Why the world turns its focus on Down Syndrome?

The world’s attention will once again be focused on Down Syndrome with international healthcare organizations, governmental agencies, and communities turning their time to observe Down Syndrome Day on March 21. Down Syndrome is a genetic disorder caused by the presence of all or a portion of a third chromosome 21.

Patients typically present with mild to moderate intellectual disability, growth retardation, and characteristic facial features.  This syndrome was first described by an English physician, John Langdon Down, in 1866, but its association with chromosome 21 was established almost 100 years later by Dr Jerome Lejeune in Paris. It is the presence of all or part of the third copy of chromosome 21 that causes Down syndrome, the most common chromosomal abnormality occurring in humans.  It is also found that the most frequently occurring live-born aneuploidy is trisomy 21, which causes this syndrome. The majority of patients with Down syndrome have an extra copy of chromosome 21. There are different hypotheses related to the genetic basis of Down syndrome and the association of different genotypes with the phenotypes. Among them is gene dosage imbalance, in which there is an increased dosage or the number of genes of Hsa21, which results in increased gene expansion. It further includes the possibility of association of different genes with different phenotypes of Down syndrome.  Down Syndrome Critical Regions (DSCR) is a few chromosomal regions that are associated with partial trisomy for Has21. After a thorough study of different analyses, it became clear that a single critical region gene cannot cause all the phenotypical features associated with trisomy 21, rather it is more evident that multiple critical regions or critical genes have a role to play in this phenomenon. The incidence of Down syndrome increases with maternal age, and its occurrence varies in different populations (1 in 319 to 1 in 1000 live births. The occurrence of other autosomal trisomy is much more common than the 21, but the postnatal survival is very poor as compared to Down syndrome. This high percentage of survival of patients with trisomy 21 is thought to be a function of a small number of genes on chromosome 21 called Hsa21, which is the smallest and least dense of the autosomes. An extra copy of chromosome 21 is associated with Down syndrome, which occurs due to the failure of chromosome 21 to separate during gametogenesis, resulting in an extra chromosome in all the body cells. Robertsonian translocation and isochromosome or ring chromosome are the other two possible causes of trisomy 21. Isochromosome is a condition when two long arms separate together instead of the long and short arms while in Robertsonian translocation. This occurs in two to four percent of the patients. The long arm of chromosome 21 is attached to another chromosome, mostly chromosome 14. In mosaicism, there are two different cell lines because of the error of division after fertilization. Different clinical conditions are associated with Down syndrome as different systems are affected by it. These patients have a wide array of signs and symptoms like intellectual and developmental disabilities or neurological features, congenital heart defects, gastrointestinal (GI) abnormalities, characteristic facial features, and abnormalities. Congenital cardiac defects are by far the most common and leading cause associated with morbidity and mortality in patients with Down syndrome, especially in the first 2 years of life. The incidence of CHD in babies born with Down syndrome is up to 50 percent. The most common cardiac defect associated with Down syndrome is an atrioventricular septal defect (AVSD), and this defect makes up 40 percent of the congenital cardiac defects in Down syndrome. The second most common cardiac defect in Down syndrome is a ventricular septal defect (VSD), which is seen in about 32 percent of patients with Down syndrome. Together with AVSD, these account for more than 50 percent of congenital cardiac defects in patients with Down syndrome. There is geographical variation in the prevalence of the cardiac defect in Down syndrome, with VSD being the most common in Asia and secundum type ASD in Latin America. The reason behind this difference in the prevalence of different types of CHD in different regions is still unclear. Patients with trisomy 21 have many structural and functional disorders related to the GI tract. Structural defects can occur anywhere from the mouth to the anus, and it has been found that certain defects like duodenal and small bowel atresia or stenosis, annular pancreas, imperforate anus, and Hirschsprung disease occur more commonly in these patients as compared to the general population. Patients with Down syndrome are ten times more at risk of developing leukaemia which constitutes about two percent of all paediatric acute lymphoblastic leukemia and 10 percent of all paediatric acute myeloid leukemia. Thirty percent of Down syndrome patients with acute lymphoblastic leukemia have an association with function mutation in the Janus Kinase 2 gene. Five percent to 13 percent of children with Down syndrome have seizures, out of that, 40 percent will have seizures before their first birthday, and in these cases, the seizures are usually infantile spasms. Down syndrome children with infantile spasms do respond better to antiepileptics as compared to other kids with the same, and therefore, early intervention and treatment improve the developmental outcome. Forty percent of patients with Down syndrome develop myoclonic seizures in their first three decades. Dementia occurs more commonly in patients older than 45 years of age with Down syndrome, and about 84 percent are more prone to develop seizures. The seizures in these patients are related to the rapid decline in their cognitive functions. The risk of developing early-onset Alzheimer’s disease is significantly high in patients with Down syndrome with 50 to 70 percent of patients developing dementia by the age of 60 years. Nearly all patients with Down syndrome have mild to moderate learning disability. Thyroid gland dysfunction is most commonly associated with Down syndrome.  The insulin-like growth factor is also said to be responsible for the delay in skeletal maturation and short stature in patients with Down syndrome. Development of surgical techniques for the correction of congenital disabilities, and improvement in general care, has seen a tremendous increase in the survival of infants and the life expectancy of patients with Down syndrome. A study done almost 60 years ago showed that 45 percent of infants survived the first year of life, and only 40 percent would be alive at five years.  A later study conducted about 50 years after that showed that 78 percent of patients with Down syndrome plus a congenital heart defect survived for one year, while the number went up to 96 percent in patients without the anomalies.  This rise in the life expectancy of these patients should continue to rise significantly because of the developments in medical science. Healthcare facilities aim to provide proper and timely management to these patients and to help them to have a fulfilled and productive life. The management of patients with Down syndrome is an interprofessional work. Newborns with suspicion of Down syndrome should have a karyotyping done to confirm the diagnosis. The family needs to be referred to the clinical geneticist for genetic testing. Parental education is one of the foremost aspects regarding the management of Down syndrome, as parents need to be aware of the different possible conditions associated with it so that they can be diagnosed and treated appropriately.

Treatment is symptomatic, and complete recovery is not possible. While life span has increased over the past three decades, these individuals still have a shorter life expectancy compared to healthy individuals. Adequate access to health care, early intervention programs, and inclusive education, as well as appropriate research, are vital to the growth and development of the individual. In December 2011, the UN General Assembly declared 21 March as World Down Syndrome Day, with effect from 2012. To raise public awareness of Down syndrome, the UN General Assembly invites all member-states, relevant organizations of the UN system, and other international organizations, as well as civil society, including non-governmental organizations and the private sector, to observe World Down Syndrome Day properly. The estimated incidence of Down syndrome is between 1 in 1,000 to one in 1,100 live births worldwide. Each year, approximately 3,000 to 5,000 children are born with this chromosome disorder. International days are occasions to educate the public on issues of concern, to mobilize political will and resources to address global problems and to celebrate and reinforce achievements of humanity.

Source: Physics.Org

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