The syndrome is named after the British physician John Langdon Down who first gave the description of this condition in 1866. The clinical details of this condition were given in the nineteenth century by Jean Etienne Dominique Esquirol in 1838 and Edouard Senguin 1844. Dr. Jerome Lejeune in 1959 identified that Down syndrome crops up due to trisomy of chromosome 21. The identification of this syndrome in the fetus can be done by chorionic villus sampling or amniocentesis in pregnancy or after the birth of the child. The effects and extent of the extra copy of chromosome 21 vary among individuals and may depend upon the genetic history and pure chance.
The incidence of this syndrome is estimated 1 per 733 births but the statistical data suggest that the incidence increases in case of older parents as the chances of mutation increases in the reproductive cells of such parents. Down syndrome has been reported in other mammalian species like chimpanzees and mice also.
English physician John Langdon Down first identified this syndrome as a kind of mental disability and published a report in 1866 about it. He used the term mongoloid for the children suffering from this syndrome as they have facial similarity with the Blumenbach's Mongolian race. By the 20th century this syndrome became popular as form of mental disability. The sufferers were treated medicines but majority of them either died in infancy or in early adulthood. With the rise of the eugenics movement, 48 states of United States began the sterilization of such individuals and Action T24 in Nazi Germany made the program of systematic murder of such individuals. Until the middle of the 20th century the exact reason for the occurrence of Down syndrome remained unknown but its relationship with the maternal age was noticed very soon. It affects people of all races. Many theories advocated that it is caused by unknown inherited factors while others believed that it is the result of injuries caused at the time of birth.
With the advent of the karyotype techniques in 1950s it became possible to identify the abnormalities associated with chromosome number and shape. In 1959, Jèrôme Lejeune discovered that Down syndrome is the result of presence of an extra chromosome. The extra chromosome was identified as 21 and the condition was named as trisomy. In 1961, 18 geneticists wrote to the editor of The Lancet that term Mongolian idiocy must be changed and it was named as Down syndrome later. In the present scenario the incidence of Down syndrome is estimated at 1 per 800 to 1 per 1000 births. In the United States about 5429 individuals are born by this syndrome as calculated by the Centers for Disease Control and Prevention in 2006. Approximately 95% of these cases crop up due to trisomy of chromosome 21 and it occurs in all races and all economic classes.
Maternal age strongly influences the chances of conceiving a baby with Down syndrome. At maternal age the chance is 1 in 1562, at the age of 35-39 the rate is 1 in 214 and above the age of 45 the chance is 1 in 19. According to a report about 80% of the babies born with Down syndrome belonged to the maternal age group of 35-39. Recent data also suggest that paternal age also influences the chances of occurrence of this syndrome. Fathers with the age group of above 42 are at the risk of giving birth to children with this syndrome. Current research indicates that Down syndrome occurs due to a random event during the formation of sex cells or pregnancy. There is no evidence that whether it is caused due to parental behavior or environmental factors. Individuals suffering from Down syndrome suffer from mild to moderate learning disabilities, developmental delays, low muscle tone in early infancy and characteristic facial features. Some individuals also suffer from heart defects, leukemia, early onset Alzheimer's disease, gastrointestinal troubles and other defects. The symptoms of the syndrome may vary from mild to severe.
Genes present on an extra copy of chromosome 21 are mainly responsible for Down syndrome. As a general rule all human beings contain 23 pairs of chromosomes and all these bear specific genes needed for the proper functioning of all the vital activities of body. All humans inherit 23 chromosomes from the father through sperm and 23 from the mother through egg cell during the act of fertilization but sometimes an extra copy is also inherited from one of the parents. In Down syndrome the offspring generally inherits two extra copies of the chromosome 21 from the mother and one from the father and for this reason the disorder is also known as trisomy 21. About 95% of the persons with this disorder inherit an entire extra chromosome 21.
About 3-4% of the individuals with this syndrome does not inherit the entire extra chromosome 21 but inherit some extra 21 chromosome genes that are generally located on the chromosome 14. This phenomenon is known as translocation and the chances of their occurrence are random for example, if the parent has exactly two copies of chromosomes but some of the genes are also distributed on other chromosomes and if the baby inherits chromosome with extra genes from chromosome 21 then he or she will suffer from Down syndrome. About 2-4% individuals with this disorder inherit additional genes from chromosome 21 and then the condition is identified as mosaic Down syndrome. The percentage of occurrence of mosaic Down syndrome varies and so the individuals do not have typical physical characteristics as found in the individuals with full trisomy 21. Sometimes the symptoms are so mild that this syndrome may remain undetected. If proper genetic testing is not done then this condition may be often confused with trisomy 21.
The exact reason how extra genes on chromosome 21 result in Down syndrome is not yet clear. Scientists believe that the presence of extra gene interfere with the normal functioning of other genes or there are chances that these extra genes may become more active than other genes that may alter some vital functions of body and so resulting in this disorder. Scientists are still working to find out which genes from chromosome 21 are exactly inherited that develop the symptoms of this disorder. About 400 genes have been identified on chromosome 21 but the function of majority of them is not clear. With the help of human studies and animal models scientists are trying to reveal the mystery of these genes. The only known reason why a child with Down syndrome is born is the increased maternal age. The woman who conceives very late is generally at a very high risk of giving birth to a child with this disorder. Parents who have conceived a child with Down syndrome have 1% chance of giving birth to another with this disorder. If a parent is a carrier of a chromosome 21 translocation then the risk of giving birth to a child with this disorder is 100%. A woman suffering from Down syndrome is at 50% risk of giving birth to a child with this syndrome. If the father is suffering from this disorder then the chances of child with this disorder are also increased.
The severity of Down syndrome may vary from mild to severe but the individuals share some widely recognizable features. These features include flattened face and nose, short neck, small mouth with protruding tongue, small ears and small eyes with many folds of skin present at the corner of the eyes. White spots may be identified near the colored part of the eyes. The hands are short with broad and short fingers. The muscle tone is poorly developed with loose ligaments. Growth and development also delayed and height less than average. Many noninvasive screening techniques are now available by which the parents can identify if the chances of a baby with Down syndrome are suspected. This helps the parents to decide the fate of the baby. The prenatal screening tests include expanded alpha-fetoprotein (AFP) screening test, nuchal translucency test and additional ultrasound screens that detect certain important anatomical features of the fetus. These tests give a prediction that there are chances of Down syndrome to occur in the fetus but the results may not be 100% true.
The most widely used test is the expanded alpha-fetoprotein test (AFP). A blood sample of the mother who is pregnant for 15-20 weeks is taken out and examined. The levels of alpha-fetoproteins and three hormones namely unconjugated estriol, human chorionic gonadotropin and inhibin-A are measured in the blood sample. If the levels of these proteins and hormones are elevated then Down syndrome is suspected but cannot be predicted with 100% surety. The nuchal translucency test measures the thickness of the fold in the neck with the help of the ultrasound. This test can be performed within 11-13 weeks of pregnancy. If mother's age is also taken into consideration then this test gives about 80% accuracy of chances of the birth of a chile with Down syndrome.
Women identified with high risk of giving birth to a child with this disorder can be suggested to undergo more ultrasound screens between 18-22 weeks of pregnancy. Some characteristic markers that detect that the child will suffer from Down syndrome are length of long arm or femur, length of nasal bridge, size of renal pelvis, small bright spots in heart and small middle section of the little finger. Other markers include presence of a large gap between the first and the second toe, increased brightness of bowel and widened iliac angle.
The diagnosis of Down syndrome in the fetus can be made before birth but the diagnostic tests carry a small risk of miscarriage. If Down syndrome is suspected after the birth of the child then the diagnosis can be done by using chromosome analysis. Amniocentesis is performed between 16-20 weeks of pregnancy in which a thin needle is inserted into the amniotic cavity through the abdominal wall and a small amount of the amniotic fluid is taken out. This sample is then analyzed to identify chromosomal abnormalities. Chorionic villus sampling (CVS) is another technique that is generally carried out between 11-12 weeks of pregnancy. This test involves collection of the chorionic villus cell sample from the placenta that can be taken out by inserting a needle in the abdominal wall or through a catheter in the vagina.
The chromosomes collected in the sample are checked for abnormalities. Percutaneous umbilical blood sampling (PUB) can be carried out where the fetal blood sample can be collected from the umbilical cord by the insertion of needle in the abdominal wall and then the sample is analyzed for abnormalities. This test is generally performed after 18 weeks of pregnancy.
Cognitive impairment is the most common condition associated with Down syndrome. The process of cognitive development in such individuals is generally delayed and the symptoms may vary from mild to severe as they find difficulty in learning things. How trisomy of chromosome 21 leads to cognitive impairment is still a mystery. Scientists have found that the average brain size of a person with this disorder is generally small and certain areas of brain especially the hippocampus and the cerebellum also show alterations in their normal functioning. Defect in hippocampus results in impairment of learning and memory formation. Scientists are tirelessly working to find out which genes are present on the chromosome 21 that result in cognitive impairment. The other health problem associated with Down syndrome is congenital heart defect. Majority of the individuals born with this syndrome generally suffer from atrioventricular septal defect. Other heart defects that can be coupled with this disorder are ventricular septal defect, atrial septal defect, tetralogy of Fallot and patent ductus arteriosus. Some babies are suggested to undergo immediate heart surgery soon after their birth in order to cure these heart defects.
Gastrointestinal troubles are also associated with Down syndrome and they commonly include esophageal atresia, tracheoesophageal fistula, duodenal atresia, Hirschsprung disease and imperforate anus. Individuals suffering from Down syndrome are at higher risk of getting infected with celiac disease. Sometimes surgery is required to get rid of these problems. Certain kinds of cancer are very frequently found in individuals suffering from Down syndrome for example, acute lymphoblastic leukemia, myeloid leukemia and testicular cancer. Solid tumors rarely make their appearance in such individuals. Other conditions that can also arise in individuals with this disorder are hearing loss, frequent ear infections, hypothyroidism, cervical spine instability, visual impairment, obesity, constipation, infantile spasms, dementia and early-onset Alzheimer's disease. About 18-38% of the individuals with this disease also suffer from behavioral defects like attention deficit hyperactivity disorder (ADHD), depression and stereotypical movement disorders.
In the present context although the genetic cause of Down syndrome is known but there is no possible cure for this disorder. Scientists are continuously working to find out the mystery of the genes responsible for this disorder but it will take some more years to solve this riddle. Corrective surgery to cure heart defects, gastrointestinal problems and other health issues is mandatory in case of some individuals. Regular health checkup is required in order to keep a track over hearing aids, hypothyroidism, visual impairments, obesity, ear infections and other medical conditions.
Such individuals should be fully welcomed in the family and community. It is very important that proper care of the children suffering from Down syndrome must be taken and they must be stimulated, encouraged and educated from their childhood. Physical therapy, occupational therapy and speech therapy are very beneficial for the treatment of such children. Children with Down syndrome are able to learn like normal children and if they are encouraged they give good results also. Social development and social learning of such children are generally normal but the motor skills, speech and language associated features are delayed.
Adults with Down syndrome attain same hormonal changes during puberty like the normal individuals. Girl with this disorder have normal menstrual cycle although they are less fertile and may also become pregnant. Males have low sperm count but can become fathers. Proper education of such individuals about sexual development and contraception is very important. Individuals with this disorder generally live normally and with proper support they enjoy life, relationships and work. Such adults generally undergo ageing faster than normal individuals. As they grow old the risk of memory impairment, hypothyroidism and dementia increases.
By the age of 40 these individuals show signs of dementia and early onset of Alzheimer's disease. By the age of 60 about 50-70% of the individuals develop Alzheimer's disease. The reason why the individuals with Down syndrome age prematurely and develop Alzheimer's disease is not known. Since individuals with this disease have three copies of chromosome 21 and the genes present on these chromosomes generally increase the chances of onset of Alzheimer's disease. Although many individuals with Down syndrome get paid employment while others remain unemployed and those who wish to do job are provided adequate training.
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