Pathophysiology of Down's Syndrome

Down syndrome is defined as a congenital disorder that occurs because of a chromosomal defect with chromosome 21.  It is the most commonly occurring chromosomal condition according to the National Down Syndrome Society.  Around 6,000 babies in the United States are born with Down syndrome every year.  Worldwide it is estimated to be between 1 in 1,000 to 1 in 1,100 births according to the World Health Organization.  This disorder does not occur more often in certain individuals but instead affects all races and economic levels equally (ndss).  In addition, it doesn’t have a higher chance of affecting someone based on where the person or their family lives and it doesn’t discriminate based on gender.  According to the CDC though, in the United States African Americans born with the disorder have a lower chance of surviving past their first year of life compared with white infants.  The reasons for why African Americans may have a lower chance of survival has not been discovered yet (Weatherspoon). 

Down syndrome is a genetic condition, but it is not normally hereditary.  Often times it is due to a random cell division error during the creation of the father’s sperm or mother’s egg (My Child Without Limits).  The only risk factor that may attribute to an increased risk of a baby being born with Down syndrome is the mother’s age when she gets pregnant.  The risk of a baby being born with Down syndrome increases when the mother is 35 or older.  According to the National Down Syndrome Society, women who are 35 have an increased chance of around 1 in 350 of having a baby who is born with Down syndrome.  The risk increases even more the older the women is when conceiving a child.  At age 40, a woman has a 1 in 100 chance and by age 45, the chances of having a baby with the disorder is 1 in 30.  Although the risks increase with age, around 80% of babies that are born with the disorder are born to moms who are younger than 35.  This is due to a higher fertility rate among the younger generation, women younger than 35 are having more babies than those over 35.  The higher birth rate contributes to the number of babies that are born with Down syndrome to mothers who are at a younger age (Weatherspoon).  

An individual who has Down syndrome is usually diagnosed with the disorder when they are born.  The life expectancy for those born with Down syndrome has increased dramatically though in recent decades.  Due to advancements in treatments, the death rate has fell by roughly 41% from 1979 to 2003 (Weatherspoon).  It has skyrocketed from the average life span being around 25 in 1983, to people living to the age of 60 in recent years (ndss).  Many individuals diagnosed with the disease will exhibit similar physical traits such as small stature, low muscle tone, upward slanting eyes, and a flatted facial profile and nose.  In addition to physical traits, individuals often exhibit intellectual and developmental symptoms as well.  Some of the cognitive impairment problems include impulsive behavior, delayed language and speech development, and a slower rate of learning (NIH).  It is important to understand though that each individual is different, they may exhibit these traits at different degrees and some may not experience these traits at all. 

Diagnosis of Down syndrome occurs both when the baby is in utero and when he/she is born.  Screening tests and diagnostic tests are offered to women of all ages who become pregnant.  Screening tests help to indicate the chances that the baby will be born with Down syndrome.  Based on the screening test, the mother might opt to have diagnostic tests run to diagnose whether the baby actually has the disorder.  Diagnostic tests include chorionic villus sampling and amniocentesis.  Chorionic villus sampling is when fetal chromosomes are analyzed from cells taken from the placenta.  This test normally occurs in the first trimester of a woman’s pregnancy.  The amniocentesis test is taken during the second trimester.  It is when the chromosomes of the fetus are analyzed from a sample of the amniotic fluid.  When the baby is born, the diagnostic test that is used to confirm the diagnosis is a genetic analysis test.  This test includes analyzing the chromosomes in a sample of blood taken from the baby (Mayo Clinic Staff). 

There are three types of Down syndrome that a person can be diagnosed with.  The three different types include trisomy 21 or nondisjunction, mosaicism, and translocation.  Despite which type that individual has, the disorder is caused by the person having an extra portion of chromosome 21 present in some or all of their cells. The presence of the added chromosome 21 alters the DNA causing the individual to have 47 chromosomes rather than the normal 46.  The additional genetic material alters fetal development and causes the characteristics of Down syndrome. The cause of the extra chromosome present in the cells is still unknown.  The additional part of the chromosome can either originate from either the mother’s egg or the father’ sperm.  According to the National Down Syndrome Society, around 5% of Down syndrome cases can be traced back to the father (ndss).  

The first type of Down syndrome is called trisomy 21 or nondisjunction.  This type is the most common out of the three, accounting for 95% of the cases.  Trisomy 21 affects the number of chromosomes within the cells.  It causes three copies of chromosome 21 to be present rather than the normal 2 copies that cells normally have.  This occurs either before or during conception when one of the pairs of chromosome 21 from either the sperm or egg fails to separate.  This results in the embryo having an additional chromosome 21 from either the mother or father.  This extra chromosome is replicated in every cell of the body as the embryo develops.  The presence of the extra chromosome attribute to the individual displaying characteristics of Down syndrome (ndss).

The second type of Down syndrome is called mosaicism or mosaic Down syndrome.  This is the least common type of the disorder, accounting for only 1% of all Down syndrome cases.  Mosaic Down syndrome is when there is a mixture of two types of cells.  Some of the cells in the body contain the normal 46 chromosomes while other cells contain 47 chromosomes.   The cells that contain 47 chromosomes is a result of the extra chromosome 21.  According to research, individuals with this type of Down syndrome may exhibit fewer characteristics of Down syndrome than those with the other two types (ndss).  This may be due to the fact that some of the body’s cells have the normal 46 pairs of chromosomes while only a partial number of cells have the extra chromosome.

The third type of Down syndrome is called translocation.  Translocation occurs in roughly 4% of individuals who are diagnosed with Down syndrome.  It occurs when an extra full or partial copy of chromosome 21 attaches it itself to another chromosome.  Individuals total number of chromosomes in their cells remain 46, but the extra chromosome 21 latches on to chromosome 14 normally.  This extra genetic material from chromosome 21 causes individuals to exhibit characteristics and symptoms of Down syndrome.  Translocation is the only type that has a hereditary factor to it.  There is no hereditary factor in either mosaicism and trisomy 21.  The hereditary factor causes around one-third of the cases of Down syndrome that occurred due to translocation.  This means that around 1% of all Down syndrome cases were caused by a hereditary factor.  The rate of risk of for translocation to occur again is about 10-15% if the mother is the carrier of the gene or around 3% if the father is the carrier (ndss). 

 Down syndrome is not a disorder that is able to be cured by any treatments or medications.  Treatments that are used are often meant to help to decrease the risks of the individual developing additional problems or helping with current problems that accompany Down syndrome.  It is important that treatments are started early in the individual’s life in order to help improve their quality of life.  One complication that many individuals face are developing a heart defect.  Half the children that are born with Down syndrome have some type of congenital heart defect.  This may require the infant to have heart surgery right away after they are born.  Another complication includes developing GI abnormalities in the esophagus, trachea, anus, or intestines.  A third complication is those with Down syndrome are at an increased risk for injury to the spinal cord.  This occurs due to misalignment of the top two vertebrae in the neck, it can cause them to overextend their neck.  Additional complications include a risk for obesity, sleep apnea, immune disorders, seizures, hearing and vision problems, and leukemia (Mayo Clinic Staff).

 A medical treatment that is currently being used aims to affect brain activity to help improve the individual’s ability to learn and understand.  One characteristic that is often associated with those who have Down syndrome is their learning and understanding capabilities is delayed.  Being developmentally delayed signifies a child that is not achieving normal milestones within the normal age range.  It is taking them longer to develop skills that other children have already developed by a certain age.  This makes it important to start treatments and therapy early so that it can help the individual live a more productive life. One treatment involves taking amino acid supplements and a medication called Piracetam.   Piracetam is thought to help improve the brain’s ability to learn and understand.  This medication may be able to help overcome barriers that individuals face who are developmentally slow and help boost their learning capabilities (My Child Without Limits).

Beneficial therapy is often introduced in addition to medical treatments to help improve the individual’s life.  A child with Down syndrome may suffer from a delay in one or more of the developmental milestones.  The five developmental milestones include gross motor skills, fine motor skills, language skills, cognitive skills, and social skills.  There are different types of therapies that aim to help improve these skills to help them live a more productive life.  Three types of therapy that are often used for people with Down syndrome include speech therapy, occupational therapy, physical therapy, and behavior therapy.  Speech therapy is used for children who have developmental delays involving speech and language development.  It is very useful in helping children who may not understand language, have a hard time being able to effectively communicate and other problems involving their speech.  Occupational therapy helps individuals with Down syndrome be able to live their life more independently.  Physical and cognitive disabilities can often make every day activities hard, occupational therapy can help these individuals improve their ability to function in these areas.  Physical therapy can help with balance and coordination for individuals with Down syndrome.  Behavior therapies are often helpful because often times individuals with Down syndrome may be impulsive or act out.  This type of therapy focuses on reducing behavior problems and helps to promote individuals to learn how to adapt to situations (My Child Without Limits).

 Medical research is always being continued in order to help better understand and help treat Down syndrome.  One way that researchers allows researchers to understand more about the disorder is by using an animal model to learn more about Down syndrome.  They have found that there are similarities in mice and human chromosomes, this allows researchers to be able to find and understand potential treatments.  One test that is being tested on mice is administering neuroprotective peptides to mice before they are born.  These peptides are important for brain development and the researchers observed that they allowed the mice to perform learning and memory tasks better as adults.  A second test involves administering the drug memantine to mice.  This drug is currently used in individuals who suffer from Alzheimers disease.  The goal of this drug is to help improve cognitive abilities in young adults (NIH).  There will always be future research to help better understand Down syndrome and find ways to help those with the disorder live longer and more productive lives.

In summary, Down syndrome is a congenital disorder that is caused by cells containing an extra chromosome 21.  It is the most common chromosomal condition occurring in 6,000 babies in the United States a year.  There are three types of the disorder including trisomy 21 which is the most common, mosaicism, and translocation.  Characteristics exhibited by those who have Down syndrome often includes short stature, delayed language and speech, and cognitive impairment.  There is no cure for Down syndrome, but that doesn’t mean that those who have it cannot live a life of quality.  The average life span has increased exponentially from the 1980s and individuals have been living to the age of 60.  Early treatment, along with different types of therapy are key to helping those with Down syndrome live a happy and productive life. 

Works Cited

• Huether, Sue, and Kathryn McCance.  Understanding Pathophysiology.  Elsevier, 2017.
• Mayo Clinic Staff.  “Down syndrome.”  Mayo Clinic, 8 March 2018, https://www.mayoclinic.org/diseases-conditions/down-syndrome/diagnosis-treatment/drc-20355983.  Accessed 24 November 2018.
• My Child Without Limits.  “Down Syndrome Treatment.” MyChildWithoutLimits.org, 2018, http://www.mychildwithoutlimits.org/understand/down-syndrome/down-syndrome-treatment/.  Accessed 24 November 2018.
• ndss.  “Down Syndrome.”  National Down Syndrome Society, 2018, https://www.ndss.org/about-down-syndrome/down-syndrome/.  Accessed 23 November 2018.
• NIH.  “Down Syndrome: Research Activities and Scientific Advances.”  Eunice Kennedy Shriver National Institute of Child Health and Human Development, 21 June 2018, https://www.nichd.nih.gov/health/topics/down/researchinfo/activities.  Accessed 24 November 2018.
• Smith, George F., and Stephen T. Warren. “The Biology of Down syndrome.” Annals of the New York Academy of Sciences 450.1 (1985): 1-9.
• Weatherspoon, Deborah.  “Down Syndrome: Facts, Statistics, and You.”  Healthline, 31, October 2018, https://www.healthline.com/health/down-syndrome/down-syndrome-facts#1.  Accessed 24 November 2018.