Mosaic form of Down syndrome: how to define

Genetic pathology caused by changes in the 21st chromosome is a mosaic Down syndrome. Consider its features, methods of diagnosis, treatment and prevention.

Down's disease belongs to the most common congenital genetic disorders. It is characterized by a marked lag in mental development and a number of intrauterine anomalies. Because of the high fertility of children with trisomy, a lot of research has been done. Pathology is found in representatives of all the peoples of the world, so there is no geographical or racial dependence.

[1], [2]

Epidemiology

According to medical statistics, Down syndrome occurs in 1 child for 700-1000 births. Epidemiology of the disorder is associated with certain factors: hereditary predisposition, bad habits of parents and their age.

The pattern of the spread of the disease is not related to the geographical, sexual, national or economic status of the family. Trisomy is caused by disabilities in the development of the child.

[3], [4], [5], [6]

Causes of the mosaic Down syndrome

The main causes of mosaic syndrome of Down are associated with genetic disorders. A healthy person contains 23 pairs of chromosomes: female karyotype 46, XX, male 46, XY. One of the chromosomes of each pair is transmitted from the mother, and the second from the father. The disease develops as a result of a quantitative violation of autosomes, that is, extra genetic material joins the 21st pair. Trisomy on the 21st chromosome is responsible for the symptoms of the defect.

Mosaic syndrome can occur for the following reasons:

• Somatic mutations in the zygote or in the early stages of crushing.
• Redistribution in somatic cells.
• Segregation of chromosomes with mitosis.
• Inheritance of a genetic mutation from a mother or father.

The formation of abnormal gametes can be associated with certain diseases of the genital area of parents, radiation, smoking and alcoholism, the use of medications or narcotic substances, as well as the environmental situation of the place of residence.

About 94% of the syndrome is associated with simple trisomy, that is: karyotype 47, XX, 21+ or 47, XY, 21+. Copies of the 21st chromosome are present in all cells, since during division of the meiosis in the parental cells, division of the pair chromosomes is disrupted. About 1-2% of cases are caused by a violation of mitosis of the embryo cells at the stage of gastrula or blastula. Mosaicism is characterized by trisomy in the derivatives of the affected cell, while the rest have a normal chromosomal set.

With the translocation form, which occurs in 4-5% of patients, the 21st chromosome or a fragment of it is translocated to the autosome under meiosis, penetrating with it into the newly formed cell. The main objects of translocation are 14, 15, less often 4, 5, 13 or 22 chromosomes. Such changes can be random or inherited from a parent who acts as a carrier of translocation and a normal phenotype. If there are such violations in the father, the risk of having a sick child is 3%. With the carrier on the part of the mother - 10-15%.

[7], [8], [9], [10]

Risk factors

Trisomy is a genetic disease that can not be acquired during life. Risk factors for its development are not related to lifestyle or ethnicity. But the chances of having a sick child increase in such circumstances:

• Late childbirth - women of 20-25 years of age have minimal chances of having a baby with a disease, but after 35 years the risk increases significantly.
• Age of the father - many scientists claim that the genetic disease depends not so much on the age of the mother, as on how old the father is. That is, the older the man, the higher the chances of pathology.
• Heredity - medicine is known to the case when the defect was inherited from close relatives, taking into account the fact that both parents are absolutely healthy. In this case, there is a predisposition to only certain types of syndrome.
• Incest - marriage between blood relatives entails genetic mutations of varying severity, including trisomy.
• Bad habits - negatively reflect on the health of the baby's future, so tobacco abuse during bearing can lead to a genomic anomaly. Similar is observed with alcoholism.

There are suggestions that the development of malaise may be due to the age at which the grandmother gave birth to the mother and other factors. Thanks to preimplantation diagnostics and other research methods, the risk of giving birth to a Down's child is significantly reduced.

[11], [12], [13]

Pathogenesis

The development of genetic disease is associated with a chromosomal abnormality, in which the patient instead of 46 appears 47 chromosomes. The pathogenesis of the mosaic syndrome has a different developmental mechanism. Parental gametes of parents have a normal number of chromosomes. Their fusion led to the formation of a zygote with a karyotype of 46, XX or 46, XY. In the process of dividing the original DNA cell, a failure occurred, and the distribution was incorrect. That is, part of the cells received a normal karyotype, and a part - a pathological one.

This kind of anomaly occurs in 3-5% of cases of the disease. It has a positive prognosis, because healthy cells partially compensate for the genetic disorder. Such children are born with external signs of the syndrome and developmental lag, but their survival rate is much higher. They have fewer internal pathologies incompatible with life.

[14], [15], [16], [17]

Symptoms of the mosaic Down syndrome

An abnormal genetic feature of the organism, arising with an increase in the number of chromosomes, has a number of external and internal signs. Symptoms of mosaic Down's syndrome are manifested by a lag in mental and physical development.

The main physical symptoms of the disease:

• Small and slow growth.
• Muscle weakness, decreased strength function, weakness of the abdominal cavity (sagging belly).
• Short, thick neck with wrinkles.
• Short limbs and a large distance between the thumb and forefinger on the legs.
• Specific skin fold on the palms of the children.
• Low set and small ears.
• Distorted form of tongue and mouth.
• Twisted teeth.

The disease causes a number of deviations in development and health. First of all, it is cognitive backwardness, heart defects, problems with teeth, eyes, back, hearing. Propensity to frequent infectious and respiratory diseases. The degree of manifestation of the disease depends on the inherent factors and the right treatment. Most of the kids are trained, despite the mental, physical and mental lag.

First signs

Mosaic Down's syndrome has less pronounced symptoms, in contrast to the classical form of the disorder. The first signs can be seen on ultrasound at 8-12 weeks of pregnancy. They are manifested by an increase in the collar zone. But ultrasound does not give a 100% guarantee of the presence of the disease, but allows you to assess the likelihood of malformations in the fetus.

The most common external symptoms, with their help, doctors presumably diagnose the pathology immediately after the birth of the baby. The defect is characterized by:

• Cracked eyes.
• A "flat" face.
• Short-headedness.
• Thickened cervical skin fold.
• Semilunar fold at the inner corner of the eyes.

With further examination, the following problems are identified:

• Decreased muscle tone.
• Increased joint mobility.
• Deformation of a pile of cells (keeled, funnel-shaped).
• Broad and short bones, flat occiput.
• Deformed ears and folded nose.
• A small arched sky.
• Pigmentation along the edge of the iris.
• Transverse palmar fold.

In addition to external symptoms, the syndrome has internal disorders:

• Congenital heart diseases and other disorders of the cardiovascular system, anomalies of large vessels.
• Pathologies on the part of the respiratory system caused by the peculiarities of the structure of the oropharynx and a large tongue.
• Strabismus, congenital cataract, glaucoma, hearing impairment, hypothyroidism.
• GI disorders: intestinal stenosis, atresia of the anus and rectum.
• Hydronephrosis, kidney hypoplasia, hydroureter.

The above symptomatology requires constant treatment to maintain the normal state of the body. It is congenital malformations that cause a short life of downs.

[18]

External signs of a mosaic form of Down's Syndrome

In most cases, external signs of a mosaic form of Down's syndrome appear immediately after birth. Because of the high prevalence of gene pathology, its symptoms are studied in detail and described.

Changes in the 21st chromosome are characterized by such external signs:

1. Abnormal structure of the skull.

This is the most noticeable and pronounced symptom. Normally, babies have a larger head than adults. Therefore, any deformations are visible immediately after birth. The changes concern the structure of the cranium and the facial skull. The patient has a disproportion in the region of the bones of the crown. Also there is a flattening of the occiput, a flat face and pronounced ophthalmic hypertelorism.

2. Disturbances of development of eyes.

A person with this disease resembles a representative of the Mongoloid race. Similar changes appear immediately after birth and persist throughout life. In addition, it is worth to cancel strabismus in 30% of patients, the presence of a skin fold at the inner corner of the eyelid and pigmentation of the iris of the eye.

3. Congenital defects of the oral cavity.

This type of disorder is diagnosed in 60% of patients. They create difficulties in feeding a child, slowing his growth. A person with a syndrome changes the surface of the tongue due to a thickened papillary layer (sulcus tongue). In 50% of cases there is a Gothic sky and violations of the sucking reflex, half-open mouth (muscle hypotension). In rare cases, there are anomalies such as "wolf mouth" or "hare lip".

4. Incorrect shape of the ears.

This violation occurs in 40% of cases. Underdeveloped cartilages form an abnormal auricle. The ears can be protruded in different directions or located below eye level. Despite the fact that the defects are cosmetic, they can cause serious problems with hearing.

5. Additional skin folds.

There are 60-70% of patients. Each skin fold is caused by underdevelopment of bones and their irregular shape (skin is not stretched). This external sign of trisomy is manifested as an excess of skin on the neck, thickenings in the elbow joint and a transverse fold on the palm.

6. Pathology of development of the musculoskeletal system

They arise because of a violation of the fetal development of the fetus. The connective tissue of the joints and some bones do not have time to fully form before birth. The most common abnormalities: a short neck, increased mobility of joints, short limbs and deformed fingers.

7. Deformation of the chest.

This problem is associated with underdevelopment of bone tissue. In patients, deformity of the thoracic spine and ribs is observed. Most often diagnose the bulging sternum above the surface of the chest, that is, the keel shape and deformation, in which there is a funnel-shaped depression in the solar plexus area. Both disorders persist as they grow and grow. They provoke disturbances in the structure of the respiratory system and the cardiovascular system. These external symptoms indicate a poor prognosis of the disease.

The main feature of the mosaic form of Down's syndrome is that with it many of the above symptoms can be absent. This complicates the differentiation of pathology with other chromosomal abnormalities.

[19], [20], [21]

Forms

The syndrome has several types, consider them:

• Mosaic - extra chromosome is not contained in all cells of the body. This disease is 5% of all its cases.
• Family - occurs in 3% of patients. Its peculiarity is that each of the parents has a number of abnormalities that are not expressed externally. During fetal development, part of the 21st chromosome is attached to the other, making it a pathological carrier of information. Parents with this defect have children with a syndrome, that is, the anomaly is inherited.
• Duplicating part of the 21st chromosome is a rare kind of disease, the feature of which is that the chromosomes are not able to divide. That is, there are additional copies of the 21st chromosome, but not all genes. Pathological symptoms and external manifestations develop if duplicate fragments of the gon, which cause a clinical picture of the defect, are duplicated.

[22],

Complications and consequences

Chromosome mosaicism causes consequences and complications that negatively affect the health status and significantly worsen the prognosis of the disease.

Consider the main risks of trisomy:

• Pathologies from the cardiovascular system and heart diseases. About 50% of patients have birth defects, which require surgical treatment at an early age.
• Infectious diseases - defects from the immune system provoke an increased sensitivity to various infectious pathologies, especially colds.
• Obesity - people with the syndrome have a greater tendency to being overweight than in the general population.
• Diseases of the hematopoietic system. Downs are more likely to suffer from leukemia than healthy children.
• Short life expectancy - the quality and duration of life depends on the severity of congenital diseases, the consequences and complications of the disease. Back in the 1920s, people with the syndrome did not live to be 10 years old, today the age of patients reaches 50 or more years.
• Dementia - dementia and persistent decline in cognitive activity is associated with the accumulation of abnormal proteins in the brain. Symptoms of the disorder occur in patients under 40 years. This disorder is characterized by a high risk of seizures.
• Stopping breathing in sleep - apnea is associated with an abnormal structure of the soft tissues and skeleton that are susceptible to airway obstruction.

In addition to the above complications, trisomy is characterized by problems with the thyroid gland, weakness of bones, poor eyesight, loss of hearing, early menopause and intestinal obstruction.

Diagnostics of the mosaic Down syndrome

You can detect genetic pathology before birth. Diagnosis of mosaic Down syndrome is based on the study of karyotype of blood and tissue cells. Early in pregnancy, a chorionic biopsy is performed, which reveals signs of mosaicism. According to statistics, only 15% of women who learned about genetic abnormalities in a child decide to leave it. In other cases, abortion is prematurely terminated.

Consider the most reliable methods for diagnosing trisomy:

• Biochemical blood test - the blood is taken from the mother for examination. The biological fluid is evaluated for β-hCG and plasma protein A. In the second trimester, another assay is performed to track the levels of β-hCG, AFP and free estriol. Reduced rates of AFP (a hormone produced by the fetal liver) are highly likely to indicate a disease.

• Ultrasound is performed every trimester of pregnancy. The first allows to reveal: anencephaly, cervical hygroma, determine the thickness of the collar zone. The second ultrasound makes it possible to track heart disease, anomalies in the development of the spinal cord or brain, disorders of the gastrointestinal tract, hearing organs, and kidneys. In the presence of such pathologies, abortion is indicated. The last study, conducted in the third trimester, can reveal minor disorders that can be eliminated after childbirth.

The above described studies make it possible to assess the risk of having a child with a syndrome, but they do not give an absolute guarantee. At the same time, the percentage of erroneous results of diagnostics conducted during pregnancy is low.

[23], [24]

Analyzes

Diagnosis of genomic pathology begins in the period of gestation. Analyzes are performed in the early stages of pregnancy. All studies for trisomy are called screening or screening. Their dubious results allow one to suspect the presence of mosaicism.

• First trimester - up to 13 weeks of analysis for hCG (human chorionic gonadotropin) and protein RAPP-A, that is, substances released only by the fetus. In the presence of the disease, hCG is increased, and the level of PAPP-A is lowered. With such results, amniascopy is performed. From the uterine cavity pregnant through the neck are extracted tiny chorionic particles.

• The second trimester - analyzes for hCG and estriol, AFP and inhibin-A. In some cases, the study of genetic material. For his fence, the uterus is pierced through the abdomen.

If a high risk of trisomy is established by the results of the tests, the pregnant woman is prescribed a consultation of a geneticist.

[25], [26], [27]

Instrumental diagnostics

To identify intrauterine pathologies in the fetus, including mosaicism, instrumental diagnostics is shown. When suspected of Down's syndrome, screenings are carried out throughout the pregnancy, as well as ultrasound to measure the thickness of the posterior part of the fetal neck.

The most dangerous method of instrumental diagnosis is amniocentesis. This study of amniotic fluid, which is carried out for a period of 18 weeks (sufficient fluid is needed). The founded danger of this analysis is that it can lead to infection of the fetus and the mother, rupture of the bladder and even miscarriage.

Differential diagnosis

The mosaic form of changes in the 21st chromosome requires careful study. Differential diagnosis of Down syndrome is carried out with such pathologies:

• Klinefelter's syndrome
• Shereshevsky-Turner Syndrome
• Edwards Syndrome
• Syndrome de la Chapelle
• Congenital hypothyroidism
• Other forms of chromosomal abnormalities

In some cases, mosaicism on the sex chromosomes XX / XY leads to true hermaphroditism. Differentiation is also necessary for gonad mosaicism, which is a particular case of organ pathology that occurs in the late stages of embryonic development.

Treatment of the mosaic Down syndrome

Therapy of chromosomal diseases is impossible. Treatment of mosaic Down syndrome is lifelong. It is aimed at the elimination of malformations and concomitant diseases. A person with this diagnosis is under the control of such specialists: pediatrician, psychologist, cardiologist, psychiatrist, endocrinologist, oculist, gastroenterologist and others. All treatment is aimed at social and family adaptation. The task of parents is to teach the baby full self-service and contact with others.

Treatment and rehabilitation of downs consists of such procedures:

• Massages - the muscular system, both infant and adult with this syndrome is not sufficiently developed. Special gymnastics helps restore muscle tone and maintain them in a normal state. Special attention is paid to hydromassages. Swimming and water gymnastics improve motor skills, strengthen muscles. Popular use of dolphin therapy, when the patient swims with dolphins.
• Dietitian advice - patients with trisomy have problems with being overweight. Obesity can provoke various disorders, the most frequent are disorders of the cardiovascular system and the digestive tract. The nutritionist gives recommendations on nutrition and, if necessary, prescribes a diet.
• Consultations of the speech therapist - for mosaicism, as well as for other types of syndrome, are characterized by disruptions in the development of speech. Classes with a speech therapist will help the patient correctly and clearly express their thoughts.
• Special training program - children with the syndrome lag behind in development from peers, but they are trained. With the right approach, the child can learn basic knowledge and skills.

Patients are shown general restorative therapy, very often prescribed psychostimulants, neurometabolic and hormonal drugs. It is also necessary to regularly take vitamins. All medication therapy is combined with medical-pedagogical correction. Congenital pathologies and complex diseases require surgical intervention.

Prevention

To date, there are no reliable methods for preventing genetic diseases. Prevention of mosaic Down syndrome consists of such recommendations:

• Timely treatment of any disease and a healthy lifestyle. Increased activity improves blood circulation, protecting eggs from oxygen starvation.
• Proper nutrition and normal weight. Vitamins, minerals and other nutrients not only strengthen the immune system, but also maintain hormonal balance. Excess weight or excessive leanness breaks the hormonal balance, and provokes malfunctions in the maturation and development of sex cells.
• Preparation for pregnancy. A couple of months before the planned conception, you need to go to a gynecologist and start taking vitamin and mineral complexes. Special attention should be paid to folic acid, vitamins B and E. They normalize the work of the genital organs and improve metabolic processes in the sex cells. Do not forget that the risk of giving birth to a child with deviations increases in couples where the age of the future mother is more than 35 years, and the father is more than 45.
• Antenatal diagnosis. Analyzes, screenings and a number of other diagnostic procedures performed during pregnancy, can reveal serious violations in the fetus and decide on further bearing or abortion.

But even the implementation of all preventive measures can not give a 100% guarantee for the birth of a fully healthy baby. Trisomy is a random genetic abnormality, from which no woman is insured.

[28], [29], [30]

Forecast

Mosaic Down syndrome has a more positive outcome, in contrast to the classical form of pathology. The prognosis is due to the fact that healthy cells partially compensate for the genetic defect. But the child will still have external signs of trisomy and a characteristic lag in development. But the survival rate of such patients is much higher, they have less frequent developmental anomalies that are incompatible with life.

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Famous people with a mosaic form of Down syndrome

Changes in the 21st chromosome lead to irreversible consequences that are not amenable to treatment. But, despite this, among those born with trisomy there are artists, musicians, writers, actors and many other accomplished personalities. Famous people with a mosaic form of Down's syndrome boldly declare their illness. They are a vivid example of the fact that if you want you can cope with any problem. The genomic disorder is for such celebrities:

• Jamie Brewer is an actress, known for her role in the series American Horror Story. The girl is not only a movie star, she is also a model. Jamie participated in the show Mercedes-Benz Fashion Week in New York.

• Raymond Hu is a young artist from California, USA. The peculiarity of his paintings is that he paints them according to the ancient Chinese technique: on rice paper, watercolor and ink. The most popular work of a guy is portraits of animals.

• Pascal Duquenne is an actor, winner of the silver award of the Cannes Film Festival. Became famous for his role in the film Jacques Bath Dormel's "Day of the Eight."

• Ronald Jenkins is a world-famous composer and musician. His love of music began with a gift - a synthesizer, received in his childhood for Christmas. To date, Ronald is rightfully considered a genius of electronic music.

• Karen Hafnii - assistant teacher, athlete. The girl is engaged in swimming and participated in the marathon on the English Channel. She became the first person with a mosaicism, which swam 15 km at a water temperature of + 15 ° C. Karen has his charitable foundation, which represents the interests of people with chromosomal pathologies.
• Tim Harris is a restaurateur, the owner of "the friendliest restaurant in the world." In addition to a delicious menu, Tim's establishment offers free hugs.

• Miguel Tomasin is a member of the Reynols group, a drummer, a guru of experimental music. The guy plays both his songs and covers of famous rock musicians. He is engaged in charity, performs in the centers and at concerts to support sick children.

• Bogdan Kravchuk is the first person in Ukraine with Down syndrome who entered the university. The guy lives in Lutsk, is fond of science, has many friends. Bogdan entered the East European National University after Lesya Ukrainka at the Faculty of History.

As practice shows and real examples, despite all the complications and problems of gene pathology, with the correct approach to its correction, it is possible to grow a successful and talented child.

[32], [33]