Diagnosis of undifferentiated connective tissue dysplasia

Generally accepted algorithms for diagnosing undifferentiated connective tissue dysplasia are absent. The complexity of diagnosis is exacerbated by the lack of an accurate definition of the nature and quantity (specificity) of the symptoms. The peak of diagnosis is in the senior school age. Prognostic factors of the genealogical anamnesis for the formation of undifferentiated connective tissue dysplasia are signs of DST in relatives of I and II degrees (deformities of the chest, prolapses of the heart valves, hypermobility of the joints, hyperextension and thinning of the skin, spine pathology, myopia). The data of pedigrees testify to the accumulation in the family of pathology related to DST: osteochondrosis, polyarthritis, varicose veins, hernias, hemorrhagic diseases. The presence of hypermobility of the joints can often be established with blood relatives.

Certain combinations of external signs suggest a syndrome or phenotype. The lowest specificity and diagnostic sensitivity are articular hair dryers and hypermobility of the joints, since they can be detected in almost all dysplastic syndromes and phenotypes. Also low specificity have such as myopia, scoliosis and asthenic physique. The greatest diagnostic sensitivity is possessed by skin driers, arachnodactyly, deformations of the thorax. The smallest cardiac anomalies are most closely associated with external and internal DST hair dryers.

Syndrome of hypermobility of the joints is diagnosed with 2 large criteria, 1 large and 2 small, or 4 small criteria. Two small criteria are sufficient if there is a close relative suffering from this disease. Syndrome of hypermobility of joints is excluded in Marfan or Ehlers-Danlo syndromes (except for hypermobile type). Syndrome of hypermobility of joints is a common and benign variant of NDT, on the other hand, it can be a symptom of a more serious and clinically significant disease. When revealing signs of hypermobility syndrome of joints, the presence and severity of bone-skeletal and cutaneous dysplasia dysplasia and signs of involvement of the cardiovascular system and the organs of vision should be assessed.

The revised diagnostic criteria for the benign form of joint hypermobility syndrome (Grahame R. Et al., 2000)

Big criteria

Small criteria

The Beyton score is 4/9 or higher (both at the time of the survey and in the past) Arthralgia 4 or more joints for more than 3 months

Beton's score is 1,2 or 3/9 Arthralgia (> 3 months) in 1 -3 joints or back pain, spondylosis, spondillosis / spondyllisthesis Displacement / subluxation of more than one joint or one joint with repeated repetition Inflammation of soft periarticular tissues. Three or more lesions (eg, epicondylitis, tendosynovitis, bursitis) Marfanoid appearance Skin anomalies: stripes, hyperextension, thin skin, scars formation by the type of tissue paper Signs associated with the organs of vision: epicanth, myopia, antimonogloid eye incision Varicose veins or hernia, prolapse of uterus / rectum

The diagnosis of undifferentiated connective tissue dysplasia, suspected during examination, requires an instrumental examination. Diagnostic signs of DST, detectable during examination:

• cardiovascular system: systolic noise, valve prolapse, aneurysm of the atrial septum and sinuses of the Valsalva, false chords, dystonia of the papillary muscles, enlargement of the root of the aorta;
• system of respiratory organs: tracheobronchial dyskinesia, hyperventilation syndrome, bronchial hyperreactivity;
• system of digestive organs: propensity to inflammatory diseases of the mucous membranes of the stomach and intestines, persistent excesses and deformations of the gallbladder, excessively long hypoplastic intestine, visceroptosis;
• urinary system: nephroptosis, atony of the bowel-and-pelvis system, increased renal mobility, doubling of the kidneys or urinary tract, orthostatic proteinuria, the release of increased amounts of hydroxyproline;
• CNS: thermoregulation disorders, asymmetry of tendon reflexes, pyramidal disorders, Spina bifida, juvenile osteochondrosis;
• musculoskeletal system: instability of the cervical spine, scoliosis of the thoracic and cervical spine, subluxation of the cervical vertebrae, decreased BMD.

For the diagnosis it is expedient to use the criteria of the above 10 dysplastic syndromes and phenotypes.

Marfan-like appearance suggests signs of a predominant involvement of the skeletal system (the presence of four or more bone-skeletal hair driers).

Marfan-like phenotype includes a wide range of states from "incomplete Marfan's syndrome" to relatively lighter conditions, which are diagnosed with signs of involvement of at least 3 systems: bone-skeletal, cardiovascular and at least one of the two - pulmonary or visual. Below is a list of visceral signs:

• Cardiovascular system: dilatation of the aorta, small cardiac abnormalities (except mitral valve prolapse), pulmonary artery enlargement, calcification of the mitral valve;
• pulmonary system: tracheobronchial dyskinesia, spontaneous pneumothorax in the anamnesis;
• system of vision: myopia, abnormally flat cornea.

MASS-phenotype is recognized:

• with prolapse of the mitral valve;
• enlargement of the aorta within 2a;
• skin involvement (hyperextension, striae);
• involvement of the skeletal system.

Primary (isolated) mitral valve prolapse:

• EchoCG-signs of prolapse of the mitral valve, including with myxomatous degeneration of the valves;
• signs of skin involvement, bone-skeletal system and joints;
• no evidence of aortic enlargement.

Eler-like phenotype (classical) includes a wide range of states from "incomplete" SED to very light and clinically less significant conditions, which are diagnosed with signs of skin involvement, muscular system, and vessels.

Ehlers-like hypermobile phenotype:

• hypermobility of joints (up to 4 points in Beiton);
• pain less than 3 months in 1-3 joints, rare subluxations, spondillosis;
• complications of hypermobility (sprains, dislocations and subluxations, flat feet);
• signs of involvement of the skin and / or bone-skeletal system.

Dermatomal hypermobility of joints:

• signs of hypermobility of joints (4 or more points in Beiton);
• there is no arthralgia and involvement of the skeletal system and skin.

Unclassified phenotype of undifferentiated connective tissue dysplasia :

• identify 6 or more of any external DST fenders;
• There is insufficient evidence for the diagnosis of the above dysplastic phenotypes.

Increased dysplastic stigmatization:

• 3-5 external dryers DST;
• different variants of a combination of bone-skeletal, skin and joint hair driers;
• there are no significant small heart anomalies and other visceral signs of DST.

Increased dysplastic stigmatization with predominantly visceral manifestations:

• single external hair dysplasia;
• 3 and more small heart anomalies and / or connective tissue carcass of other internal organs.

Significant differences in the clinical symptoms of individual dysplastic syndromes and phenotypes with different prognostic significance were revealed. Unclassified phenotype and increased dysplastic stigmatization have minimal clinical manifestations of dysplasia and are close to the variants of the norm. Phenotypes 1-4 partially coincide in clinical manifestations with Marfan syndrome, 5-7 with the classical and hypermobile types of SED. In the case of the last three types, one can speak of an unclassified DST. In children, differentiating undifferentiated connective tissue dysplasia by syndromes and phenotypes is somewhat more difficult due to the unfinished formation of organs and systems.

Clinically differentiated and undifferentiated forms can not always be clearly delimited, often the diagnosis is formulated only with the quantitative calculation of characteristics.

The molecular genetic diagnosis of congenital DST is promising. However, most biochemical and molecular genetic methods are time consuming and require expensive equipment. That is why the clinic-anamnestic and functional methods of examination are most accessible for screening examination of children. Such children are often observed by various narrow specialists who prescribe each of their treatment, sometimes untimely and not giving the desired effect. The child is exposed to a lot of diagnoses, thus there is no comprehension of a pathology of an organism as a whole. It is necessary to allocate such patients to a special high-risk group with multiple organ pathology.

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