Symptoms of undifferentiated connective tissue dysplasia

Phenotypic signs of connective tissue dysplasia:

• constitutional features (asthenic physique, lack of mass);
• the actual DST syndrome (abnormalities of the facial skull and skeleton, limbs, including kyphoscoliosis, chest deformity, hypermobility of the joints, hyperelasticity of the skin, flat feet);
• small developmental anomalies, which in themselves have no clinical significance, but act as stigma.

A close relationship between the number of external hair dryers, the degree of severity of external dysplastic disorders and changes in the connective tissue framework of internal organs is established - the internal phenotypic signs of the syndrome.

One of the important signs of undifferentiated connective tissue dysplasia is asthenic physique, its combination with bone deformities, hypermobility of joints is characteristic. They note thinning, hyperelasticity, skin vulnerability, foci of depigmentation and subatrophy. When examining the cardiovascular system, systolic murmur is often detected. In half of patients, heart rhythm disturbances are diagnosed, more often - blockade of the right leg of the fasciculus and extrasystole. In ECG, valve prolapse, aneurysm of the atrial septum and sinuses of the Valsalva, enlargement of the aortic root and so-called small heart anomalies: additional chords in the left ventricular cavity, dystonia of the papillary muscles. The defeat of the heart usually proceeds relatively favorably.

There is a definite relationship between the number, degree of expression of the dysfunctions of undifferentiated connective tissue dysplasia and the number of small heart anomalies. The generalized form of undifferentiated connective tissue dysplasia should be called cases in which it is possible to identify signs of clinically significant involvement in a defect of 3 or more organs and systems.

A frequent combination of the inferiority of connective tissue structures of the heart with deviations in the functioning of the autonomic nervous system was noted. Frequent symptoms are psycho-vegetative disorders: an increased level of anxiety, emotional instability. In children with undifferentiated connective tissue dysplasia with rhythm and conduction disorders, the syndrome of vegetative dysfunction proceeds primarily in the vagotonic type, in the form of syncopal and asthenic conditions, cardialgia, tension headaches and is often accompanied by psychopathological disorders. According to cardiointervalography, almost all children with heart DST have manifestations of vegetative dysregulation, which indicates a decrease in adaptive capacity. As the syndrome of DST grows, changes in personality-characterological features are observed, reflecting an increase in the propensity to mental disadaptation.

Tracheobronchial dyskinesia is recorded in a number of cases due to a violation of the elasticity of the trachea and bronchi, and obstructive syndrome is severe and long-lasting.

The gastrointestinal tract as one of the richest in collagen in DST is involved in the pathological process, which manifests itself in the microdiabetes of the intestine, a violation of the excretion of digestive juices and peristalsis. Virtually all patients with hereditary connective tissue diseases are diagnosed with superficial inflammatory changes in the gastric mucosa, pathological refluxes in combination with Helicobacter colonization, and gastric motility disorder.

From the urinary system, nephroptosis, increased renal mobility, pyeloectasia, kidney doubling, orthostatic proteinuria, increased excretion of hydroxyproline and glycosaminoglycans are of diagnostic importance.

In the clinical picture, hemorrhagic syndrome is noted due to platelet abnormalities, a decrease in the synthesis of von Willebrand factor. Frequent nasal bleeding, petechial-spotted rashes on the skin, bleeding gums, the duration of bleeding with cuts. The development of hemorrhagic syndrome is associated not only with the inferiority of the connective tissue of the vessels, but also with the insufficiency of the contractile apparatus of platelets and is associated with autonomic disorders. These changes are often combined with the development of leuko- and thrombocytopenia, with violations of platelet hemostasis, inferiority of coagulation. Frequent violations of immunological competence due to dystrophic changes in timolymphoid tissue. A large number of foci of chronic infection are characteristic. With DST, patients were found to be addicted to the development of autoimmune processes.

Neurological pathology is detected in the majority of sick children (vertebrobasilar insufficiency against the background of instability or dysplasia of the cervical spine, juvenile osteochondrosis, spina bifida, intracranial hypertension, migraine, thermoregulatory disorders). In children of puberty, there is a transformation of symptoms, the main target organs are the spine and the organ of vision.

The process of unifying medical terminology led to the approval of the term "hypermobile syndrome" as an international term. Although this term does not exhaust the whole variety of combinations of noninflammatory lesions of connective tissue, today it must be recognized as successful. Advantages of the term - allocation of generalized hypermobility of the joints as the most characteristic and easily identifiable clinical sign of this group of diseases, and the absence of the word "joint" in the definition of the physician focuses on extra-articular (systemic) manifestations of the syndrome. An important reason for the international medical community's acceptance of this name was the development of criteria for the diagnosis of hypermobility syndrome and the existence of a simple point system (the Beaton scale), which makes it possible to assess the presence of generalized hypermobility. A standard examination of arthrologic patients (radiography of the affected joint, blood test for acute phase indices) does not reveal any signs of pathology. The key to the diagnosis is the detection of hypermobility of the joints with the exclusion of other rheumatic diseases (the latter is a prerequisite). It must be remembered that a person with hypermobility can develop any other joint disease.

Recognition of generalized hypermobility of joints (Beighton P.)

	Ability	On right	Left
1	Extension of the little finger> 90 '	1	1
2	Bringing the thumb across and back to the contact with the forearm	1	1
3	Retarget elbow joint> 10 "	1	1
4	Overextension of the knee> 10 "	1	1
5	Squeeze the hands to the floor, without bending the knees (1 point)	1

The maximum number of points is 9

The degree of joint mobility has a normal distribution in the population. Hypermobility of joints is noted in about 10% of people, only a small part of them is pathological in nature. The presence of hypermobility can often be established with blood relatives (mostly with similar problems). In 75% of cases, the onset of clinical manifestations is at school age, the most frequent option is arthralgia of the knee joints. The increased amplitude of movements reduces the stability of the joint and increases the frequency of dislocations.

Hypermobility is the result of weakness and stretchiness of ligaments, which are hereditary in nature. Of particular importance in this respect are genes that code for the synthesis of collagen, elastin, fibrillin and tenaskin. Clinical significance is determined by frequent dislocations and subluxations, arthralgia, autonomic dysfunction. Thus, the understanding of the relationship between the hypermobility of the joints and the hypermobility syndrome of the joints is helped by the formula of R. Graham (2000):

Hypermobility of joints + Symptomatology = Syndrome of hypermobility.

With mechanical overload against the background of reduced resistance of cartilage and other connective tissue structures, micronecrosis and inflammation can develop (arthritis with synovitis or bursitis), exercise arthropathy with dysplasia of the osteochondral cartilage apparatus. Most patients suffer from non-inflammatory joint diseases (arthrosis, chronic spine diseases).

Characteristic signs of exercise arthropathy:

• family forms of early osteoarthritis or osteochondrosis;
• presence in the anamnesis of lesions and ruptures of ligaments, joints, subluxations, joint and bone pains;
• communication of pain syndrome with physical activity;
• low activity of inflammation, subsidence of it as the load decreases, rapid pain relief and recovery of movements;
• defeat of one or two joints along the axis;
• limited effusion;
• the presence of local tenderness of the joint;
• presence of osteoporosis, hypermobility of joints and other signs of connective tissue dysplasia.

Still, patients with "blurred" signs of NDT are more likely to meet. Identification of phenotypic signs of NDT in combination with the above manifestations should lead the doctor to the idea of the possibility of a clinically significant systemic defect in connective tissue.

Diagnostic signs of connective tissue dysplasia revealed during examination

Anamnesis	Slow healing of wounds and scars Pain in the joints Pain in the spine Cardialgia Feeling of lack of air Increased fatigue Sinus, nasal bleeding, bleeding in the vascular-platelet type
General inspection	Body length> 95 centile Ratio of arm span to body length> 1.03 Hernias, muscle diastases Asthenic physique Hypoplasia of musculature and adipose tissue
Leather	Atrophic striae, visible vasculature Increased skin extensibility Foci of depigmentation Dark spots Hypertrichosis Hemangiomas, angioectasias Ecchymoses, positive test Dry wrinkled skin Transverse folds on the abdomen
Head	Dolichocephaly, skull asymmetry Long or short neck Abnormalities of the auricles (low position and asymmetry, improper development of curls, small or overgrown earlobes, large, small or protruding ears) High or Gothic palate Splitting of the tongue Anomalies of occlusion Definition of language Disturbed growth of teeth and their anomalies Curvature of nasal septum
Torso	Chest deformity (funnel-shaped, keel-shaped, decrease in anterior-posterior size) Scoliosis due to dysplasia of the ligamentous apparatus Thoracic lordosis
Face	Widely or closely located eyes Short or narrow glottis Pathology of the eye (lens dislocations, keratoconus, anisocoria, blue sclera, coloboma) Chin chin Small or large mouth
Arms	Hypermobility of the joints (overexploitation, positive symptom of the thumb) Long fingers, positive symptoms of the thumb Thickening of nail phalanges, syn-, polydactyly, disturbance of nail growth Short or curled little fingers IV finger shorter than II
Legs	Increased length of foot, flat feet Hypermobility of the joints (overextension of the knee joints, flexion of the foot> 45 ') Vein dilatation, venous valve insufficiency Common dislocations and subluxations of joints Sandal-shaped slit X- and O-shaped curvature of legs

Note. Each hair dryer is evaluated from 0 to 3 points depending on the severity (0-lack of hair dryer, 1 - insignificant, 2 - medium, 3 - significant phenotypic sign). Children with a score of more than 30 have a diagnostically significant set of signs of DST. When calculating, only points scored by objective examination are assessed. The score of more than 50 allows you to think about a differentiated DST.

The most numerous complaints were related to cardiac and autonomic symptoms. Headaches (28.6%), recurrent bronchial obstruction (19.3%), cough (19.3%), difficulty in nasal breathing (17.6%), abdominal pain (16.8% ), rashes on the skin (12.6%), joint pain (10.9%), fatigue (10.9%), subfebrile condition (10.1%).

In the structure of the main diagnoses, the high incidence of allergic diseases detected in 25.2% of children (the majority was bronchial asthma - 18.5% of the group) attracts attention; The second in frequency was neurocirculatory dysfunction - 20.2%. In third place were diseases of the musculoskeletal system and connective tissue, revealed in 15.1% (DST was 10.9% of the group). Diseases of the digestive system were found in 10.1% of children. All children had concomitant diagnoses, the overwhelming majority - more than one. Diseases of the musculoskeletal system and connective tissue were reported in 37.0%, NDST was exhibited in 19.3%, respiratory infections in 27.7%, allergic diseases in 23.5%, gastrointestinal diseases in 20.2% , in the nervous system - in 16.8%.

Features of ECG were revealed in 99.1% (an average of 2.2 ECG phenomena per child). Metabolic disorders in 61.8%, blockade of the legs of the rVica bundle in 39.1%, sinus arrhythmia in 30.1%, ectopic rhythm in 27.3%, displacement of the electric position in 25.5%, early syndrome repolarization of the ventricles - in 24.5%, displacement of the electric axis to the right - in 20.0%. On EchoCG, small heart abnormalities were detected in 98.7% (an average of 1.8 per child). The most frequent anomalies were the presence of chords in the left ventricular cavity (60.0%), the prolapse of the mitral valve of the 1st degree (41.9%), the prolapse of the tricuspid valve of the 1st degree (26.7%), the prolapse of the valves of the pulmonary trunk (10.7% ), Valsalva sinus enlargement (10.7%), which significantly exceeds the population frequency of Echocardiography findings.

With ultrasound of the digestive tract, changes were detected in 37.7% (an average of 0.72 findings on the examined). Deformation of the gallbladder - in 29.0%, additional spleen - in 3.5%, increased echogenicity of the pancreas and the wall of the gallbladder, discololia, hypotension of the gallbladder - by 1.76%, respectively, other changes - 7.9% . With ultrasound of the kidneys, violations were diagnosed in 23.5% of children (an average of 0.59 findings). Hyper-motility of the kidneys was revealed - in 6.1%, pyeloectasia - in 5.2%. Doubling of the bowel-and-pelvic system and nephroptosis - 3.5% each, hydronephrosis - 2.6%, other changes - 7%.

Violations in neurosonography were detected in 39.5% (0.48 of the examined): bilateral dilatation of the lateral ventricles - in 19.8%, their asymmetry - in 13.6%, unilateral dilatation - in 6.2%, other changes in 8.6%. Radiography and ultrasound showed a high incidence of disorders in the cervical spine (81.4%, an average of 1.63 per examined): instability was detected in 46.8%, scoliosis of the cervical spine in 44.1%, cranial subluxation of C, C ₂ - 22.0%, Hypoplasia C, - 18,6%, Kimmery anomaly - 15,3%, other changes - in 17,0% of children. With ultrasound dopplerography of the main vessels of the head, violations were detected in 76.9% (1.6 findings per surveyed). Asymmetry of blood flow along vertebral arteries was revealed in 50.8%, in internal carotid arteries - in 32.3%, in common carotid arteries - in 16.9%, asymmetry of outflow in the jugular veins - in 33.8%, other disorders in 23.1%. When registering the aggregation function of platelets, violations were detected in 73.9% of children, the mean values for the group below the reference ones.

Thus, the results of the examination can be characterized as polyorganism disorders, more often from the cardiovascular, nervous, musculoskeletal system. In addition to a complex of phenotypic signs of DST, each child had signs of several disorders on the part of organs and systems: changes in the ECG, small heart abnormalities, changes in the cervical spine and asymmetry of blood flow, peculiarities of the structure of internal organs, decreased BMD. On average, the child has more than 8 of these or other features (4 - from the heart, 1,3 - from the abdominal organs, 3,2 - from the cervical vertebrae and vessels). Some of them can be classified as functional (changes in the ECG, the presence of blood flow asymmetry in ultrasound dopplerography, instability of the cervical spine, deformation of the gallbladder), others are morphological in nature (hypoplasia and subluxation of the cervical vertebrae, small cardiac abnormalities, decreased BMD).

Decrease in BMD can make a difference in the formation of early osteochondrosis, scoliosis, and blood supply disorders in the cervical spine. NDST plays a great aetiological role in the genesis of neurocirculatory dysfunction in children. The initial background for its formation is the weakness of the subendothelial layer of the vessels, the developmental anomaly and the weakening of the vertebral ligament apparatus. As a result of this, hemorrhages and injuries of the cervical spine are frequent in childbirth. The processes of bone and bone remodeling for 75-85% are under genetic control. Immediate attempts to reduce the avalanche of bone fractures in old age (two thirds of these at this age are vertebral and femoral) should begin with adolescence and pursue a warning of late osteoporosis.