Connective tissue dysplasia in children and adults

A syndrome such as connective tissue dysplasia is said to occur when a person's body is prone to disorders in the formation of cartilaginous tissue of joints and other tissues from birth. A baby suffering from dysplasia is relatively easy to identify: he is unusually flexible, his joints bend in different directions without problems.

Patients with connective tissue dysplasia already at a young age develop early osteochondrosis, visual impairment, heart valve defects. Accordingly, such people quickly acquire various health problems - in particular, with the musculoskeletal system.

Epidemiology

Connective tissue dysplasia is discussed in cases where there are signs of impaired connective tissue development at the embryonic and postnatal stages, and these disorders cause a failure of homeostasis. The disorder occurs at the level of tissues, organs and the entire organism as a whole: all sorts of morphofunctional pathologies are noted.

The prevalence and incidence of connective tissue diseases reported vary widely, depending on differences in research methodology. [ 1 ] The problem of undifferentiated connective tissue dysplasia (uCTD) is relevant due to the significant frequency of this pathology in the adult population in general, and in particular, among women of reproductive age (7-8%). Patients with dysplasia seek medical help six times more often than patients with other diseases.

The incidence of the disease is not associated with the gender or race of patients.

Causes connective tissue dysplasias

Connective tissue dysplasia is a syndrome that includes a wide range of pathologies. The causes are disorders associated with genetic disorders in the construction of collagen connective tissue fibers. The process mainly affects bone tissue, ligaments and tendons, and skin.

The basic mechanism of connective tissue disorders are gene mutations. Of particular importance are changes in genes responsible for the production of the main protein substance that makes up connective tissue – collagen (sometimes fibrillin). When painful changes occur during the formation of protein fibers, they become less durable and unable to withstand the load. An additional factor in the development of the syndrome may be a lack of magnesium in the body.

Risk factors

Scientists have proven that the following factors contribute to the development of connective tissue dysplasia in a child:

• anemia in the mother during pregnancy;
• threat of termination of pregnancy;
• chronic lack of oxygen in the fetus;
• chronic fetoplacental insufficiency;
• severe or prolonged toxicosis, gestosis;
• chronic pathologies associated with pregnancy (diseases of the endocrine system, kidneys, gastrointestinal tract or respiratory tract).

Pathogenesis

Heterozygous mutations in the type II collagen gene (COL2A1) result in a group of skeletal dysplasias known as type II collagenopathy (COL2pathy).[ 2 ],[ 3 ],[ 4 ] The proα1(I) and proα2(I) chains of collagen 1 are encoded by the COL1A1 and COL1A2 genes, respectively; Quantitative or qualitative defects in type I collagen synthesis typically manifest as type I collagenopathy and osteogenesis imperfecta. Most patients (about 90%) with a clinical diagnosis of osteogenesis imperfecta have a mutation in the COL1A1 or COL1A2 genes, with an autosomal dominant pattern of inheritance. Six other genes, CRTAP, LEPRE1, FKBP10, PP1B, SP7/Osterix (OSX), and SERPINH1, are associated with autosomal recessive forms. [ 5 ], [ 6 ], [ 7 ]

The basic mechanism of development of connective tissue dysplasia, as well as the undifferentiated form of the disease, is caused by a gene mutation, with the involvement of genes responsible for the production and dissimilation of the building protein components of connective tissue, or enzyme substances participating in the above processes. The quantitative formation of the qualitative components of the extracellular matrix changes, fibrillogenesis is upset. Genetic determinants are implemented depending on external factors, or are practically independent of them: this is noted in dysplasia and undifferentiated dysplasia, respectively. Connective tissue dysplasia is characterized by polygenicity and multifactoriality (pathology with a genetic predisposition): we are talking about the mutation of many genes at once, and the random redistribution of paternal and maternal alleles constantly entails the formation of the next unique genotype.

Factors at birth, such as vitamin or macro- and microelement deficiencies, become the underlying causes that create the prerequisites for the development of connective tissue dysplasia. B vitamins stabilize protein metabolism, ascorbic acid with tocopherol potentiate adequate collagen production and act as antioxidants. Micro- and macroelements, such as copper, boron, zinc and silicon, fluorine and calcium, manganese and magnesium, vanadium, phosphorus and selenium, act as cofactors for enzymes that stimulate collagen production and bone mineralization. Their participation in electrolyte metabolism and maintaining acid-base balance is also important. Potassium, magnesium and zinc ions support bone growth and increase the mineral concentration of bone tissue. Any of these factors is of primary importance in the development of the disease. [ 8 ]

Symptoms connective tissue dysplasias

The first signs of connective tissue dysplasia appear in early childhood. This may be either excessive flexibility and hypermobility, or limited joint mobility such as contractures. There may also be physical developmental defects (dwarfism), ligament weakness, fragile bone tissue, various curvatures of the spine, flat feet, deformed rib cage, etc.

Signs of dysplasia are also observed in relation to other organs: the disease can affect the heart, vascular network, and eyes.

The spinal column often suffers: the vertebrae shift so much that the slightest movement compresses the blood vessels, pinches the nerve endings, causes pain, and disturbs consciousness. [ 9 ]

The clinical picture of the disease is striking in its diversity, and this is a huge "minus", since it becomes very difficult to identify the pathology. Therefore, doctors are forced to resort to several methods of laboratory diagnostics at once, as well as instrumental types of research.

Phenotypic signs of connective tissue dysplasia are not always present from birth and can manifest themselves throughout the entire life period. Over time, over the years, most often under the influence of certain unfavorable conditions, the number of dysplastic symptoms and their severity increase and intensify, since the primary homeostasis disorders increase. In this case, unfavorable conditions can be poor nutrition, poor ecology, regular intercurrent pathologies, frequent stress, etc. The primary concern is the constancy of the presence of micro and macroelements that are directly involved in the processes of collagen production, as well as in the regulation of enzymatic activity necessary for rapid and high-quality synthesis.

In general, the above processes are mainly dependent on the balance of calcium and magnesium in the body. For example, magnesium deficiency against the background of normal or excess calcium levels leads to increased activity of proteolytic enzyme substances that cause collagen degradation. As a consequence, there is a severe clinical picture of connective tissue dysplasia.

Magnesium regulates the utilization of calcium in the body. With a magnesium deficiency, calcium is deposited in the bone and soft tissues of various organs. With an excess of magnesium, calcium begins to be poorly absorbed and excreted from the body.

Long-term magnesium deficiency can cause signs of angiospasm, increased blood pressure, myocardial dystrophy, tachycardia, arrhythmia, and increased thrombus formation. Psychoneurological disorders are possible: inattention, depression, phobias or anxiety states, vegetative disorders, headaches and dizziness, insomnia, numbness of the extremities. Visceral signs can be detected in the form of bronchospasms or laryngospasms, spastic constipation or hyperkinetic diarrhea, dyspepsia, gallbladder dyskinesia, abdominal pain.

Chronic magnesium deficiency is additionally manifested by decreased muscle tone and low bone density.

The morphometric characteristics of the skull in connective tissue dysplasia may change due to the peculiarities of hemostasis. Patients are often diagnosed with aortic aneurysms, accompanied by the development of chronic disseminated intravascular coagulation of blood, as a result of stagnation in the aneurysmal cavity and the creation of turbulent flow in the aorta. The formation of ischemic brain lesions, subarachnoid, parenchymatous hemorrhages is possible.

To date, specialists have identified a number of phenotypic signs of CT dysplasia. They can be conditionally divided into visual (those that can be noticed externally) and those that are detected only as a result of a thorough internal examination.

Most patients experience:

• high fatigue, frequent causeless tiredness;
• frequent colds, acute respiratory viral infections;
• tendency to bleeding (large blood loss during tooth extraction, trauma, during menstruation in women);
• dizziness and headaches.

More than 30% of patients experience the so-called “Gothic palate”, malocclusion, hypermobility of joints, premature aging of the face, and flat feet.

Pain in connective tissue dysplasia is disturbing depending on which organ is affected more than others. Thus, periodic and short-term pain in the heart, behind the breastbone and in the hypochondrium, spastic pain along the intestines, headache can often disturb. Unpleasant painful sensations in the joints appear at the stage of osteochondrosis. If there are deformations of the chest or spinal column, then pain in the back and chest occurs with prolonged standing, walking, or even in a sitting position.

Do teeth suffer from connective tissue dysplasia? Many studies have been conducted, as scientists have tried to link changes in the quality of tooth enamel with connective tissue dysplasia, which would allow a more accurate diagnosis of the disease. As a result of such studies, violations of mineralization and formation of tooth enamel in patients with signs of connective tissue dysplasia were found. This is due to insufficient density of enamel prisms per unit volume. In addition, the prisms are chaotically located, and the organic matrix is poorly organized and mineralized. The tendency to abnormal tooth development and the likelihood of associated pathologies is determined individually, since it does not manifest itself in all patients with this disease.

Stages

The course of connective tissue dysplasia is divided into the following stages, or degrees, according to a 4-point scale:

1. score - mild dysplasia
2. points - moderately expressed degree of dysplasia
3. points – severe degree of dysplasia

Pathological signs are assessed on a 2-point scale:

• 0 points – no signs;
• 1 point – signs are present.

Severe connective tissue dysplasia is determined not only by the degree of expression of certain clinical symptoms, but also by the nature of their combinations. For example, only hypermobility, frequent dislocations and subluxations of joints do not always act as signs of significantly expressed dysplasia. But the combination of curvature of the spine with joint crunching, hypermobility, asymmetry, with mental disorders and pronounced cosmetic syndrome allow us to diagnose the extreme stage of the disease.

Forms

There is no consensus among specialists on the classification of connective tissue dysplasia. However, it was decided to divide the syndrome into several groups according to the pathological processes in which the collagen protein is involved. The following systematization is currently recognized as the most reliable:

1. Differentiated connective tissue dysplasia, also known as collagenopathy. [ 10 ] The disease is hereditary, with clear specific symptoms, so it is easy to diagnose.
2. Undifferentiated connective tissue dysplasia includes other variants of similar pathology that are not included in the first group. Undifferentiated varieties of the disease occur much more often, regardless of age, but do not always require treatment.

Differentiated dysplasia of the CT may manifest as Ehlers-Danlos syndrome, [ 11 ] Stickler, [ 12 ] Marfan. [ 13 ]

The undifferentiated form may be accompanied by clinical signs that are not included in the structural series of hereditary pathologies. The most common variants of non-syndromic dysplasia are the marfanoid, ehlersian and MASS phenotypes. [ 14 ]

Marfanoid phenotype	Symptoms of generalized connective tissue dysplasia, asthenic body habitus, arachnodactyly, valvular heart disease, visual impairment, dolichostenomelia.
Ehlersian phenotype	A combination of symptoms of generalized connective tissue dysplasia with a tendency to excessive extensibility of the skin and increased joint mobility.
MASS phenotype	Symptoms of generalized connective tissue dysplasia, cardiac pathologies, defects of the musculoskeletal system, thinning or subatrophy of the skin.

Despite the clarity of the classification, specialists point out the absence of universal signs that form a specific phenotypic affiliation. Each patient has his own, unique defects. Therefore, doctors often use their own version of symptomatic isolation, linking certain pathological changes with connective tissue dysplasia.

• Connective tissue dysplasia of the heart is characterized by the presence of isolated and combined prolapses of the heart valves, myxomatous valvular degeneration.
• Systemic connective tissue dysplasia may be accompanied by multiple organ damage, which is characterized by:

1. bone abnormalities (deformed rib cage, altered length of body segments, arachnodactyly, curvature of the spine, skull deformation, bone fragility, etc.);
2. cardiovascular disorders (aortic dilatation, regurgitation, mitral valve prolapse, early calcification of the mitral annulus, varicose veins, varicocele, frequent hemorrhages);
3. dermatological disorders (extensibility, vulnerability, thinning of the skin, formation of scars, striae, pseudotumors); [ 15 ]
4. muscular and joint disorders (muscular hypotrophy, prolapses, hernias, spondylosis, joint hypermobility, displacements and dislocations, flat feet);
5. ophthalmological disorders (myopia, diseases of the cornea, lens, enophthalmos, etc.);
6. disorders of internal organs (prolapse of kidneys and other organs, diaphragmatic hernia, dolichosigma, polycystic kidney disease, etc.);
7. respiratory disorders (dyskinesia, pulmonary polycystic disease or hypertension, spontaneous pneumothorax).

• Mesenchymal dysplasia of connective tissue is inherited in an autosomal dominant manner and manifests itself in the 20-30 years of age as multiple polyposis of the colon. There is a possibility of malignancy of the process. Numerous osteofibromas or osteomas are found in the cranial bones, soft tissues are affected, dermoid cystic formations, leiomyomas are formed, and teeth fall out prematurely.
• Connective tissue dysplasia of the mitral valve most often manifests itself as its prolapse, less often it is supplemented by prolapses of the aortic or tricuspid valves, an enlarged aortic root and pulmonary trunk. Myocardial contractility indices and volumetric cardiac parameters change. The disorder begins to form at the age of 4-5 years. Auscultation determines the lesion mainly in adolescence. The degree of valve changes depends on the severity of the dysplasia process and the ventricular volume.
• Connective tissue dysplasia of the vessels is accompanied by damage to the elastic arteries with idiopathic expansion of the walls and the formation of a saccular aneurysm. Muscular and mixed arterial vessels are affected: bifurcation aneurysms, pathological tortuosity and loops, dolichoectasias are formed. Veins are affected: tortuosity, varicose areas, hemorrhoids, spider veins are detected, and endothelial dysfunction is observed. The initial stage of vascular damage begins in adolescence, worsening over the years. Blood pressure indicators are disturbed towards idiopathic arterial hypotension.
• Dysplasia of the connective tissue of the spine manifests itself as juvenile osteochondrosis, instability of the vertebrae, intervertebral hernias, vertebrobasilar insufficiency, spondylolisthesis. Disorders occur during the development of thoracodiaphragmatic syndrome and a state of hypermobility, and pathological changes in the spine significantly aggravate the course of the disease.
• Scoliosis with connective tissue dysplasia is dangerous due to its consequences: these can be diseases of internal organs, regular headaches, increased fatigue, fibroids, and kidney prolapse. Most often, intestinal peristalsis is disrupted, and internal organs prolapse.
• Connective tissue dysplasia and aneurysm are constituent features of the vascular syndrome. The formation of saccular aneurysm, bifurcation-hemodynamic aneurysms against the background of arterial dilatations, pathological tortuosity and endothelial dysfunction is observed.
• Dysplasia of intestinal connective tissue is often associated with a high risk of colorectal cancer. Along with intestinal dysfunction, ulcerative colitis, Crom's disease, schistosomiasis, polyposis, and hemorrhoids are often detected. The development of adenomatosis becomes an absolute indication for surgical treatment, and the appearance of adenomas in the duodenum increases the risk of developing duodenal and preampullary cancer.

Livedo in connective tissue dysplasia is another symptom that is found in vascular lesions. It is a vascular neurosis of the spastic atonic type, which is manifested by a violation of blood flow in the capillary network. Livedo is characterized by a bluish color of the skin, which is caused by a peculiar pattern of vessels shining through the skin. The problem most often manifests itself in the area of the shins and thighs, sometimes on the wrists. It can occur as an independent pathology, or become part of a syndrome - in particular, with a neurohormonal disorder or connective tissue dysplasia.

Adult Connective Tissue Dysplasia

Adult patients may notice the onset of painful symptoms already at a young age – approximately 20-24 years. The lesion is accompanied by the following signs:

• Ophthalmological problems in the form of myopia, astigmatism, developmental defects of the fundus, pathology of the cornea and sclera.
• Immunological disorders such as allergic or immunological reactions.
• Joint disorders in the form of dislocations and subluxations.
• Disorders of the nervous system, namely: the emergence of phobic disorders, the development of depressive states or nervous anorexia.

Connective tissue dysplasia in women

Women and men are equally susceptible to developing this disease, but patients are especially concerned about the possibility of becoming pregnant, carrying and giving birth to a healthy child. Scientists have studied this issue and observed all changes in the female body against the background of the undifferentiated form of dysplasia.

According to the resultant assessment, quite a lot of concomitant somatic pathologies were found. Thus, connective tissue dysplasia and pregnancy were accompanied by an increase in the frequency of cardiovascular and neuroendocrine pathologies. Iron deficiency anemia was also noted.

In expectant mothers, chronic extragenital problems were more often exacerbated, mainly pathologies of the respiratory system and ENT organs, as well as diseases of the urinary tract. With timely identification of disorders of the formation of connective tissue structures, it is important to take preventive measures in advance in pregnant women to exacerbate chronic processes, to prevent the development of placental insufficiency.

Connective tissue dysplasia in children

If the diagnosis of connective tissue dysplasia is established in childhood, then the following symptomatic manifestations usually attract attention:

• Disorders of the musculoskeletal system, which are detected in the form of a deformed chest, curvature of the spine such as scoliosis or kyphosis, dysplasia of the hip joints, fragility of bone tissue, excessive joint mobility, segmental disproportion of the skeleton, dislocations and subluxations, and various curvatures of the lower extremities.
• Muscle disorders such as decreased muscle tone in the limbs, frequent sprains, ruptures and tears of the ligamentous apparatus, and tendon damage.
• Nervous system disorders in the form of sleep disturbances, excessive fatigue, periodic dizziness and headaches.
• Defects in the development of the maxillofacial apparatus, which are manifested by impaired growth and abnormal eruption of teeth, a short frenulum of the tongue, enamel hypoplasia, and regular inflammatory processes (for example, gingivitis).
• Cardiovascular problems – most often we are talking about mitral valve prolapse, dilation of the ascending aortic section.

Congenital connective tissue dysplasia

Congenital syndrome can manifest itself in different types of symptom complexes. The most common are:

• Asthenic syndrome, which is characterized by decreased performance, increased fatigue, and various psycho-emotional failures.
• Valvular syndrome is manifested by myxomatous degenerative changes in the valvular system of the heart. Mitral valve prolapse is often diagnosed.
• Vascular syndrome is accompanied by damage to the blood arterial vessels: a saccular aneurysm is formed, and the vascular walls expand.
• Thoracodiaphragmatic syndrome is characterized by deformation of the chest according to the funnel-shaped or keel-shaped type, curvature of the spinal column (increased kyphosis, scoliosis, etc.).
• Bronchopulmonary syndrome may be accompanied by spontaneous pre-eumothorax, tracheobronchomegalosis, and tracheobronchial dyskinesia.

Complications and consequences

Adverse effects of the disease may manifest themselves depending on the degree of damage to the connective tissue. Over the years, the patient develops the following pathologies:

• dysfunction of the autonomic nervous system;
• disorders of the neuropsychiatric sphere;
• cardiovascular pathologies (valvular prolapse, dilation of the aortic root, vascular aneurysms, arrhythmias);
• digestive disorders (gastroesophageal reflux, biliary dyskinesia, irritable bowel syndrome);
• urinary tract problems (prolapsed kidneys, nephropathy, vesicoureteral reflux);
• disorders of the reproductive system (uterine prolapse, varicocele, polycystic ovary syndrome, miscarriages);
• blood disorders (thrombocyto and hemoglobinopathies).

What is the danger of connective tissue dysplasia? The greatest danger is the damage to the cardiovascular and respiratory systems, since it is often accompanied by the development of conditions that pose a threat to the patient's life. For example, changes in the heart and blood vessels often determine the pathogenesis of sudden death: we are talking about valve, vascular, arrhythmic syndromes.

Diagnostics connective tissue dysplasias

Diagnostic measures for detecting connective tissue dysplasia are not always the same and require the use of different medical approaches. Clinical and genetic studies should be a mandatory step, since the pathology is hereditary. As an addition, the doctor practices the following diagnostic principles:

• systematization of patient complaints;
• examination of the body, assessment of proportionality, measurement of the length of limbs and bone sectors;
• assessment of joint mobility;
• conducting a test to determine the patient's ability to grasp his own wrist with the thumb and little finger;
• performing an echocardiogram.

It is also necessary to conduct diagnostics according to the Smolnova criteria (2003) (Major and minor diagnostic criteria), which include: increased skin extensibility, joint hypermobility (ligament sprains, dislocations and subluxations, flat feet), muscle hypotonia, hereditary predisposition to the disease, assessment of signs of joint hypermobility (Beighton criteria). [ 16 ]

Laboratory tests include a urine test: the level of oxyproline and glycosaminoglycans is especially important - these are components that are formed during collagen breakdown. In addition, a blood test, a study of frequent mutations in the PLOD gene, as well as a general biochemical analysis (a detailed assessment of the composition of venous blood) are relevant. In addition, tests are performed on the quality of metabolism in connective tissue, and markers of mineral and hormonal metabolism are determined.

Genetic consultation for connective tissue dysplasia is prescribed to assess the risk of developing severe genetic pathology in a child, to determine ways to prevent the disease. Consultation is necessary if one of the spouses is sick with dysplasia, if there are suspicious test results or external painful manifestations. The following usually act as consultants:

• geneticist;
• clinical geneticist;
• genetic counselor;
• another specialist in a narrow medical field.

If necessary, genetic analysis may be recommended, which helps to assess the state of certain genes in the DNA molecule and provides information on how predisposed a person is to a particular disease - in particular, to the development of connective tissue dysplasia. Genetic analysis is recognized as a scientific basis for calculating genetic load.

Instrumental diagnostics include ultrasound echography, magnetic resonance imaging, computed tomography, electromyography (assessment of electrical activity of muscles), and X-ray examination.

Differential diagnosis

Differential diagnostics are carried out with the following pathologies:

• Louis-Dietz syndrome (accompanied by cleft uvula/palate, clubfoot, instability of the cervical vertebrae, hypertelorism);
• Martin-Bell syndrome; [ 17 ]
• Shprintzen-Goldberg syndrome (accompanied by mental retardation);
• Weil-Marchesani syndrome (characterized by brachydactyly, hypermobility of joints);
• congenital contractural arachnodactyly (occurs with contractural joint changes);
• ectopia lentis syndrome (not accompanied by signs of aortic dilation);
• homocystinuria (characterized by thrombosis, mental retardation);
• Ehlers-Danlos syndrome (characterized by valve insufficiency, characteristic facial features, arterial aneurysm). [ 18 ]

Treatment connective tissue dysplasias

There are no doctors who specialize only in connective tissue dysplasia. Children are examined and treated by a pediatrician, with the support of other specialists: geneticist, endocrinologist, orthopedist, cardiologist, etc.

For more information about treatment methods, read this article.

Prevention

If we talk about the primary prevention of connective tissue dysplasia, then it is mandatory for the mother to lead a healthy lifestyle, establish a rational work and rest regime, promptly treat diseases, eat a balanced diet, and engage in thoughtful physical activity.

Secondary prevention involves constant dynamic monitoring of patients with dysplasia, compliance with preventive and therapeutic measures.

Obstetricians and gynecologists should remember the importance of periconceptional and perinatal prevention. The first involves conducting a full clinical examination of the woman, assessing the presence of teratogenic and other negative factors, prescribing drugs with magnesium and folic acid. At the same time, placental insufficiency is prevented, future parents are consulted on the importance of breastfeeding, the physical development of the baby, and taught the basics of child hygiene.

Forecast

Often, patients suffering from the disease already at a young age acquire other health problems - in particular, early osteochondrosis, visual impairment, mitral valve prolapse. The syndrome should not be ignored under any circumstances, despite its genetic origin: under the influence of certain factors, the disease can both slow down its development and worsen it.

In the last century, the scale of development of connective tissue dysplasia was much smaller: people had practically no magnesium deficiency - the diet included cereals, vegetables, greens, and all products were environmentally friendly. Today, we are dealing with a completely changed diet. Children often prefer fast food and products with artificial filling. But proper nutrition alone can significantly slow down the pathological processes typical for dysplasia.

How long do people with connective tissue dysplasia live? There is no single answer to this question, since life expectancy depends entirely on what specific disorders and changes have occurred in the patient's body and how pronounced they are. For example, if dysplasia affects cardiac tissue, the patient may die within a couple of months.

Much depends on the chosen treatment tactics, and failure to consult a doctor, or an incorrect diagnosis (and, as a consequence, incorrect treatment of the syndrome) can be especially dangerous.

Disability

The issue of assigning a disability group for connective tissue dysplasia is decided individually and separately in each specific case. There is a greater chance of receiving disability for a neurological or orthopedic profile, but everything depends on the degree and severity of the disease, the effectiveness of treatment and the duration of stay on dispensary records.

Do they take you into the army?

The diagnosis of connective tissue dysplasia in itself is not a reason for exemption from conscription, but this issue can be resolved individually by the military commissariat staff. In uncomplicated cases, in which the function of the joints is not impaired, the young man can be taken into service and assigned category B. In other situations, all violations caused by dysplasia processes are taken into account - for example, abnormal position of the joints, shortening or limitation of mobility of the arms and legs, incorrect amplitude of movement.

The conscript must fully provide the members of the military medical commission with evidence of his own unfitness for service. Under appropriate circumstances, the military registration and enlistment office doctor will give the young man a referral for additional examination.

Celebrities with connective tissue dysplasia

When you leaf through magazines with photos of famous people, you never think that they also have health problems - and these problems can be serious. In fact, actors and musicians are the same people as you and me, and some of them have to create and work, despite all sorts of obstacles and even pain.

• Sarah Hyland is an actress who played in the TV series Modern Family. At the age of nine, she was diagnosed with kidney dysplasia, and the subsequent long-term treatment was practically ineffective. Only in 2012, she had to undergo a kidney transplant, which significantly improved the actress's condition, but still did not lead to a complete cure.
• Michael Berryman is an actor known for his unusual appearance caused by a genetic disorder called hypohidrotic dysplasia. The man has a high forehead, sunken cheeks, and wrinkled skin. Thanks to these external characteristics, the actor successfully plays the roles of all sorts of monsters, mutants, and villains.
• Melanie Gaydos is a famous model from the United States who has an unusual appearance caused by ectodermal dysplasia. Melanie looks both frightening and fascinating, and problems with hair, nails, teeth and joints have not become an obstacle in her dizzying modeling career.

Doctors note that connective tissue dysplasia is not always characterized by bright and painful symptoms, loss of ability to work and fading of vital activity. The disease can and should be fought, while leading a fairly active lifestyle.