Down disease is a disease caused by the chromosomal aberration of the 21st pair of chromosomes, manifested by a number of physical defects, often dementia and a sharp decrease in resistance to infectious diseases.
Etiology and pathogenesis of Down disease
The etiology and pathogenesis of Down disease over the years has not been clarified. It was assumed that the basis of the disease is polyglandular insufficiency, that is, a dysfunction of several endocrine glands (thyroid, pituitary, etc.), a sharp lag in the development of the central nervous system. In 1959, it was found out that most often (in 94% of cases) there is trisomy of the 21st pair of chromosomes in Down syndrome. Such a violation of the karyotype (trisomy) can be met during the maturation of the germ cell, when the 21st pair of chromosomes non-diverge occurs and an egg cell containing 24 chromosomes was formed under the influence of often unknown causes. When such an egg is fertilized by a normal spermatozoon containing 23 chromosomes, a child with 47 chromosomes develops, namely Down disease. Children with this disease, which contain 47 chromosomes in the karyotype, are born mainly among elderly mothers.
In some cases, patients (3–5%) have a karyotype with 46 chromosomes, and some of them (usually in the 13th – 15th or 22nd pair) have an extra 21st chromosome (46 chromosomes with translocation), and mosaic transmutations, chromosomal translocations – 13-15 / 21, 21/22, 2/21, 4-5/21, 20/21. Sick children with such a karyotype are predominantly born among young mothers who carry the same translocation and have only 45 chromosomes. Usually chromosomal aberration can be inherited from previous generations. Clinical differences in the course of Down disease in trisomy or translocation of chromosomes are established. When the disease forms are erased, a mosaic karyotype is established, with some of the cells containing a normal karyotype, and some of the cells – an extra 21st chromosome.
The question of the causes of chromosomal aberrations responsible for the development of Down disease is not fully understood. Children with Down syndrome are usually born the last in a series of brothers and sisters. The mother, both before and after the birth of a child with Down syndrome, has an increased frequency of spontaneous miscarriages and stillbirths. If fraternal twins are born, then the presence of Down disease is usually inherited by one of them; in the case of the birth of identical twins, Down syndrome is observed among both. In the onset of Down disease, apparently, deep mental trauma and starvation of the mother are important. It was found that women after many years in the fascist concentration camps gave birth to relatively more children with Down syndrome. Chromosomal aberrations can also be caused by a number of known mutagenic factors – ionizing radiation, chemical, thermal effects, etc.
Clinical signs that allow to diagnose a disease, in typical cases, are detected at the earliest stages of a child’s life: the small growth of the child, a small round head with a sloping nape, a peculiar face – poor facial expression, an oblique incision of the eyes with a fold at the inner corner (epicanthus), a wide flat bridge of nose, small deformed ears, attract attention. The mouth is usually half-open, the tongue is thick, unwieldy, the palate is high, the lower jaw sometimes protrudes anteriorly. Dry eczema is often observed on the cheeks, as a result of which they are hyperemic. Shortening of the limbs is found, especially in the distal regions. The hand is flat, fingers are wide, short. The little finger is shortened, often crescent warped medially. Often there is a large gap between the I and II toes. There is a peculiar pattern of skin folds on the palms. Normally, among the numerous folds in the palm, the three largest ones stand out – one of them is surrounded by a raised thumb in the form of an arc, the other two cross the palm in the transverse direction. In case of Down disease, both transverse folds merge and form one transverse, going through the whole palm. It can be on both hands, but more often well expressed on one. The fountain springs are very large at birth and close late. There is a third spring on the crown. There is muscular hypotonia among such children.
In physical development, children are in arrears. Neuropsychic development is significantly slowed down. They start to hold their heads up late (usually not earlier than 6 months), sit down and stand. They have late and poorly developed speech. Often between the ages of 2 and 6, they pronounce only a few words, the vocabulary is small. Later, the children utter individual short phrases, but they usually never have a coherent speech.
With age, a number of new symptoms of the disease are revealed. The voice is getting rough. There are myopia, strabismus, frequent to conjunctivitis and blepharitis, depigmentation foci on the periphery of the iris (white spots); hypertrophy of the papillae of the tongue, improper growth of teeth, caries. There are anomalies of the structure of the sternum, sometimes asymmetrical arrangement of the nipples. The navel always protrudes above the skin. Epicanthus disappears with age, hypotension can increase.
Mental retardation in case of Down disease is characterized mainly by imbecility of various degrees, however, moronity and idiocy are sometimes observed. Some children can be taught to read and write, but, as a rule, they cannot count. Children with Down syndrome are affectionate, good-natured, obedient, but at times stubborn. They have an amazing ability to imitate, but absolutely can not adapt to any systematic work. There is a lag in sexual development.
In children with Down disease in 30 – 40% of cases congenital heart and vascular defects (non-union of the oval opening, ventricular septal defect, etc.) are detected. In some cases, there are malformations of the intestines or others.
Infectious diseases are extremely difficult and have often led to death in the past.
Children with Down syndrome are 15 times more likely than other children to have acute leukemia. There is evidence of a combination of congenital leukemia and Down disease. Sometimes there are leukemoid reactions that are mistakenly diagnosed as leukemia.
The karyotype of patients with acute leukemia is characterized by the appearance of additional chromosomes (47 or 48), fragmentation or translocation, the presence of the Philadelphia – a small acrocentric chromosome (Ph) of the 21st pair. When leukemia is combined with Down disease, aneuploidy is intermittent. It is assumed that the 21st chromosome has the gene loci responsible for leukopoiesis.
Down disease diagnosis
Diagnosis in typical cases is based on clinical examination data. A change in the karyotype confirms the diagnosis of the disease.
The prognosis depends on the form of the disease, the frequency and severity of intercurrent infections.
Down disease treatment
Attempts to treat Down’s disease were not crowned with great success. At the same time, complex therapy, including the proper organization of the regimen, rationally constructed medicopedagogical work, physiotherapy exercises and massage, along with the inclusion of drugs, sometimes has some therapeutic effect.
Syndromes due to partial deletion of autosomes
With partial deletion of the short arm of the 4th autosome (4p -), patients have short stature, cleft lip and palate, hypospadias, hydrocephalus, muscle hypotension, mental retardation, coloboma of the iris, low location of the auricles. In the syndrome “cri du chat” (“cat’s cry”), a deletion of the short arm of the 5th chromosome is observed (5p -). The syndrome is characterized by the following features: short stature, microcephaly, epicanthus, low ear placement, hypertelorism, mental retardation. The most characteristic symptom is a special mournful, “meowing” cry at an early age. The syndrome of partial deletion of the short arm of the 18th autosome is clinically manifested by microcephaly, eye abnormality, atresia of the external auditory passages, hearing loss, short stature, mental retardation, muscle hypotension. The syndrome of partial deletion of the long arm of the 18th autosome (18q -) is characterized by microcephaly, occasionally cyclopia, physical and mental retardation, deformation of the auricles, spindle-shaped fingers, etc. In the syndrome of partial deletion of the 21st chromosome, mental retardation, anti-Mongoloid face type (protruding bridge of the nose, large, low-lying ears), muscle hypertension, dystrophic bone changes, hypospadias, thrombocytopenia are observed.