Diagnostics of the Marfan syndrome

There are 3 simple and accurate signs for the detection of arachnodactyly.

• The sign of 1 finger, or the symptom of Steinberg (Steinberg), - 1 finger protrudes from the hypotenar with a clenched fist.
• The sign of the wrist, or the Walker-Murdoch symptom, is the entry of one finger for the little finger when the hand is grasped in the area of the wrist joint of the other hand.
• Fifth index (radiologic sign) - the average length of the pastern, divided by the average width of the segment from the 2nd to the 4th metacarpal bone, is normally 5,4-7,9, and for SM - more than 8,4.

Diagnosis of Morfan syndrome is based on international Ghent criteria, adopted by a group of experts. The algorithm is based on the allocation of large and small criteria that characterize the severity of changes in connective tissue in organs and systems. Large criteria indicate the presence of pathologically significant changes in the relevant organ system, small criteria - about the involvement of a particular system in pathology. The requirements for the diagnosis of Morphan syndrome differ depending on the data of the hereditary anamnesis.

For the patient being examined:

• if the family or hereditary history is not burdened, Morfan syndrome is established in the presence of large criteria in at least two different organ systems and the involvement of the third system;
• in the case of a mutation that is known to cause Morphan's syndrome in others, one large criterion is sufficient in one organ system and the involvement of the second system.

Ghent criteria for the diagnosis of Marfan syndrome (De Raere A. Et al., 1996)

Great criteria (signs)	Small criteria (signs)
Skeletal-skeletal
Four of the eight:	Arched palate with hocking of teeth
Kyloid deformity of the thorax;	Moderate funnel-shaped deformation of the chest
Funnel-shaped deformation of the chest, requiring surgical intervention;	Hypermobility of the joints
The ratio of the upper and lower segments of the body <0.89 or the ratio between the range of arms and length of the body> 1.03;	Deformation of the skull (dolichocephaly, hypoplasia of the zygomatic bones, enophthalmosis, oblique downward glottis, retrognathia)
Positive finger and wrist tests;
Scoliosis> 20 'or spondylolisthesis;
Reduced elbow elongation up to 170 * or less;
The medial displacement of the medial malleolus, leading to flat feet;
protrusion of the acetabulum of any degree (confirmed radiologically)
Changes in the osteoarticular system correspond to a large criterion if at least 4 of the above 8 large signs are identified. The osteoarticular system is involved if at least 2 large signs or 1 large and 2 small signs are identified
System of the organs of vision
Subluxation of the lens	Abnormally flat cornea (according to keratometry results)
	Increased axial length of the eyeball (according to ultrasound measurements) with myopia
	Hypoplasia of the iris or hypoplasia of the ciliary muscle causing miosis
The visual system is involved if two small criteria are identified
The cardiovascular system
Expansion of the ascending aorta with or without regurgitation and involvement of at least sinuses of Valsalva; or Ascending aortic dissection	Mitral valve prolapse Expansion of the pulmonary artery in the absence of valvular or peripheral pulmonary stenosis or any other obvious cause at the age younger than 40 years Calcification of the mitral ring at the age younger than 40 years Expansion or stratification of the wall of the thoracic or abdominal aorta at the age younger than 50 years
The cardiovascular system is involved if one large and one small criteria are identified
Respiratory system
None	Spontaneous pneumothorax, or
	Apical bullae, confirmed by a roentgenogram of the chest
The pulmonary system is involved if one small criterion
Leather
None	Atrophic striae, not associated with pronounced changes in body weight, pregnancy, or frequent local mechanical effects
	Recurrent or postoperative hernia
Skin is involved if one small test is detected
Dura mater
Lumbar-sacral dural ectasia, revealed on CT or MRI	None
Family and hereditary history
The presence of close relatives who independently meet these diagnostic criteria	None
The presence of a mutation in the FBN1 gene
The presence among DNA relatives of markers SM
Involvement in the presence of 1 large criterion

For persons in relationship with a patient who has Morphan syndrome diagnosed, a sufficiently large criterion in the family history, as well as one large criterion in one organ system and involvement of another system.

In 15% of cases, Morphan syndrome cases are sporadic, parents may have erased symptoms, the incidence of the disease increases with the father's age of more than 50 years. In the families of patients, GI diseases, vegetative and vertebrogenic disorders, eye diseases are frequent. If Morphan's syndrome is suspected, an ophthalmological examination is mandatory. In the urine of patients, the increased content of hydroxyproline, glycosaminoglycans is determined, these indices are nonspecific and occur in all disorders of connective tissue exchange, with the excretion of hydroxyproline reflecting the severity of the disease. The aggregation function of platelets is disrupted. The prolapse of the mitral valve is met in most patients, with Morfan syndrome, more often than in the case of a primary mitral valve prolapse, a deflection, an increase in the size of the valves and violation of the chords are revealed.

Differential diagnosis is carried out with diseases that have a marfanoid phenotype. In addition to the Morfan syndrome, the authors of the Ghent criteria singled out hereditary conditions that are phenotypically similar to it.

• Hereditary contracture arachnodactyly (OMIM 121050).
• Family aneurysm of the thoracic aorta (OMIM 607086).
• Hereditary stratification of the aortic wall (OMIM 132900).
• Hereditary ectopia of the lens (OMIM 129600).
• Family marfanoid appearance (OMIM 154750).
• MASS-phenotype (OMIM 604308).
• Syndrome of hereditary prolapse of the mitral valve (OMIM 157700).
• Syndrome of the Stickler (hereditary progressive arthro-ophthalmopathy, OMIM 108300).
• The syndrome of the Spritzen-Goldberg (marfanoid syndrome with craniosynostosis, OMIM 182212).
• Homocystinuria (OMIM 236200).
• Ehlers-Danlo syndrome (kyphoscoliotic type, OMIM 225400; hypermobile type, OMIM 130020).
• Syndrome of hypermobility of joints (OMIM 147900).

All these hereditary connective tissue disorders have common clinical features with Morfan syndrome, so a strict attitude is so important to the criteria of diagnosis. Given the complexity of molecular genetic studies, the diagnosis of Morphan's syndrome and the above-mentioned syndromes, which have a number of common phenotypic manifestations, remains, first of all, a clinical task. If the patient lacks 2 large criteria in 2 systems and signs of third involvement, the diagnosis of Morfan syndrome can not be made.

Among the above-mentioned close to Syndrome Morfan syndromes are particularly common and belong in the group NDST marfan-like appearance, MASS-phenotype, joint hypermobility syndrome and hereditary mitral valve prolapse syndrome.

[1], [2], [3], [4], [5], [6], [7], [8]