THE CORRELATION BETWEEN MATERNAL AGE AND CHILDREN WITH DOWN SYNDROME

Written by: Vira Riezky Yanwika 03007265

FACULTY OF MEDICINE TRISAKTI UNIVERSITY JAKARTA 2010

ABSTRACT
The association between maternal age and risk of Down syndrome has been repeatedly shown in various populations. Increasing maternal age also increases the possibility of the development of chromosomal abnormality or genetic disease in a child. Down syndrome (also called trisomy 21 or trisomy of chromosome 21), is the most common chromosome abnormality in newborns. Although Down syndrome affects a relatively small number of families directly, internationally it is discussed with millions of parents every year when they are offered prenatal screening. Many studies have shown the correlation between the developments of chromosomal abnormality in a child is associated with the maternal pregnancy age. Keyword: Down syndrome, trisomy 21, chromosomal abnormality

INTRODUCTION
Womens fertility usually begins at the age 18 and reaches its peak at the age of 25, after which it gradually declines for the succeeding years until the age of 35, where the decline progresses rapidly. At 40, it is expected that women will have difficulty getting pregnant.
(1)

However, all these are just numbers. As soon as a woman starts menstruating and as long as

the woman has not reached the menopausal stage, getting pregnant is possible. But pregnancy age of 35 or more can be causes many risk. One of them is Down syndrome children. The possibility of having a Down syndrome child increases with the increasing maternal age. The risk is minimal that is 1 in every 1500 births when the maternal age is 20, as the age increases the risk also increases. When the maternal age is 35 the risk increases to 1 in every 50 births.
(1,2)

Chromosomes are structures which carry the genetic material or genome of a person. In human 23 pairs of chromosome are present in every cell of their body. One set inherited from the mom and the other from the dad. 22 pairs of chromosome are autosomal, that is these

chromosomes dictate the characteristics, behaviour of a person. The remaining one pair is the sex chromosomes; they determine the sex of a person. If both are X-chromosomes then the individual is female. If one is Y then the individual is male.
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(3)

Chromosomal abnormalities

some time are inherited from the parents, and also some random mutations may occur in the

unborn foetus or children without the family history of disease. The factors which can cause such abnormalities in the chromosome include age of the mother, exposure to the radiation during pregnancy and other environmental factors. (4) Down syndrome is a most common chromosomal abnormality which has got a strong link with the maternal age is Down syndrome. In Down syndrome, the baby has got three chromosome 21 instead of a pair.
(5)

That is all the genes present in chromosome 21 are

present in an extra copy in all Down syndrome patients. Meiotic recombination patterns change as a woman ages. However, this is almost certainly not the case: meiotic exchanges for oocytes are established during the fetal period, and there is little reason to think that a second round of recombination occurs in the adult ovary. Thus, the associations among age, recombination, and nondisjunction must be more complex. (4,5) Almost all cases involve errors in meiosis, the complex process in which one round of DNA replication is followed by two cellular divisions to generate haploid gametes. The first cell division (meiosis I) separates homologous chromosomes, the second (meiosis II) segregates the sister chromatids of each homologue. Nondisjunction can occur at either of these stages and can generally be distinguished with the use of polymorphic genetic markers at or near the centromere of the nondisjoined chromosomes . If both copies of the nondisjoined chromosomes are heterozygous for alleles at these markers, it is likely that the error arose at meiosis I. In contrast, homozygosity at the centromere suggests an error at meiosis II. (4,6)

Down syndrome, also called Trisomy 21, is a condition in which extra genetic material causes delays in the way a child develops, both mentally and physically. It affects about 1 in
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every 800 babies. The physical features and medical problems associated with Down syndrome can vary widely from child to child. While some kids with Down syndrome need a lot of medical attention, others lead healthy lives. Though Down syndrome can't be prevented, it can be detected before a child is born. The health problems that can go along with Down syndrome can be treated, and there are many resources within communities to help kids and their families who are living with the condition. (7) Normally, at the time of conception a baby inherits genetic information from its parents in the form of 46 chromosomes: 23 from the mother and 23 from the father. In most cases of Down syndrome, a child gets an extra chromosome 21 for a total of 47 chromosomes instead of 46. It is this extra genetic material that causes the physical features and developmental delays associated with Down syndrome. (8) In study, women age 35 and older have a significantly higher risk of having a child Down syndrome. At age 30, for example, a woman has about a 1 in 900 chance of conceiving a child with Down syndrome. Those odds increase to about 1 in 350 by age 35. By 40 the risk rises to about 1 in 100.
(8,9)

Down syndrome can result from several different genetic

mechanisms. This results in a wide variability in individual signs and symptoms due to complex gene and environment interactions. Prior to birth, it is not possible to predict the symptoms that an individual with Down syndrome will develop. Individuals with Down syndrome may have some or all of the following physical characteristics: flat back of head, microgenia (abnormally small chin), oblique eye fissures with epicanthic skin folds on the inner corner of the eyes (formerly known as a mongoloid fold), muscle hypotonia (poor muscle tone), a flat nasal bridge, a single palmar fold, a protruding tongue (due to small oral cavity, and an enlarged tongue near the tonsils) or macroglossia, a short neck, white spots on the iris known as Brushfield spots, excessive joint laxity including atlanto-axial instability, excessive space between large toe and second toe, simian line, single flexion furrow of the fifth finger, and a higher number of ulnar loop dermatoglyphs. Most individuals with Down syndrome have mental retardation in the mild (IQ 5070) to moderate (IQ 3550) range, with individuals having Mosaic Down syndrome typically 1030 points higher. They also may have a broad head and a very round face. The incidence of congenital heart disease in children with Down syndrome is up to 50%. A ventricular septal defect is the most common. (10,11.12)
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Language skills show a difference between understanding speech and expressing speech, and commonly individuals with Down syndrome have a speech delay. Fine motor skills are delayed and often lag behind gross motor skills and can interfere with cognitive development. Effects of the disorder on the development of gross motor skills are quite variable. Some children will begin walking at around 2 years of age, while others will not walk until age 4. Physical therapy, and/or participation in a program of adapted physical education (APE), may promote enhanced development of gross motor skills in Down syndrome children. Children may also have delayed mental and social development. Common problems may include impulsive behavior, poor judgment, short attention span, slow learning. Behavioral training can help people with Down syndrome and their families deal with the frustration, anger, and compulsive behavior that often occur. Parents and caregivers should learn to help a person with Down syndrome deal with frustration. At the same time, it is important to encourage independence. (13,14) Special education and training is offered in most communities for children with delays in mental development. Speech therapy may help improve language skills. Physical therapy may teach movement skills. Occupational therapy may help with feeding and performing tasks. Mental health care can help both parents and the child manage mood or behavior problems. Special educators are also often needed. Persons with Down syndrome are living
5

longer than ever before. Although many children have physical and mental limitations, they can live independent and productive lives well into adulthood. (15)

While some children with Down syndrome have no significant health problems, others may experience a host of medical issues that require extra care. All infants with Down syndrome should be evaluated by a pediatric cardiologist. Approximately half of all kids with Down syndrome also have problems with hearing and vision. Hearing loss can be related to fluid buildup in the inner ear or to structural problems of the ear itself. Vision problems commonly include amblyopia (lazy eye), near- or farsightedness, and an increased risk of cataracts. Regular evaluations by an audiologist and an ophthalmologist are necessary to detect and correct any problems before they affect language and learning skills. (16) Two types of prenatal tests are used to detect Down syndrome in a fetus: screening tests and diagnostic tests. Screening tests estimate the risk that a fetus has Down syndrome diagnostic tests can tell whether the fetus actually has the condition. Screening tests are cost-effective and easy to perform. But because they can not give a definitive answer as to whether a baby has Down syndrome, these tests are used to help parents decide whether to have more diagnostic tests. Diagnostic tests are about 99% accurate in detecting Down syndrome and other chromosomal abnormalities.
(17)

However, because they're performed inside the uterus,

they are associated with a risk of miscarriage and other complications. For this reason, invasive diagnostic testing previously was generally recommended only for women age 35 or older, those with a family history of genetic defects, or those who had an abnormal result on a screening test. However, the American College of Obstetrics and Gynecology (ACOG) now recommends that all pregnant women be offered screening with the option for invasive diagnostic testing for Down syndrome, regardless of age. Screening tests include Nuchal translucency testing, the triple screen or quadruple screen, integrated screen, a genetic ultrasound. And diagnostic test include chorionic villus sampling, amniocentesis. (18)

CONCLUSION
Maternal age is one of the factors contributing to the risk of having a child with chromosomal abnormality. At birth, women already have all the egg cells inside their body and as she ages, so do the eggs. The genetic materials of the eggs also change over time. Because of these changes, the chances of having a child with genetic problems increases as women also advance in age. In study, women age 35 and older have a significantly higher risk of having a child with the Down syndrome. Down syndrome is a most common chromosomal abnormality which has got a strong link with the maternal age is Down syndrome. In Down syndrome, the baby has got three chromosome 21 instead of a pair. That is all the genes present in chromosome 21 are present in an extra copy in all Down syndrome patients. Meiotic recombination patterns change as a woman ages. However, this is almost certainly not the case: meiotic exchanges for oocytes are established during the fetal period, and there is little reason to think that a second round of recombination occurs in the adult ovary. Thus, the associations among age, recombination, and nondisjunction must be more complex.
7

Almost all cases involve errors in meiosis, the complex process in which one round of DNA replication is followed by two cellular divisions to generate haploid gametes. The first cell division (meiosis I) separates homologous chromosomes, the second (meiosis II) segregates the sister chromatids of each homologue. Nondisjunction can occur at either of these stages and can generally be distinguished with the use of polymorphic genetic markers at or near the centromere of the nondisjoined chromosomes and causes Down syndrome.

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