What Causes Down Syndrome? By Aaroah Sunil

What is Down's Syndrome

Down's syndrome is defined as a disease that comes about because of a genetic abnormality that negatively affects the mental capabilities and physical features of an affected person. Individuals with this condition quite often experience varying degrees of medical and physical issues. Some people with the disease are able to successfully lead moderately regular lives while others need persistent medical care. It affects 1 in 800 newborns and is said to be more common with older mothers. The disease cannot be prevented, however it can be discovered in utero, before the baby is born. There is still much controversy in relation to the ramifications of genetic testing for Down'ssyndrome. It has been observed that an estimated 90-93% of pregnancies with a Down's babies were aborted once this was identified through various forms of genetic testing methods.

The outlook for children with Down's syndrome has significantly improved in recent years. The regular life span for an individual with Down's syndrome was 25 years old in the 1980's it has now risen to 49 years of age in present times. People with the disease will usually be infertile especially males who are only partially fertile in extremely rare instances. Most children with Down's syndrome will also experience noticeably reduced cognitive abilities. However, with needed medical intervention, family support and vocational training the child with down syndrome can learn to overcome, to some extent, his or her disabilities.

What Causes Down's Syndrome

The disease as mentioned before is caused by a genetic irregularity. A normal person will have 46 chromosomes, 23 of which will be inherited from either parent. In an individual with Down's syndrome he or she will have an overall number of 47 chromosomes or essentially 1 more chromosome than is expected. This chromosomal abnormality manifests because of an extra copy of the 21st chromosome. The effect of the extra copy will vary among affected people.

The condition cannot be prevented and is said to be a randomly occurring event. However women over the age of 35 are at an increased risk of conceiving a child with Down syndrome. The risk for different age groups are listed below:

o Women who are 25 years of age will typically have a 1in 1,250 chance of having a Down's baby.

o Women who are 30 years of age will normally have. 1 in 1000 chance of having a Down's baby.

o Women who are 35 years of age will normally have 1in 400 chance of having a Down's baby.

o Women who are 40 years of age will typically have 1 in 100 chance of having a Down's baby.

o Women who are 45 years of age will normally have. 1 in 30 chance of having a Down's baby.

The odds of conceiving a child with Down's Syndrome may also be associated with a familial genetic irregularity. A person who has a balanced translocation will not show any signs of down syndrome but will have an elveated risk of conceiving a child with translocation Down syndrome. The estimated risk is 1 in 5 for the female carrier and 1 in 50 for a male carrier. In some cases where there is no unattached copy of chromosome 21 the carrier's offspring will all have Down's Syndrome. The affected parent is therefore said to be a translocation carrier. This sort of Down's syndrome is said to occur in 2-3% of all Down's syndrome cases.

Down Syndrome By Kok Siong Chen

Down syndrome is a common genetic chromosomal syndrome among the population in the world. It is about 1 in 800 liveborns in the population with Down syndrome. This syndrome is starts to be described by a physician named John Langdon Down who published an article in 1866. He stated that there are some children with common characteristics but distinct from other children with mental retardation. He described this syndrome as "Mongoloids". He used this unfortunate name just because of those children looked like people from Mongolia. The "Mongoloids" was dropped from scientific use since 1960s to stop the ethic insult.

About 95% of all patients with Down syndrome have a 47, +21 karyotype. Among these cases there is a small group with familial translocation involving a chromosome 21 and another chromosome with balanced rearrangement. There are some very rare instances of direct transmission of the additional 21 from a Down syndrome mother or father to a Down syndrome child.

Down syndrome patient looks almost alike to each other. We can simply identify the Down syndrome patient by just looking to their physical outlook. However, a confident clinical diagnosis might be difficult early after birth, especially in prematures. Some of the useful diagnostic signs are brachycephaly (flat-head), small ears, Brushfield spots (brown spots on the periphery of the iris) and low iliac and acetabular index in pelvic radiographs. Congenital malformations are frequent in Down syndrome patients too. Thyroid dysfunction is also significantly associated with Down syndrome and might be the cause for developmental delay. Mentally retardation is the most common feature among the Down syndrome patients.

Generally, female menarche occurs at normal time and pregnancies are common among the Down syndrome patients. However, there is hypogenitalism and hypogonadism among the male patients. Therefore, the male with Down syndrome usually is infertile.

In conclusion, Down syndrome patients need to be taken care as there are various specific problems throughout their life. I will write more about the guideline for optimal medical care on these Down syndrome patients later.

What is Down Syndrome? By Jane Orville

Every year, one child in every 800 to 1,000 births will be born with a condition known as Down syndrome. Down syndrome is a disorder in which the child has extra genetic material. This extra genetic material causes the baby to develop differently in the womb. This abnormal development occurs during the early stages of cell division, soon after conception.

There is no known reason for Down syndrome or a cure for it.

The disorder came by its name when an English physician, John Langdon Down, published a description of the characteristics of a person with the condition in 1886. Since Dr. Down was the first person to give the syndrome a name, the disorder is known as Down syndrome.

The Common Forms of Downs

There are three distinct forms of Down syndrome. The most common form is Trisomy 21. This is when a child has an extra chromosome 21.

Instead of having 46 chromosomes in each cell (23 from the father and 23 from the mother), he has 47. Ninety-five percent of children born with Down syndrome have Trisomy 21.

Translocation is another form of Down syndrome and makes up 3 to 4% of the population of people with the disorder. Translocation occurs when part of chromosome 21 breaks off and attaches to another chromosome, changing the genetic makeup. In this form of Down syndrome, each cell has the normal 46 chromosomes, but there is extra genetic material from the broken off chromosome.

The third and final form is called Mosaicism, and is the rarest form of Down syndrome, occurring in only 2% of all cases. Mosaicism happens when some of the cells in the forming embryo have 46 chromosomes, and some have 47. Thus, the alternating pattern gives it the name Mosaicism.

People with Mosaicism may not be as affected with the physical and/or developmentally delayed characteristics of those born with the other two forms of Down syndrome.

Common Physical Traits

Babies with Down syndrome are usually diagnosed at birth or shortly thereafter. Because Down syndrome affects a child physically, there will be certain features that an alert doctor or nurse will pick up on. Most children with the syndrome will have some or all of these traits.

Among the most common physical characteristics are:

o Low muscle tone

o Small nose and flat nasal bridge

o An upward slant to the eyes (almond shaped)

o Small skin folds on the inner corner of the eyes

o Tongue large for size of child's mouth

o Small, sometimes abnormally shaped ears

o A single crease across the center of the palm

o Fifth finger, the pinky, has only one crease instead of two

o Larger than normal space between the large and second toe

o Joints are hyper flexible, able to extend greater than average

These physical traits are characteristic of a baby with Down syndrome, but in order to determine if a child does indeed have the disorder, a chromosome analysis will need to be performed.

This is done by taking blood from your baby and the analysis will be done in a laboratory. Your doctor will notify you of the results.

The Down Syndrome By Francesco Zinzaro Platinum

The clinical features of Down syndrome had been described over a century ago. Even though the underlying cause-an extra copy of chromosome 21-has been recognized for more than four decades, the almost total DNA sequence of chromosome 21-some 33,546,361 base pairs-was determined only 4 many years ago, and also the romantic relationship of genotype to phenotype is just beginning to become understood.

Down syndrome is broadly representative of aneuploid problems, or those that are caused by a deviation in the normal chromosome complement (euploidy). Chromosome 21, which contains just a little less than 2% of the total genome, is among the acrocentric autosomes (the others are 13, 14, 15, and 22), which means one in which almost all of the DNA lies on one side of the centromere. Generally, aneuploidy might include part or all of an autosome or sex chromosome.

Most individuals with Lower syndrome have 47 chromosomes (ie, a single additional chromosome 21, or trisomy 21) and are born to parents with regular karyotypes. This kind of aneuploidy is generally brought on by non-disjunction throughout meiotic segregation, which signifies failure of two homologous chromosomes to separate (disjoin) from each other at anaphase.

In contrast, aneuploid problems that affect component of an autosome or sex chromosome should at some point involve DNA breakage and reunion. DNA rearrangements are an infrequent but important trigger of Lower syndrome and are generally evident as a karyotype with 46 chromosomes by which one chromosome 21 is fused via its centromere to an additional acrocentric chromosome.

This abnormal chromosome is described like a robertsonian translocation and can occasionally be inherited from a carrier parent. Thus, Down syndrome may be brought on by a range of different karyotypic abnormalities, which have in common a 50% improve in gene dosage for almost all from the genes on chromosome 21.

Down syndrome occurs approximately as soon as in each and every 700 reside births and accounts for around one third of all cases of mental retardation. The likelihood of conceiving a child with Lower syndrome is related exponentially to growing maternal age group. However, screening programs detect most lower syndrome pregnancies in pregnant ladies older than 35 years.

This truth, combined using the inverse relationship of maternal age group to overall birth rate, means that most children with Down syndrome are now born to women younger than 35 many years. The condition is usually suspected within the perinatal time period in the presence of characteristic facial and dysmorphic functions this kind of as brachycephaly, epicanthal folds, small ears, transverse palmar creases, and hypotonia.

Approximately 50% of affected kids have congenital heart defects that arrive to medical attention within the immediate perinatal period because of cardiorespiratory difficulties. Strong suspicion from the situation on clinical grounds is generally confirmed by karyotyping inside 2-3 days.

An excellent numerous minor and main abnormalities happen with increased frequency in Down syndrome, yet two impacted individuals hardly ever have the exact same set of abnormalities, and several single abnormalities can be observed in unaffected individuals.

For example, the occurrence of the transverse palmar crease in Down syndrome is about 50%, ten times that within the common populace, however most people in whom transverse palmar creases are the only unusual feature do not have Lower syndrome or any other genetic illness.

The organic history of Lower syndrome in childhood is characterized primarily by developmental delay, growth retardation, and immunodeficiency. Developmental delay is generally apparent by 3-6 months of age as failure to attain age-appropriate developmental milestones and affects all aspects of motor and cognitive function.

The mean IQ is in between 30 and 70 and declines with increasing age. Nevertheless, there is a considerable range in the degree of psychological retardation in adults with Down syndrome, and many impacted people can reside semi-independently.

Generally, cognitive skills are a lot more restricted than affective overall performance, and only a minority of affected people are severely impaired. Retardation of linear growth is moderate, and most adults with Lower syndrome have statures 2-3 regular deviations beneath that from the general population.

In contrast, weight development in Lower syndrome exhibits a mild proportionate improve compared with that from the general population, and most adults with Down syndrome are overweight. Although increased susceptibility to infections is a common clinical function at all ages, the nature of the underlying abnormality isn't nicely understood, and laboratory abnormalities can be detected in both humoral and cellular immunity.

Among the most prevalent and dramatic medical functions of Down syndrome-premature onset of Alzheimer's disease-is not evident until adulthood. Even though frank dementia isn't clinically detectable in all adults with Lower syndrome, the occurrence of standard neuropathologic changes-senile plaques and neurofibrillary tangles-is nearly 100% by age 35 years.

The major causes of morbidity in Down syndrome are congenital center illness, infections, and leukemia. Life expectancy depends to a large extent on the presence of congenital heart illness; survival to ages 10 and 30 many years is around 60% and 50%, respectively, for people with congenital heart illness and approximately 85% and 80%, respectively, for people without congenital heart disease.

The advent of molecular markers for various portions of chromosome 21 supplied considerable information about when and how the extra chromosomal material arises in Down syndrome; and also the Human Genome Project has provided a list from the around 230 genes discovered on chromosome 21.

In contrast, a lot much less is recognized about why elevated gene dosage for chromosome 21 ought to produce the medical features of Down syndrome. For trisomy 21 (47,XX+21 or 47,XY+21), cytogenetic or molecular markers that distinguish between the maternal and paternal copies of chromosome 21 can be used to figure out whether the egg or the sperm contributed the extra copy of chromosome 21.

You will find no obvious medical differences between these two kinds of trisomy 21 individuals, which suggests that gametic imprinting doesn't perform a significant part within the pathogenesis of Lower syndrome. If each copies of chromosome 21 carried by each parent could be distinguished, it is usually feasible to figure out regardless of whether the nondisjunction event primary to an irregular gamete occurred during anaphase of meiosis I or meiosis II.

Studies this kind of as these show that approximately 75% of instances of trisomy 21 are caused by an additional maternal chromosome, that approximately 75% from the nondisjunction events (each maternal and paternal) occur in meiosis I, and that both maternal and paternal nondisjunction events improve with advanced maternal age group.

A number of theories have been proposed to clarify why the incidence of Lower syndrome increases with sophisticated maternal age group. Most germ cell improvement in females is completed before birth; oocytes arrest at prophase of meiosis I (the dictyotene stage) during the second trimester of gestation.

One proposal suggests that biochemical abnormalities that have an effect on the capability of paired chromosomes to disjoin usually accumulate in these cells over time and that, without a renewable source of fresh eggs, the proportion of eggs undergoing nondisjunction raises with maternal age group.

However, this hypothesis does not explain why the romantic relationship in between the occurrence of trisomy 21 and sophisticated maternal age group holds for paternal as well as maternal nondisjunction occasions.

An additional hypothesis proposes that structural, hormonal, and immunologic changes that occur within the uterus with sophisticated age produce an environment less capable to reject a developmentally irregular embryo. Therefore, an older uterus will be a lot more most likely to assistance a trisomy 21 conceptus to term regardless of which parent contributed the additional chromosome.

This hypothesis can explain why paternal nondisjunction errors improve with advanced maternal age. Nevertheless, it doesn't explain why the occurrence of Down syndrome resulting from chromosomal rearrangements (see later discussion) does not increase with maternal age group.

These along with other hypotheses are not mutually exclusive, and it's feasible that a mixture of elements is accountable for the relationship in between the occurrence of trisomy 21 and sophisticated maternal age. A number of environmental and genetic elements have been considered as possible causes of Lower syndrome, including exposure to caffeine, alcohol, tobacco, radiation, and the likelihood of carrying a single or a lot more genes that would predispose to nondisjunction.

Although it is hard to exclude all of these possibilities from consideration as minor factors, there is no evidence that any of those factors play a role in Down syndrome. The recurrence risk for trisomy 21 isn't altered significantly by getting had previous impacted kids.

Nevertheless, approximately 5% of Lower syndrome karyotypes have 46 instead of 47 chromosomes consequently of robertsonian translocations that usually include chromosomes 14 or 22. As described, this kind of abnormality is not associated with elevated maternal age group; nevertheless, in about 30% of such individuals, cytogenetic evaluation of the parents reveals a so-called balanced rearrangement this kind of as 45,XX,+t(14q;21q).

Because the robertsonian translocation chromosome can pair with each of its component single acrocentric chromosomes at meiosis, the likelihood of segregation primary to unbalanced gametes is significant, and also the recurrence risk to the parent with the irregular karyotype is a lot higher than for trisomy 21.

Around 1% of Down syndrome karyotypes display mosaicism by which some cells are normal and some irregular. Somatic mosaicism for trisomy 21 or other aneuploid conditions might initially arise either pre- or postzygotically, corresponding to nondisjunction in meiosis or mitosis, respectively.

In the former situation (one in which a zygote is conceived from an aneuploid gamete), the additional chromosome is then presumably lost mitotically in a clone of cells during early embryogenesis. The variety of phenotypes observed in mosaic trisomy 21 is excellent, ranging from slight psychological retardation with subtle dysmorphic functions to "typical" Down syndrome, and doesn't correlate with the proportion of irregular cells detected in lymphocytes or fibroblasts. Nonetheless, on typical, psychological retardation in mosaic trisomy 21 is generally milder than in nonmosaic trisomy 21.

Who Has Down Syndrome Babies? by: Jane Orville

Most people associate having a child with Down syndrome with older women. While it is true that women over 35 do have an increased risk of having a child with Down syndrome, 80% of these children are born to those women under age thirty-five.

In the United States, approximately 5,000 babies with Down syndrome are born every year. A woman’s chance of having another baby with Down syndrome is approximately 1 in 100.

Prenatal Screening for Down Syndrome

Over the last 10 years, new technology has improved the methods of detection of Down syndrome. While there are ways to diagnose Down syndrome by obtaining fetal tissue samples by amniocentesis or chorionic villus sampling, it would not be appropriate to examine every pregnancy this way. Besides greatly increasing the cost of medical care, these methods do carry a slight amount of risk to the fetus.

So screening tests have been developed to try to identify those pregnancies at "high risk." These pregnancies are then candidates for further diagnostic testing.

Screening Vs Diagnostic Test

What is the difference between a screening test and a diagnostic test? In diagnostic tests, a positive result very likely means the patient has the disease or condition of concern. In screening tests, the goal is to estimate the risk of the patient having the disease or condition.

Diagnostic tests tend to be more expensive and require an elaborate procedure; screening tests are quick and easy to do. However, screening tests have more chances of being wrong: there are "false-positives" (test states the patient has the condition when the patient really doesn't) and "false-negatives" (patient has the condition but the test states he/she doesn't).

Maternal Serum Screening

The mother's blood is checked for three items: alpha-fetoprotein (AFP), unconjugated estriol (uE3) and human chorionic gonadotropin (hCG). These three are independent measurements, and when taken along with the maternal age (discussed below), can calculate the risk of having a baby with Down syndrome.

A very important consideration in the screening test is the age of the fetus (gestational age). The correct analysis of the different components depends on knowing the gestational age precisely. The best way to determine that is by ultrasound.

Test results are sometimes reported to doctors as "Multiples of the Median (MoM)." The "average" value is therefore called 1.0 MoM. Down syndrome pregnancies have lower levels of AFP and estriol, so their levels would be less than 1.0 MOM.

hCG in a Down syndrome pregnancy would be greater than 1.0 MoM.

Finally, the calculated risk is used to modify the risk already statistically calculated based on the mother's age. We already know that as the mother's age advances, the risk of having a baby with Down syndrome increases.

For example: Let's say the test results come back in the typical range for a pregnancy not associated with Down syndrome (that would be 1.0 MoM for all components). This result reduces the woman's risk of having a child with Down syndrome four-fold.