Connective tissue dysplasia in children and adults

Such a syndrome as connective tissue dysplasia is said to be when the human body is prone to disturbances in the formation of cartilage tissue of joints, as well as other tissues, from birth. A kid suffering from dysplasia is relatively easy to identify: he is unusually flexible, his joints flex without problems in different directions.

In patients with connective tissue dysplasia, early osteochondrosis develops at a young age, impaired vision, heart valve defects. Accordingly, such people quickly find various health problems - in particular, with the musculoskeletal system.

Epidemiology

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

The prevalence and frequency of reported connective tissue diseases are very different, depending on differences in research methodology. [1] The problem of undifferentiated connective tissue dysplasia (nDST) is relevant due to the significant frequency of this pathology in the adult population as a whole, and in particular among women of reproductive age (7-8%).  For the help of doctors, patients with dysplasia turn six times more often than patients with other diseases.

The incidence is not related to the gender and race of the patients.

Causes of the connective tissue dysplasia

Connective tissue dysplasia is a syndrome that includes an extensive range of pathologies. The causes are disorders associated with genetic disorders in the construction of collagen connective tissue fibers. The process mainly captures bone tissue, ligament and tendon apparatus and skin integument.

The underlying mechanism of connective tissue disorders is gene mutation. A special role is played by changes in the genes responsible for the production of the main protein substance that makes up the connective tissue - we are talking about collagen (sometimes fibrillin). When painful changes occur during the formation of protein fibers, they become less durable, 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 proved that the following factors contribute to the development of connective tissue dysplasia in a child:

• maternal anemia during pregnancy;
• threatened abortion;
• chronic fetal oxygen deficiency;
• chronic fetoplacental insufficiency;
• severe or prolonged toxicosis, gestosis;
• chronic pathologies associated with pregnancy (diseases of the endocrine system, kidneys, organs of the gastrointestinal tract or respiratory tract).

Pathogenesis

Heterozygous mutations in the type II collagen gene (COL2A1) lead to a group of skeletal dysplasias known as type II collagenopathy (COL2pathy). [2],  [3],  [4] Proα1 chains (I) and proα2 (I) collagen 1 encoded genes COL1A1 and COL1A2, respectively; Quantitative or qualitative defects in the synthesis of type I collagen are usually manifested in the form of type I collagenopathy and imperfect osteogenesis. Most patients (about 90%) with a clinical diagnosis of osteogenesis imperfecta have a mutation in the COL1A1 or COL1A2 genes with an autosomal dominant type 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 for the development of connective tissue dysplasia, as well as the undifferentiated form of the disease, is caused by gene mutation with the involvement of genes responsible for the production and dissimilation of building protein components of connective tissue, or enzyme substances involved in these processes. The quantitative formation of the qualitative components of the extracellular matrix is changing, fibrillogenesis is upset. Genetic determinants are carried out depending on external factors, or practically do not depend on them: this is noted with dysplasia and undifferentiated dysplasia, respectively. Polygenicity and multifactoriality (pathology with a genetic predisposition) are inherent in connective tissue dysplasia: we are talking about mutations of many genes at once, and the random redistribution of paternal and maternal alleles constantly entails the formation of the next one-of-a-kind genotype.

Factors at birth - for example, vitamin or macro and micronutrient deficiencies - become the underlying causes that create the prerequisites for the development of connective tissue dysplasia. B-group vitamins stabilize protein metabolism, ascorbic acid with tocopherol potentiate adequate collagen production, and also act as antioxidants. Micro and macro elements - copper, boron, zinc and silicon, fluorine and calcium, manganese and magnesium, vanadium, phosphorus and selenium - act as cofactors of enzyme substances that stimulate collagen production and saturation of bones with minerals. It is also important that they participate in electrolyte metabolism and maintain acid-base balance. Potassium, magnesium and zinc ions support bone growth and enhance the mineral concentration of bone tissue. In the development of the disease, any of these factors is of paramount importance. [8]

Symptoms of the connective tissue dysplasia

The first signs of connective tissue dysplasia appear even in early childhood. This can be both excessive flexibility and hypermobility, as well as limited mobility of the joints according to the type of contractures. Physical developmental defects (dwarfism), ligamentous weakness, brittle bone tissue, various curvatures of the spine, flat feet, deformed chest, etc. Also happen.

Signs of dysplasia are noted in relation to other organs: the disease can affect the heart, vasculature, eyes.

The vertebral column often suffers: the vertebrae are displaced so much that with the slightest movement there is a compression of the vessels, nerve endings are impaired, pain occurs, and consciousness is impaired. [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, as well as instrumental types of research.

Phenotypic signs in connective tissue dysplasia are not always present from birth and can occur throughout the entire life period. Over time, over the years, most often - under the influence of certain adverse conditions, the number of dysplastic symptoms and their severity increases and intensifies, as primary disorders of homeostasis increase. In this case, poor nutrition, poor ecology, regular intercurrent pathologies, frequent stresses, etc. Can become unfavorable conditions. The constancy of the presence of micro and macro elements that are directly involved in the processes of collagen production, as well as in the regulation of enzymatic activity necessary for fast and high-quality synthesis.

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

Magnesium regulates the utilization of calcium in the body. With a deficiency of magnesium, 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.

A long-term lack of magnesium can cause signs of angiospasm, increased blood pressure, myocardial dystrophy, tachycardia, arrhythmia, and increased thrombosis. Neuropsychiatric disorders are possible: inattention, depression, phobias or anxiety, autonomic disorders, headaches and dizziness, insomnia, numbness of limbs. Visceral signs can be detected in the form of broncho or laryngospasm, spastic constipation or hyperkinetic diarrhea, dyspepsia, gallbladder dyskinesia, and abdominal pain.

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

The morphometric characteristics of the skull with connective tissue dysplasia may vary due to the characteristics of hemostasis. Patients are often diagnosed with aortic aneurysms, accompanied by the development of chronic disseminated intravascular coagulation, as a result of stagnation in the aneurysm cavity and the creation of a turbulent current in the aorta. Perhaps the formation of ischemic brain lesions, subarachnoid, parenchymal hemorrhages.

To date, experts have identified a number of phenotypic signs of CT dysplasia. They can be conditionally divided into visual (those that can be seen externally) and those that are detected only by the results of a thorough internal examination.

Most patients have:

• high fatigue, frequent causeless fatigue;
• frequent colds, SARS;
• tendency to bleeding (large blood loss during tooth extraction, with injuries, during menstruation in women);
• dizziness and pain in the head.

More than 30% of patients have the so-called "Gothic sky", malocclusion, joint hypermobility, premature aging of the face, flat feet.

Pain in connective tissue dysplasia is disturbing, depending on which organ is affected more than others. So, periodic and long-term pains in the heart, behind the sternum and in the hypochondrium, spastic pain along the intestine, and headache can often disturb. Unpleasant pain in the joints appears at the stage of joining osteochondrosis. If there are deformations of the chest or spinal column, then back and chest pains occur with prolonged standing, walking, or even in a sitting position.

Do teeth suffer from connective tissue dysplasia? A lot of research was carried out, as scientists tried to connect the change 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 work, violations of mineralization and formation of tooth enamel were found in patients with signs of connective tissue dysplasia. This is due to the insufficient packing density of enamel prisms per unit volume. In addition, the prisms are randomly arranged, and the organic matrix is poorly organized and mineralized. The tendency to improper development of teeth and the likelihood of pathologies associated with this are determined individually, since not all patients with this disease manifest themselves.

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. score - moderate severe degree of dysplasia
3. score - severe degree of dysplasia

Pathological signs are evaluated on a 2-point scale:

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

Severe connective tissue dysplasia is determined not only by the severity of certain clinical symptoms, but also by the nature of their combinations. For example, only hypermobility, frequent dislocation and subluxation of the joints do not always act as signs of significantly pronounced dysplasia. But the combination of curvature of the spine with articular crunch, hypermobility, asymmetry, with mental disorders and severe cosmetic syndrome make it possible to diagnose the extreme degree of the disease.

Forms

There is no consensus among experts regarding the classification of connective tissue dysplasia. However, the syndrome was decided to subdivide into several groups according to the pathological processes in which the collagen protein is involved. The most reliable at the moment is recognized as such a systematization:

1. Differentiated connective tissue dysplasia, which is also called the term collagenopathy. [10]The disease is of a hereditary type, with clear specific symptoms, therefore it is easily amenable to diagnosis.
2. Undifferentiated connective tissue dysplasia includes other variants of a 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 CT dysplasia can manifest itself in the form of 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 extraindromic dysplasia, such as marfanoid, elersovidny and MASS-phenotype. [14]

Morphanoid phenotype	Symptoms of generalized connective tissue dysplasia, asthenic addition of the body, arachnodactyly, valvular heart disease, visual disturbances, dolichostenomeliya.
Ellersoid phenotype	The combination of symptoms of generalized connective tissue dysplasia with a tendency to excessive extensibility of the skin and increased articular 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, experts point out the absence of universal characters forming a specific phenotypic affiliation. Each patient has its own unique defects. Therefore, doctors often use their own version of symptomatic isolation, linking certain pathological changes with connective tissue dysplasia.

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

1. bone disorders (deformed chest, altered length of body segments, arachnodactyly, spinal curvature, cranial deformity, bone fragility, etc.);
2. cardiovascular disorders (aortic enlargement, regurgitation, mitral valve prolapse, earlier calcification of the mitral ring, varicose veins, varicocele, frequent hemorrhages);
3. dermatological disorders (extensibility, vulnerability, thinning of the skin, the formation of scars, striae, pseudotumors); [15]
4. muscle and joint disorders (muscular hypotrophy, prolapse, hernia, spondylosis, articular hypermobility, displacements and dislocations, flat feet);
5. ophthalmic disorders (myopia, diseases of the cornea, lens, enophthalmos, etc.);
6. disorders of the internal organs (prolapse of the kidneys and other organs, hernia of the diaphragm, dolichosigma, renal polycystic, etc.);
7. respiratory disorders (dyskinesias, pulmonary polycystic or hypertension, spontaneous pneumothorax).

• Mesenchymal dysplasia of the connective tissue is inherited autosomally dominantly, manifests itself in multiple colon polyposis at the age of 20-30. 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 form, and teeth fall out prematurely.
• Dysplasia of the connective tissue of the mitral valve is most often manifested by its prolapse, less often supplemented by prolapse of the aortic or tricuspid valves, an enlarged aortic root and pulmonary trunk. Myocardial contractility and volumetric cardiac parameters are changing. Violation begins its formation from 4-5 years of age. Auscultation of the lesion is determined mainly in adolescence. The degree of valve changes depends on the severity of the dysplasia process and on ventricular volume.
• Dysplasia of the connective tissue of blood vessels is accompanied by damage to the elastic arteries with idiopathic expansion of the walls and the formation of saccular aneurysm. Muscular and mixed arterial vessels are affected: bifurcation aneurysms, pathological tortuosities and loops, dolichoectasia are formed. Veins are affected: tortuosity, varicose areas, hemorrhoids, spider veins are detected, endothelial dysfunction is observed. The initial stage of vascular damage starts already from adolescence, worsening over the years. Blood pressure indicators are disturbed towards idiopathic arterial hypotension.
• Dysplasia of the connective tissue of the spine is manifested by juvenile osteochondrosis, vertebral instability, intervertebral hernias, vertebrobasilar insufficiency, spondylolisthesis. Violations occur during the development of thoracodiaphragmatic syndrome and the state of hypermobility, and pathological changes in the spine significantly aggravate the course of the disease.
• Scoliosis with connective tissue dysplasia is dangerous for its consequences: it can be diseases of internal organs, regular pain in the head, increased fatigue, fibroids, and drooping kidneys. Most often, intestinal motility is disturbed, internal organs are lowered.
• Connective tissue dysplasia and aneurysm are constituent signs of vascular syndrome. The formation of saccular aneurysm, bifurcation-hemodynamic aneurysms against the background of arterial enlargement, pathological tortuosities and endothelial dysfunction is observed.
• Intestinal dysplasia is often associated with a high risk of colorectal cancer. Along with impaired intestinal function, ulcerative colitis, Crom's disease, schistomatosis, polyposis, hemorrhoids are often found. The development of adenomatosis becomes an absolute indication for surgical treatment, and the appearance of adenomas in the duodenum 12 increases the risk of the formation of a duodenal and preampular cancer.

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

Connective tissue dysplasia in adults

Adult patients can detect the appearance of painful symptoms at a young age - approximately 20-24 years. The defeat is accompanied by such signs:

• Ophthalmic problems in the form of myopia, astigmatism, defects in the development of the fundus, pathology of the cornea and sclera.
• Immunological disorders according to the type of allergic or immunological reactions.
• Joint disorders in the form of dislocations and subluxations.
• Violations of the nervous system, namely: the appearance of phobic disorders, the development of depressive states or anorexia nervosa.

Connective tissue dysplasia in women

Women and men are equally susceptible to the development of this disease, however, patients express particular concern about the possibility of becoming pregnant, carrying and having a healthy baby. Scientists studied this issue and observed all changes in the female body against the background of an undifferentiated form of dysplasia.

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

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

Connective tissue dysplasia in children

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

• Disorders of the musculoskeletal system, which are found in the form of a deformed chest, curvature of the spinal column according to the type of scoliosis or kyphosis, dysplasia of the hip joints, fragility of bone tissue, excessive articular mobility, segmental disproportionality of the skeleton, dislocations and subluxations, diverse varieties.
• Muscle disorders, such as decreased muscle tone of the limbs, frequent sprains, tears and tears of the ligamentous apparatus, and tendon damage.
• Disorders of the nervous system 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 improper teething, a short frenum of the tongue, enamel hypoplasia, regular inflammatory processes (for example, gingivitis).
• Cardiovascular problems - most often it is a prolapse of the mitral heart valve, expansion of the ascending aortic section.

Congenital connective tissue dysplasia

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

• Asthenic syndrome, which is characterized by reduced working capacity, increased fatigue, various psychoemotional 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 blood vessels: baggy aneurysm is formed, the vascular walls expand.
• Thoraco-diaphragmatic syndrome is characterized by chest deformity in the funnel or keeled type, curvature of the spinal column (increased kyphosis, scoliosis, etc.).
• Bronchopulmonary syndrome may be accompanied by spontaneous premothorax, tracheobronchomegulation, tracheobronchial dyskinesia.

Complications and consequences

Adverse effects of the disease may occur 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 neuropsychic sphere;
• cardiovascular pathologies (valvular prolapse, expansion of the aortic root, vascular aneurysms, arrhythmias);
• digestive disorders (gastroesophageal reflux, biliary dyskinesia, irritable bowel syndrome);
• problems in the urinary tract (prolapse of the kidneys, nephropathy, vesicoureteral reflux);
• genital disorders (prolapse of the uterus, varicocele, ovarian polycystosis, miscarriage);
• blood disorders (thrombocyte and hemoglobinopathies).

What is the danger of connective tissue dysplasia? The greatest danger is damage to the cardiovascular and respiratory system, 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 a sudden death: we are talking about valve, vascular, arrhythmic syndromes.

Diagnostics of the connective tissue dysplasia

Diagnostic measures to detect connective tissue dysplasia are not always the same and require the use of different medical approaches. Clinical genetic studies should be an obligatory moment, since the pathology is hereditarily determined. As a supplement, the doctor practices the following diagnostic principles:

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

Diagnostics should also be carried out according to the criteria of Smolnova (2003) (Large and small diagnostic criteria), which include: increased skin extensibility, hypermobility of the joints (sprain, dislocation and subluxation, flat feet), muscle hypotension, hereditary predisposition to the disease, assessment of signs of joint hypermobility (Beiton criteria). [16]

Laboratory tests include a study of urinary fluid: the level of oxyproline and glycosaminoglycans is especially important - these are the components that form during the 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, analyzes 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, and 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. As consultants usually act:

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

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

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

Differential diagnosis

Differential diagnosis is carried out with the following pathologies:

• Louis-Dietz syndrome (accompanied by splitting of the tongue / palate, clubfoot, instability of the cervical vertebrae, hypertelorism);
• Martin-Bell Syndrome; [17]
• Sprintzen-Goldberg syndrome (accompanied by mental retardation);
• Weil-Marchezani syndrome (characterized by brachidactyly, with joint mobility);
• congenital contractural arachnodactyly (occurs with contractural articular changes);
• ectopic lens syndrome (not accompanied by signs of aortic dilatation);
• homocystinuria (characterized by thrombosis, mental retardation);
• Ehlers-Danlos syndrome  (characterized by valvular insufficiency, characteristic facial features, arterial aneurysm). [18]

Treatment of the connective tissue dysplasia

Doctors specializing only in connective tissue dysplasia do not exist. The pediatrician examines and treats the children, with the support of other specialists: genetics, endocrinologist, orthopedist, cardiologist, etc.

Read more about treatment methods in this article .

Prevention

If we talk about the primary prevention of connective tissue dysplasia, it is mandatory for the mother to maintain a healthy lifestyle, establish a rational regime of work and rest, timely treatment of diseases, a balanced diet, and thought-out physical activity.

Secondary prophylaxis provides for constant dynamic monitoring of patients with dysplasia, compliance with preventive and therapeutic measures.

Obstetrician-gynecologists should remember the importance of periconceptional, perinatal prophylaxis. The first is to conduct a full-scale clinical examination of a woman, assess the presence of teratogenic and other negative factors, and prescribe drugs with magnesium and folic acid. At the same time, the prevention of placental insufficiency, the consultation of future parents on the importance of breastfeeding, the physical development of the baby, and teaching the basics of child hygiene are carried out.

Forecast

Often, patients suffering from the disease already at a young age gain other health problems - in particular, early osteochondrosis, visual impairment, mitral valve prolapse. The syndrome cannot be ignored in any case, despite its genetic origin: under the influence of certain factors, the disease can either slow down its development or aggravate it.

As far back as the last century, the scale of development of connective tissue dysplasia was much smaller: there was practically no lack of magnesium in people - cereals, vegetables, greens were present in the diet, and all products were environmentally friendly. Today we are dealing with a completely changed diet. Children often give preference to fast food and products with artificial filling. But proper nutrition alone can significantly slow down the pathological processes typical of dysplasia.

How many live with connective tissue dysplasia? There can be no single answer to this question, since life expectancy depends entirely on what specific disorders and changes occurred in the patient’s body, and how pronounced they are. For example, if dysplasia affects the heart tissue, then the patient may die within a couple of months.

Much depends on the chosen treatment tactics, and it becomes especially dangerous not to see a doctor, or an incorrect diagnosis (and as a result, an incorrect treatment of the syndrome).

Disability

The issue of assigning a disability group for connective tissue dysplasia is decided individually and separately in each case. There are more chances to get a disability according to the neurological or orthopedic profile, but it all depends on the degree and severity of the disease, on the effectiveness of treatment and the length of stay at the dispensary.

Are they taking into the army?

The diagnosis of connective tissue dysplasia in itself is not a reason for exemption from conscription, but this issue can be decided individually by members of the military commissariat. In uncomplicated cases in which the function of the joints is not impaired, a young man can be hired with assignment of category B. In other situations, all violations caused by dysplasia processes are taken into account - for example, impaired position of joints, shortening or limiting the mobility of arms and legs, incorrect range of motion.

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

Celebrities with connective tissue dysplasia

When leafing through magazines with photographs of famous people, you never think about the fact that they also have health problems - and these problems can be serious. Actually, the actors and musicians are the same people as you and I, 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 The American Family. Even at the age of nine, she was found to have dysplasia of the kidneys, and the subsequent long treatment was practically inconclusive. Only in 2012 she had to undergo a kidney transplant operation, which significantly improved the condition of the actress, but still did not lead to a complete cure.
• Michael Berriman is an actor known for his unusual appearance caused by a genetic disease - hypohydrotic dysplasia. The man has a high forehead, sunken cheeks, wrinkled skin. Thanks to such external characteristics, the actor successfully plays the role of all kinds of monsters, mutants, villains.
• Melanie Gaidos is a well-known model from the United States that has a non-standard appearance caused by ectoderm dysplasia. Melanie looks both frightening and bewitching, and problems with hair, nails, teeth and joints did not interfere in her dizzying modeling career.

Doctors note that far from always connective tissue dysplasia is bright and painful symptoms, disability and the extinction of vital activity. The disease can and must be fought, while leading a fairly active lifestyle.