Down's disease
The peculiar form of oligophrenia was described by L. Down in 1866. The author noted a sharp decrease in intelligence, combined with the characteristic appearance of people and various developmental malformations. The first description of Down's disease in Russia was made by PI Kovalevsky in 1905. Among the mentally retarded children, 10% suffer by Down's disease .Both sexes are affected approximately at the same frequency.
With Down's disease, a variety of malformations are found. The nature of the vices and their distribution differ markedly from the nature and frequency of vices in the population. An analysis of deceased children with Down's disease showed the presence of congenital heart defects and major vessels in 67% of cases. Almost all vices of the cardiovascular system with Down's disease are accompanied by defects in the development of other organs and systems. Often they are accompanied by malformations of the digestive system. On the part of the genitourinary system, the following defects were noted: congenital ureteral enlargement, enlargement or narrowing of the ureter, lobar kidneys, polycystosis, and absence of kidneys. In some cases, the absence of lungs, absence or underdevelopment of lobes of the lungs. There was a decrease in the brain in size, underdevelopment of the frontal lobes, furrows and gyri, and various abnormalities of the blood vessels of the brain are often formed. The ventricles of the brain are often underdeveloped, their cavities reduced. Nerve cells are not sufficiently developed. Often there are combined developmental malformations of various organs and systems, multiple congenital malformations.
The disease is usually recognized at birth: the child's weight is usually below normal, children are sluggish, poorly sucked, crying is weak. Of the most common signs, one should note the irregular shape of the skull, the oblique incision of the eyes, the semilunar fold of the skin in the angle of the eye( near the nose), the high palate, small ears and their low position. Characteristic disproportion of the trunk and extremities. Hands have a peculiar structure - short fingers, curved and shortened little finger. Often expressed a transverse skin fold in the palm of your hand. Attention is drawn to the marked decrease in muscle tone, the absence of certain reflexes. Reducing muscle tone is an important sign of Down's syndrome, especially during the period of newborns. Children suffering from Down's disease develop with a gross delay in motor and mental functions. The anomalies of the physical structure in the older age are of the same type and concern, first of all, the bone system. The figure of such children is squat, the limbs are short, the shoulders are lowered, the head is tilted forward. The brachycephalic shape of the skull( the predominance of the transverse head size), the oblique occiput, the underdevelopment of the bones of the nose and upper jaw, and the lower jaw protrude almost always. You can often notice a variety of abnormalities of the teeth. In radiographic examination of the bone system, finger deformities are detected, especially the fifth finger, osteoporosis and some other characteristic features.
A typical sign of Down's disease is a decrease in intelligence. The vast majority of children are imbeciles( 86%), 10% idiots, 4% -debils. Underdevelopment of speech is noted in all persons with Down's syndrome. Understanding speech is also limited. Any instructions are performed poorly. Vocabulary is poor, includes the names of everyday objects, simple actions and qualities. Speech is characterized by the use of simple phrases: words are pronounced incorrectly, a gross violation of phonetics of hissing and whistling sounds is often found. The logical-grammatical aspect of speech is also rather difficult. Reading and writing are formed with difficulty, the account is performed with difficulty. Children with Down's disease, as a rule, are trained in special schools. They are easily distracted, suggestible, attention and memory are greatly reduced. Mechanical memory prevails over the semantic. Abstract thinking is sharply limited. Children in some cases are taught reading, but it is only mechanical in nature, while the semantic interpretation of the reading is not possible.
The state of the emotional sphere is characterized by a number of features that distinguish Down's disease from other forms of dementia. Attention is drawn to emotional liveliness, the relative safety of emotions in comparison with the depth of an intellectual defect. Children are very attached to close people, they are affectionate, but they differ in mood instability with affective outbursts, unmotivated negativism. With Down's disease, the ability to imitate is well developed. Thanks to this feature, children manage to instill self-service skills.
When examining children in a hospital, the most common are cardiovascular malformations. The frequency of heart defects with Down's disease is 51%.The most frequently detected defects include the triad, tetralogy and pentad of Fallot, hypoplasia of the pulmonary artery, hypoplasia of the aorta, non-healing of the botulinum duct, defects of the interatrial and interventricular septum. Many patients have violations of the endocrine system: obesity, a decrease in basal metabolism, which, apparently, is associated with a decrease in thyroid function.
When examined by a neuropathologist, a violation of fixation of the sight by both eyes on one subject( convergence), convergent strabismus, asymmetry of the face is detected. Often there are violations of the vestibular apparatus, which is manifested involuntary movement of the eyeballs in the horizontal direction, sometimes with elements of circular motion. Most children with Down's disease have mild coordination disorders, unclear coordination tests( for example, when trying to touch the tip of the index finger of an elongated hand to the tip of the nose with closed eyes, etc.).Disorders from the autonomic nervous system are manifested by persistent reddening of the skin with its mechanical irritation( due to the peculiarity of the reaction of the blood vessels of the skin), dry skin, a tendency to dermatitis, dystrophic changes in the nails, increased fragility of the hair.
In 1959, a study of the chromosomal recruitment of 9 children with Down's disease found that 47 cells contained 47 chromosomes. Trisomy on the 21st pair of autosomes( three chromosomes instead of two) was detected in all 9 children examined. Numerous studies by researchers in subsequent years have confirmed that the underlying cause of Down's disease is anomalies in the number of chromosomes, expressed primarily by the presence of one superfluous chromosome from the group of autosomes. Of particular interest is the fact that many of these children are born from mothers over 35 years of age. An analysis of the available data confirmed the dependence of the frequency of Down's disease on the mother's age. The average age of the mother at the time of the birth of a sick child is 33 years.
It is widely believed that the onset of Down's disease is facilitated by "wear of the body", "diseases of the genital area of a woman", "functional aging of the reproductive apparatus, in particular the uterus and the ovum," and other factors. An important fact that can indirectly indicate the possibility of giving birth to a child with Down's disease is the mother's presence of episodes of stillbirths or births of unviable children who died in the early period after birth.
The probability of the birth of a child with Down's disease in mothers of different age groups varies. In women aged 19 to 35, it does not exceed 1 case per 1000 newborns. Starting from the age of 35, the probability of the birth of a sick child is rapidly increasing, reaching between 2 and 40% of the order of 2% or more. The occurrence of an abnormal set of chromosomes with Down's disease can be associated with the violation of certain phases of meiosis. In particular, the fact that the vast majority of children with Down's disease is born to mothers at the age of 35 allows us to link the mechanism of this pathology to the process of egg formation in the woman's body. The process of ovogenesis( the formation of female reproductive cells - oocytes) begins with the intrauterine development of the girl before the onset of ovulation. The longer this period, the greater the probability of damage to the egg. In this case, the impact of various unfavorable environmental factors may have a certain pathological effect. The age criterion, namely the achievement of 35 years, also plays a certain role due to the fact that in this age period the hormonal balance changes in the woman's body. Examination of chromosomal recruitment of parents and close relatives of a child with Down's disease caused by trisomy in 21 autosomes does not reveal any specific anomalies. The risk of re-birth of a sick child in the case of trisomy remains the same as in the population.
Downward translocation syndrome
This syndrome ranks second in frequency after trisomy, described above. Downward translational syndrome occurs in 3.5% of children with Down's disease. The essence of the syndrome is the transfer of a gene or a segment of a chromosome into a new, unusual position for it on the same or another chromosome. Differences in the emergence of manifestations, compared with children with regular trisomy, no. The study of chromosomal recruitment in sick children and their parents is of paramount importance for the determination of this syndrome, since the probability of the birth of a second child with Down's disease in the case of translocation increases dramatically.
13-15 and 21-22 autosomes are involved in translocation. At the same time, the number of chromosomes in the set remains normal and is 46. If a patient has a child of Down's translational syndrome, one of the outwardly normal parents is often the carrier of this mutation. The frequency of the birth of sick children in the mother with translocation is quite high and is 25%.In this case, the probability of the birth of a sick child does not depend on the age of the woman. An insignificant part of sick children is born from the marriage of a healthy woman with a father - a carrier of the mutation. Children with translocation syndrome account for 5% of the total number of children with Down's disease, born to mothers under the age of 30 years. In family cases of Down's disease, translocation modifications of chromosomes are detected in approximately 30% of cases.
Down Syndrome with Mosaicism
A third type of chromosomal abnormality in Down's syndrome is mosaicism, when a normal number of chromosomes is found in some cells, and in others 47 chromosomes( trisomy over the 21st pair of chromosomes).The frequency of mosaicism is about 1% of children with Down's disease.
Manifestations of the disease in the case of Down syndrome with Mosaicism are largely determined by the ratio of normal and pathological cells with three 21 chromosomes. In some cases, people have typical features of Down's disease, in others - signs of the disease are poorly expressed. The intellect of children suffers less than in the first variant of the disease. Suspicion of mosaicism always occurs when a combination of typical external features of Down's disease and a fairly conserved intelligence.
The cause of mosaicism is the non-separation of chromosomes in the early stages of zygotic division, which leads to the formation of two types of cells: one contains 46, and in the other 47 chromosomes. In women with mosaicism, both normal children and patients with the first variant of Down's disease are born.
Among the many changes in Down's disease, a special place is taken by characteristic skin patterns. The cutaneous transverse fold located on the palm, occurs with Down's disease on the left hand in about half the cases. Another sign of trisomy on the 21st pair of chromosomes in the study of skin patterns is the presence of one transverse fold in the place of folds on the little finger instead of two, which are usually noted in the norm. In addition, there are certain changes in the skin pattern of the fingers of the hands, which is determined by dactyloscopy only by a specialist doctor.
Down's disease is accompanied by a change in laboratory parameters of blood and urine. With regular trisomy, the activity of certain enzymes in serum usually increases. The majority of children with Down's disease showed changes in the content of amino acids in the blood and urine. Some children may have an increase in the content of amino acids in the urine. ECG data for Down's disease are of a different nature: from mild conduction disorders to gross heart rhythm disorders.
With Down's disease, long-term treatment with small doses of thyroidin is carried out. Favorable effect is observed in many cases of Down's disease when treated with prephisone( 30 injections per course of treatment).It is reasonable to use niamide and its analogue of noredal, which are psychoanaleptic agents and have an antidepressant effect. The course of treatment with these drugs lasts 2-3 months. With the use of drugs in this group, there may be some side effects, which include: dizziness, headache, increased sweating, etc., but such undesirable effects occur rarely. With liver diseases, the drug niamide is contraindicated. A good effect has drugs that regulate metabolism: nerobol, dianabol, etc., also has a beneficial effect on the diet, composed by the attending physician, taking into account changes in blood and urine tests. It is recommended to use means of general strengthening and stimulating therapy, which include preparations of calcium, iron, aloe. As the child grows, due attention should be paid to teaching basic skills of self-service and practicing with a speech therapist. Communication with the children's team has a beneficial effect on children with Down's disease.
Prevention of Down's disease should be carried out through medical genetic counseling in specialized genetic centers. Such consultations help determine the risk of having a sick child in order to address the issue of abstinence from childbearing in families with a hereditary burden, which occurs with Down's translocation syndrome.
Anomalies of autosomes 13-15 and 16-18.Trisomy syndromes are described for 13-15 pairs of autosomes and 16-18 pairs of autosomes - trisomy. These syndromes have a number of similarities with Down's disease.
The syndrome caused by trisomy for 13-15 pairs of autosomes occurs on average in 1 child of 4,000 newborns. The syndrome is characterized by multiple congenital malformations: small eyes or complete absence of them, hare lip, wolf mouth, six or more fingers, deformities of the skull. There are a variety of heart defects - dextrase, a defect of the interventricular septum, etc. On the part of the gastrointestinal tract, with a careful examination reveals a huge gall bladder, narrowing of the common bile duct, abnormalities of the colon. The developmental defects of other organs can be noted. Often there are umbilical hernias, vascular skin tumors. Many children show a dilatation of the renal pelvis with a large amount of urine accumulated in it, which is caused by the presence of an obstruction to its outflow into the urinary tract( hydronephrosis).Later, a sharp lag in mental development, an increase in muscle tone, often accompanied by convulsive seizures caused by underdevelopment and various abnormalities of brain development.
When studying the chromosome set of children, an extra chromosome of group 13-15 is revealed. In the case of the translocation of these chromosomes, anomalies can be transmitted through an apparently healthy parent. For the emergence of trisomy, the age of the mother may matter. The average age of abortus mothers with trisomy 13-15 chromosomes is 38 years.
The above-mentioned birth defects lead to early death of patients. Most of them( about 70%) die before the age of 3 months. The cause of death is usually heart failure, respiratory failure, aspiration, joining pneumonia.
Trisomy syndrome of 16-18 chromosomes of
This trisomy syndrome occurs somewhat more often compared to the 13-15 chromosome trisomy syndrome. The frequency of this syndrome is approximately 1 case per 3,000 newborns. In girls, this disease occurs 3 times more often than in boys. Children from birth are very small, the cry is weak. Small head sizes, deformations of the skull, protruding occiput, low ears, small lower jaw are detected. Characteristic increase in the number of fingers on the hands and feet, often there are congenital dislocations of the hips. Vascular tumors are often found on the skin. When examining the internal organs, cardiac abnormalities are revealed: a defect of the interventricular septum, an uninfection of the botulinum duct. Also, various abnormalities of the kidneys are determined - the horseshoe kidney, the double ureter, often the testicles are not implanted in the scrotum( in boys), the funnel-shaped anus, the diaphragmatic hernia, the abnormality of the stomach. If children do not die in the first months, with age, deep depression of intellect is formed, increased muscle tone in the legs, frequent convulsions.
When studying the chromosome set, an extra autosome is determined. As with other trisomy, the dependence of the birth rate of sick children on the mother's age is noted. The frequency of trisomy in spontaneous abortions reaches 3%.
The outlook for life is unfavorable. Most children die in the first months of life.
Syndromes due to partial deletion of
autosomes The deletion( loss) of part 4 of the chromosome is manifested by small growth, wolf mouth and hare lip, an inborn defect in the development of the male urethra( the outer opening of the canal opens in the middle or at the root of the genital organ).Changes in the shape of the skull, accumulation in the cavity of the skull of an excessive amount of fluid are found, which leads to an increase in the size of the head, a decrease in the tone of the muscles of the limbs, and mental retardation. Characteristic of various anomalies of the organ of vision and low-lying ears.
Deletion( loss) of part 5 of the chromosome is noted in the syndrome of "screaming cat," so named because the cry of babies resembles a cat's cry. Such children have small growth, reduced size of the brain, at the inner corner of the eye there is a semilunar fold of the skin, the ears are very low, the eyes are widely spaced from each other. Children are characterized by severe mental retardation. In girls this syndrome occurs more often than in boys.
Syndromes of deletion( loss) of a part of the 18th chromosome. The attached syndrome shows reduced brain size, protruding forehead, lack of external auditory canals and hearing loss, a variety of eye anomalies. Individuals with this syndrome have a small growth, are severely lagging behind in mental development, have reduced muscle tone.
Syndrome of loss of part of the 21st chromosome. The syndrome is characterized by severe mental retardation. Some signs of the disease are in many ways the opposite of those with Down's disease: a protruding bridge of nose, low-lying eyelids, large ears, increased muscle tone( a kind of "antidownism").People with this syndrome often have dystrophic changes in bones, an inborn defect in the development of the male urethra( the outer opening of the canal opens in the middle or at the root of the genital organ).In the blood, the number of white blood cells( platelets) can be reduced.