protrusions of the esophageal hiatus, anomalies of the bile ducts, dolichosigmoid (enlargement of the sigmoid colon), chronic gastroduodenitis (inflammation of the gastric and duodenal mucosa), dysbiosis (disruption of normal intestinal flora), changes in the pancreas.

Aortic defect

Patients with Marfan syndrome more often than healthy individuals have acquired kidney anomalies: increased kidney mobility, nephroptosis (kidney prolapse), pyelocalyceal dilatation (abnormal dilation of renal calyces), increased incidence of kidney duplication.”

Pathogenesis of Marfan Syndrome

More than half of a person’s weight is represented by connective tissue, which comprises our main support – the skeleton, and outer coverings – the skin. Blood vessels, blood, and lymph also consist of connective tissue. Connective tissue cells include fibroblasts and their varieties (osteoblasts, chondrocytes, odontoblasts, keratoblasts), macrophages (histiocytes), and adipose cells (lipocytes).

Mesenchyme is the conductor of the constitutional, genetic, and epigenetic components of human life. Pathology of connective tissue determines a specific pathological effect on the entire organism as a whole, its physiology, and its constitutional characteristics.

In Marfan syndrome, there is a substitution of nucleotides in the gene containing information about the structure of the peptide of fibrillin-1. This protein belongs to glycoproteins, participates in the microfibrillar complex, and provides the basis for elastic fibrils of connective tissue.

The extracellular matrix allows connective tissue to maintain a constant structure, containing a huge number of growth factors that ensure constant cell renewal.

Large blood vessels, ligamentous apparatus contain a large number of elastin fibrils, the damage of which gives the main clinical manifestations of Marfan syndrome.

In Marfan syndrome, the transforming growth factor beta (TGF-β) is significantly affected, its binding to its inactive form is disrupted, leading to increased bioactivity of this factor, which is associated with the appearance of many manifestations of the disease.

Disorder of elastic fibrils of connective tissue

Fibrillin pathology leads to fiber formation abnormalities, causing loss of strength and elasticity of the skin and other connective tissue structures.

Changes in the structure of collagen fibers lead to disruption of the primary hemostasis link in patients with Marfan syndrome.

There is evidence of defects in the membrane and cytoplasmic signaling mechanisms directly within the platelet, leading to aggregation disorders. The presence of an independent membrane defect of platelets with disruption of release and transport reactions of intracellular calcium has been shown.

Elastic fibrils have well-defined mechanisms of participation in the hemostasis system. In vessels with low shear rates, platelet adhesion (“sticking”) to elastin occurs through fibronectin. Its level is reduced in the blood of people with Marfan syndrome. Fibronectin, in turn, is formed in endothelial cells and participates in subsequent reparative processes, creating the basis for the production of other components of connective tissue – fibroblasts. Thus, the involvement of the vascular wall in blood clotting reactions is indisputable, and the inevitable conclusion is possible pathologies of the normal hemostatic processes when changing the state of its structural components and processes of vascular regulation.

The role of hormonal imbalance in the development and exacerbation of defects in connective tissue structures has been noted.

Thrombotic manifestations are determined by a violation of blood rheology (viscosity) in pathologically tortuous vessels of the brachiocephalic zone.

Damage to the gastrointestinal tract is determined by the fact that this system is rich in collagen. Biliary dyskinesia of the hypomotor type, hernias of the esophageal hiatus, anomalies of the biliary tract, dolichosigma, chronic gastroduodenitis with a blurred clinical picture and a tendency to a torpid course are observed.

Classification and Stages of Marfan Syndrome Development:

International Statistical Classification of Diseases and Related Health Problems (ICD-10) Code for Marfan Syndrome: Q87.4.

  1. Mild (involvement of no more than two systems, changes are minor).
  2. Severe (minor changes in three systems or significant involvement of one or more systems).

Different severity types are distinguished:

  • Mild
  • Moderate
  • Severe

The frequency of severe forms is 1 in 25,000-50,000 (with an overall frequency of diagnosed cases of 1 in 10,000-15,000).

According to the course:

  • Progressive form
  • Stable form

Often, the first signs of Marfan syndrome manifest in childhood, with symptoms progressing with age and clinical manifestations intensifying.

Complications of Marfan Syndrome:

The most common complications of Marfan syndrome include:

  • Decreased vision, up to blindness, due to weakness of the ciliary zonule (zonule of Zinn) and dislocation or subluxation of the lens.
  • Congestive heart failure due to impaired contractility of the heart muscle and mitral valve insufficiency.
  • Rupture of large blood vessels associated with dilation and thinning of the vessel wall. Aortic involvement is most common (mainly due to changes in hemodynamics during pregnancy).
  • Aortic dissection aneurysm leading to death in patients.
Lens luxation

Diagnosis of Marfan syndrome involves:

  1. Clinical data and identification of changes in the FBN1 gene.
  2. Family history, often revealing cases among relatives with concealed disease progression.
  3. Methods for detecting arachnodactyly, such as the Steinberg and Walker-Murdoch signs, and determination of the metacarpal index using radiography.
  4. International Ghent criteria, which consider the family history. If absent:
  • Aorta diameter enlargement > 2 Z-scores + lens ectopia = Marfan syndrome (MFS).
  • Aorta diameter enlargement > 2 Z-scores + identified FBN1 gene changes = MFS.
  • Aorta diameter enlargement > 2 Z-scores + > 7 systemic features = MFS.
  • Lens ectopia + identified FBN1 gene changes + aortic dilation = MFS.

In the presence of a family history:

  • Lens ectopia + a case of MFS in the family = MFS.
  • > 7 systemic features + a case of MFS in the family = MFS.
  • Aorta diameter enlargement > 2 Z-scores + a case of MFS in the family = MFS.

Additionally, an ophthalmologist consultation is essential upon the slightest suspicion of Marfan syndrome. Urine analysis may show elevated levels of certain compounds, but these are nonspecific and can occur in various connective tissue disorders. The diagnosis is confirmed by assessing systemic signs of connective tissue involvement.


Treatment of Marfan syndrome is primarily symptomatic, aimed at preventing the progression of major clinical manifestations. There is no etiological treatment available.

  1. Physical Activity: Vigorous physical activities are prohibited. Strengthening massages and therapeutic exercises are recommended from infancy.
  2. Orthopedic Correction: Adequate physical activity and orthopedic correction are advised according to professional orientation.
  3. Diet: Diets providing increased intake of proteins, vitamins, micronutrients, and fatty acids are recommended.
  4. Medication: Adaptogens, sedatives, and vegetotropic drugs may be used. Stimulating collagen formation and correcting the synthesis of glycosaminoglycans are crucial. L-carnitine, vitamins B (1, 2, 6), E, C, folic acid, and microelement supplements are utilized.
  5. Ocular Disorders Correction: Eye diseases are corrected surgically.
  6. Treatment of Aortic Aneurysm: Cardiac and vascular pathologies require surgical correction. Beta-blockers are used to prevent significant aortic aneurysm development.
  7. Sanatorium Treatment: It includes relaxing-toning back massages, balneotherapy, carbon dioxide-sulfide baths, mud therapy on affected muscles and spine, high-frequency therapy on pain zones, introduction of antispasmodics and microelements using electrophoresis, local treatment with ultrasound, and diadynamic therapeutic stimulation of weakened muscles.
  8. Physiotherapy: Physiotherapy focuses on strengthening the shoulder girdle and back muscles. Some exercises are performed lying down to avoid spinal overload.
  9. Specialized Sanatorium Complexes: Offered by experts for neurocirculatory dystonia and neuroses, which often accompany Marfan syndrome.
  10. Monitoring and Early Intervention: Verification of coagulation abnormalities in young patients with Marfan syndrome should be done at early stages. Therapeutic measures to manage and prevent hemorrhagic conditions are essential components of comprehensive treatment for children with any connective tissue dysplasia.

The prognosis is generally favorable, but it depends on the extent of cardiovascular and pulmonary involvement. Disability often arises from ocular pathology, while the most common cause of death is vascular and cardiac complications. With proper management and timely intervention, complications are rare. The risk of passing on the condition to offspring is 50%.

Life Expectancy with Marfan Syndrome:

The average life expectancy of patients has significantly increased over the past decades, from around 48 years in 1972 to 72 years in 1993. This trend continues to improve due to advancements in diagnostics, beta-blocker therapy, and preventive aortic root surgery.

Prevention of Marfan Syndrome:
Preventive measures include prenatal and preimplantation diagnostics. Prenatal diagnosis relies on identifying mutations in parents, and invasive procedures such as amniocentesis or chorionic villus sampling are used to collect samples for testing. Preimplantation diagnosis is conducted during in vitro fertilization (IVF) procedures.