“Trisomy 18 also known as the Edwards syndrome occurs due to the numerical chromosomal abnormality in which an extra copy of chromosome 18 present with a pair.”


 Trisomies are one of the common types of numerical chromosomal abnormalities reported in which trisomy 21, trisomy 18 and trisomy 13 are more prevalent. 

It is a common type of genetic abnormality occurs due to unknown reasons or unbalanced chromosomal distribution, unlike other inherited DNA mutations, the trisomy can not be inherited from their parents. 

Genetic abnormalities can be categorised broadly in two categories: gene mutations and chromosomal alterations. 

The chromosomal alterations are originated because of the alteration or mutations in chromosomes, numerical chromosomal abnormalities and structural chromosomal abnormalities are among it. 

The chromosomes are the inheritance unit of living organism on which the genes are located. In humans, 23 pairs of a chromosome are present, each chromosome are present in a pair in every cell, except the germ cells.  

The paired chromosomes are called a diploid number of chromosomes (2n), thus total 46 chromosomes are present in a cell. 

In numerical chromosomal alteration, these numbers are changed called aneuploidy. The trisomy is a type of aneuploid in which the chromosome number increase to 1 (46 +1=47). Change in a number of chromosomes can cause serious health problem  

During the process of meiosis of germ cells, the event called non-disjunction results in uneven distribution of chromosomes causes trisomy. 

In the present article, we will talk about one of the common types of trisomy known as Edward syndrome- the trisomy 18. 

The content of the article is: 

What is trisomy 18? 

A trisomy 18,  also known as Edwards’ syndrome is a rare form of the chromosomal aberration and a type of congenital genetic abnormality causes serious health problems. 

In 1960, John Hilton Edwards first reported it and hence from his name it is also known as Edwards’ syndrome.

1 in ~7000 newborns suffers from the trisomy 18 worldwide. Sadly, babies with Edwards’ syndrome die before or immediately after birth.   

It is the second most common type of autosomal trisomy after the down syndrome.


Autosomal trisomy– trisomy occurs in an autosomal chromosome is known as autosomal trisomy.

Among the 23 pairs of chromosomes, 22 pairs are autosomal chromosomes while a pair of sex chromosome decides the sex of a fetus; XX in female and XY in male called sex chromosomes.


Cytologically the condition of trisomy 18 is known as 47 XX/XY, +18

Although the severity of the disease depends on the type of trisomy 18 and based on that the baby may die before, early or late in adulthood. Three types of trisomy 18 are:

Complete trisomy 18: 

The entire or complete chromosome 18 occurs with the pair of chromosome 18. Thus three different 18 number of chromosome present in a cell and in all cells. 

Complete trisomy 18 is a serious congenital condition, the baby may die during the pregnancy in most cases or immediately after birth. 

Majorities of Edward syndrome are complete trisomy 18.

Partial trisomy 18: 

Instead of the entire chromosome 18, some portion of the chromosome 18 present in a cell with a pair. Furthermore, which part of the chromosome 18 partially present with the pair is still unknown for scientists. 

However, the severity of the disease depends on which extra part of chromosome 18 present in a baby. As per recent research, it is possible that the partial trisomy 18 occurs if one of the parents have abnormal chromosome 18. 

The babies with partial trisomy 18 may live for some time or up to adulthood with complex physical and mental problems. 

Mosaic trisomy 18: 

In the mosaic situation, two different types of cell populations occur in an individual; one with three 18 number of chromosomes and one with a normal pair of 18 number chromosome.  

Henceforth, the severity of the disease depends on the number of cells with trisomy 18. 

Mildly affected babies have less number of affected cells. 10% of babies with trisomy 18 have mosaic trisomy and live up to adulthood. 

Cause of trisomy 18:

An extra chromosome causes serious physical and mental problems. 

A non-inherited form of the genetic condition- trisomy 18 occurs due to the event called non-disjunction. 

As we said above, all the bodily cells have 46 chromosomes, except the germ cells. It contains only haploid set chromosomes; 23 in the sperm and 23 in the egg inherited 46 chromosomes to the fetus.

During the process of germ cell division- meiosis 1 or meiosis 2 uneven distribution of chromosome (known as nondisjunction) causes the abnormal distribution of chromosomes. 

During the second round of meiosis (in most cases) of one of the germ cell causes trisomy. It is believed that the origin of the trisomy is maternal with more than 90% cases of complete trisomy. 

Trisomy 18 is caused by nondisjunction process of uneven chromosomal distribution. 

Definition of Trisomy 18:

“Trisomy 18 is a type of chromosomal aberration in which an extra copy of chromosome 18 occurs with a pair through the process of non-disjunction.”

Symptoms of trisomy 18: 

Wide range on mental as well as physical symptoms is shown in the trisomy 18. Some of the common symptoms are: 

  • Low birthweight 
  • Comparatively small jaw and mouth 
  • Abnormal and smaller head 
  • Low-set ear
  • Cleft palate 
  • Underdeveloped small thumbs and fingers with clenched feet 
  • Breathing problem 
  • Heart, kidney and problems with other organs as well 
  • Urinary and ling infection (frequent)
  • Learning and mental disabilities 
  • Curved spine 
  • Small body 
  • Intellectual and mental disabilities 

Note: near to 100K cases of trisomy are reported in India.

Pictures of trisomy 18:

The picture of a baby with trisomy 18; (A) abnormal fingers, (B) clenched feet (C) underdeveloped hands and fingers.

Some of the common physical characteristics of the present condition are cognitive and psychomotor disability, growth deficiency, craniofacial feature, overriding figures and distinctive hand posture, nail hypoplasia, short sternum and hallux.

Newly born baby having trisomy 18 with cleft pellets.

Pregnancies with the trisomy 18 are at high risk of stillbirth, fetal loss and fetal death.

Diagnosis of trisomy 18: 

Ultrasound and karyotyping- a type of genetic test are commonly used as a diagnostic tool for screening the trisomy 18 in which the karyotyping is employed to validate the results on ultrasound. 

In addition to this, a new age genetic test is also now utilised for screening of present condition which we will discuss it in this part later. 

Ultrasound: 

The ultrasound method is used as a primary screening method for any type of trisomy the indications of it, later authenticated using the genetic testing. 

During 10 to 14 week of pregnancy, the ultrasound can be used for primary screening. 

If any risk can be detected associated with the pregnancy, immediately the pregnant women refer to genetic testing. 

 Karyotyping: 

Often known as chromosomal analysis, a type of genetic testing method different from the gene testing. 

Here first, amniotic fluid (amniocentesis) or chorionic villi sample is taken from the fetus and send to the genetic laboratory. 

The genetic professional grows the metaphase cells to obtain metaphase chromosomes and then perform karyotyping to find our genetic aberrations associated with chromosomes. 

Using the G banding or Giemsa banding technique chromosomal aberrations can be encountered if any.

A karyogram is prepared using the help of the computer software which helps in finding numerical or structural chromosomal anomalies associated with it. 

A typical karyogram of a patient with trisomy 18 performed using the G-banding.

Besides trisomy 18 other trisomies like trisomy 21 or trisomy 13 can also be encountered using the method. 

Although the method is painful- invasive and the chance or risk of pregnancy loss is higher in it.

Read our article on Karyotyping: A Karyotyping Protocol For Peripheral Blood Lymphocyte Culture

Non-invasive prenatal diagnosis: 

Nowadays scientists are using the non-invasive method to screen the trisomy 18 known as NIPD, often known as cell-free fetal DNA testing

During the pregnancy, some amount of fetal DNA is also circulating in the mother’s blood, called cell-free DNA. 

From the mother’s blood, fetal DNA is isolated and using which a genetic test is performed to encounter the trisomy 18. Generally, quantitative PCR employed to do so. 

The fetal DNAs are very less present in maternal blood thus sometimes it can not give results though, it is non-invasive.

Henceforth, unlike conventional karyotyping, it can not practise frequently. More research, protocols and validation are required to use it in routine diagnostics. 

Later during the pregnancy at 21-week congenital abnormality scanning test can be done for confirming results. 

Life expectancy: 

The average life span of the babies with trisomy 18 or complete trisomy 18 is 2 days to 2 weeks. Most babies die in the womb or immediately after birth. 

Babies with mosaic or partial trisomy can live up to adulthood though. Up to 80% of babies with Edwards’ syndrome die within 21 hours.

5-10% of babies with trisomy 18 may survive beyond the age of 1 year. 

Interestingly, approximately 80% of cases of trisomy 18 are in female, we can say pregnancy with a female fetus is at more risk of trisomy 18.  

The prevalence of Edward syndrome is high in the female babies, however, the rate of fetal mortality is higher in a male fetus. 

Suggestions for parents for making a decision: 

 No one can force anyone for aborting their child, it is parents own decision, especially, its mother’s decision. Many social and emotional issues are associated with it, therefore, we can advise a couple what to do next if the pregnancy is diagnosed with trisomy 18 positive. 

First of all, don’t be panic or emotional, immediately contact your doctor first.  

Stay calm and explain the situation to your doctor and understand what they are saying to you. 

There is very less chance that a baby with complete trisomy 18 will survive even after birth. 

even if it may, parents have to suffer emotionally, economically and socially; no one wants to see their child suffering from pain. 

So if your doctor or genetic counsellor advice for abortion; calmly think on it. 

It is a non-inherited condition and totally random, until and unless one of you have any chromosomal abnormalities associated with chromosome 18.  

None of you (not you or hour husband) is responsible for it, so do not blame each other for that and understand the situation. 

Even if one of you do not want to abort it, respect each other’s decision and go ahead. 

Remember, the chance of occurrence of the trisomy 18 increases as the maternal age increases. Females over 30 are comparatively at high risk of trisomy 18. 

Conclusion:

No such treatments are available for trisomy 18 thus prenatal screening programs are must required to prevent genetic abnormalities like trisomy 18. The trisomy 18 does not follow any specific inheritance pattern, so the chance of inheritance of it in next pregnancy is negligible.

Resources: 

Cereda A, Carey JC. The trisomy 18 syndrome. Orphanet J Rare Dis. 2012;7:81. Published 2012 Oct 23.