What Causes Edwards Syndrome: Trisomy 18, a Rare Genetic Disorder

DNA double helix structure
"By: Darwin Laganzon/Pixabay"

What is Edwards Syndrome (Trisomy 18)?

Edwards Syndrome, also known commonly as Trisomy 18, got its name from John Hilton Edwards, the British Geneticist, who first identified this genetic condition.

Edwards et al. reported the syndrome in a neonate that had many congenital disorders in 1960, but the confirmation of the involvement of chromosome 18 in Edwards Syndrome was given by Smith et al. Hence what causes Edwards Syndrome is majorly an extra chromosome in the cells of the affected individual.

Trisomy 18 is an autosomal condition which happens due to an extra copy of chromosome 18. Though rare, this genetic condition can be very serious, as currently there is no known cure for it. There are various other names for this condition, like Trisomy E Syndrome and Complete Trisomy 18 Syndrome.

Every 1 out of 3600 to 10,000 babies born have Edwards syndrome, but this live birth frequency can vary across different countries, mainly due to differences in their pregnancy termination policies. As the average maternal age has increased in the past years, the frequency of Edwards Syndrome has also increased. With the increase in the mother’s age, the chances of having a baby carrying this condition also increases.

As there are severe as well as multiple life-threatening birth defects associated with Edwards Syndrome (trisomy 18), most babies die during birth or do not survive past their first month.

Causes of Edwards Syndrome

Trisomy 18 occurs due to a genetic defect in either the egg or sperm cell that were involved in fertilization. A human somatic cell is normally diploid, that means it contains two copies of a chromosome, one from the mother or the egg cell and one from the father or the sperm cell. In case of Edwards Syndrome, cells affected contain an additional chromosome 18. The abnormal amount of genetic content interferes with the normal development of the baby.

During any one of the two meiotic cell division, the chromosome can fail to segregate, and this can lead to an extra copy of the chromosome in the daughter cells formed. This daughter cell can be a sperm cell or an egg cell.

This failure of chromosome to segregate during cell division is called nondisjunction, and in Edwards Syndrome, this cell division error occurs during meiosis, either in meiosis I or meiosis II, but most frequently occur during meiosis II.

What causes Edwards Syndrome : Fertilization of a gamete having an extra chromosome with a normal gamete
“By: Mohamed Hassan/Pixabay

Hence the affected gamete will have 24 chromosomes while the other gamete will have 23. On fertilization, the resulting zygote will contain 47 chromosomes, with three copies of chromosome 18 or trisomy 18. This extra chromosome is more likely to come from the mother’s side.

A chromosome usually contains two arms, divided by the centromere. Edwards syndrome phenotype is reported to possibly be due to the three copies of two important locations on the chromosome’s long arm. One of these region is linked to severe intellectual disabilities.

Types of Edwards Syndrome

Edwards Syndrome is of three types.Trisomy 18 is mostly not inherited and occurs randomly because of an error in segregation during meiotic cell division in gametes. Full Edwards Syndrome as well as Mosaic Edwards Syndrome are not inherited whereas Partial Edwards Syndrome is inheritable.

1. Full Trisomy 18 or Full Edwards Syndrome

It is the most severe type amongst the three, as every cell of the body is affected, and contain an extra chromosome or trisomy 18. Hence there are 47 chromosomes in all of the body’s cells.

Most babies with Full trisomy 18 die before they are born. Other than being the most severe, it is also the most frequently occurring trisomy 18 and occurs in about 94% of the cases with Edwards Syndrome.

2. Mosaic Trisomy 18

This condition is comparatively less severe. This creates a mixed cell population, where some of the cells contain two chromosomes while some contain three.

It occurs in less than 5% of the babies having trisomy 18. Most babies born with Mosaic trisomy 18 can live up to minimum of one year and can grow well into their adulthood.

The severity of this type is dependent on what type of cells and how many cells contain trisomy 18. Thus the phenotype of the babies with this type can have a range from normal development to severely affected which may be along with early mortality.

3. Partial Trisomy 18

Partial trisomy 18 occurs in the least frequency amongst the three types, in less than 2%. In the cells affected, instead of an entire extra chromosome, only a section is present. Hence in this type, the child may be less severely affected. What causes Edwards syndrome partial trisomy 18 is a chromosomal translocation event.

Due to translocation, a part of the chromosome 18 gets attached with another chromosome, hence the affected individual has two copies of chromosome 18 and an extra part of chromosome 18. This can occur during the formation of either of the gametes or during an early stage of embryonic development.

Here the translocation is of the long arm of the chromosome, where a part or the entire arm of chromosome 18 can get attached to another chromosome. If in an affected individual, only a part of that chromosome arm is present, then the phenotype is less severe than that of full Edwards Syndrome. If the affected individual has the entire long arm of the chromosome 18, then the phenotype is more severe, and is similar to full Edwards Syndrome.

This is an inheritable type of trisomy 18, as here a balanced translocation occurs. A balanced translocation is when a section on a chromosome gets evenly exchange with another chromosome, but the genetic material remains the same, not more nor less. People having this balanced translocation have a higher probability to have a baby with trisomy 18.

Common Symptoms of Edwards Syndrome

The symptoms can be observed during pregnancy as well as after birth.

Symptoms During Pregnancy

A prenatal diagnosis like ultrasound can be done to check for symptoms of trisomy 18, and can further be verified using chorionic villus sampling and amniocentesis. Trisomy 18 can cause many birth defects.

  1. umbilical cord containing only one artery
  2. small sized placenta
  3. higher volume of amniotic fluid around fetus
  4. low level of fetal movement
  5. choroid plexus cysts

Symptoms After Birth

More than one congenital anomalies and birth defects can be caused due to trisomy 18, and are usually severe in nature.

  1. low set ears
  2. small head and jaw size
  3. severe intellectual disabilities
  4. heart defects like atrial septal defect, ventricular septal defect etc.
  5. cleft lip
  6. overlapping fingers over a clenched fist
  7. weak cry
  8. low birth weight
  9. joint contractures
  10. kidney defects
  11. seizures
  12. apnea

What Happens to Babies Born with Edwards Syndrome?

About 40% of the fetuses with Edwards Syndrome sadly die during labor. Out of all the fetuses that survive, around one-thirds of them have a preterm delivery. The median survival time for the babies lies between from 3 to 14 and a half days. Sadly, only about 5 to 10% of the babies survive past their first birthday.

Female babies with Edwards syndrome have a higher survival probability than male babies. The leading cause of fatality in babies with Edwards Syndrome is cardiac or respiratory failure.

What are the Complications Involved with Edwards Syndrome

1. Delayed Growth

Babies with Edwards Syndrome have a low birth weight and delayed growth which can cause problems like feeding complications.

2. Developmental Delays

Motor disabilities, intellectual disabilities, delay in cognitive development, physical developmental complications etc. occur in children born with Edwards Syndrome.

3. Cardiac and Respiratory Defects

These defects are the major cause of fatality in babies with Edwards Syndrome. It can include hypoventilation, apnea, heart defects etc.

4. Arthrogryposis

It is a congenital muscle disorder, where the affected baby has joint contractures in more than one area of the body.

5. Omphalocele

A congenital defect where the abdominal wall of the baby is affected. The baby’s intestines or other organs of the abdomen are present outside the baby’s body in a transparent sac like structure.

6. Esophageal Atresia

It is a congenital defect that causes the baby’s esophagus to not develop in a proper manner. The upper part of the esophagus is not able to from proper connections with the esophagus’s lower region as well as the stomach.

How to Diagnose Edwards Syndrome During Pregnancy?

The diagnosis of Edwards syndrome (trisomy 18) can be done during pregnancy. What causes Edwards syndrome is  a genetic abnormality, and hence genetic testing can be done to check for its presence. Serum of the mother can be tested for the presence of certain markers that can indicate if the fetus has any genetic condition or not.

In the serum, a low level of the human chorionic gonadotropin, alpha fetoprotein etc. can all act as markers for Edwards syndrome. A diagnostic test is suggested when there is a high risk of a condition observed during screening tests.

1. Combined Screening Tests

It is a screening test that is used to screen for Down syndrome, Edwards syndrome and Patau syndrome during pregnancy, between week 10 and 14. As this test combines a nuchal translucency ultrasound with a blood test, hence it’s termed as combined test. If there is found a high risk after the screening tests, the patient is advised to undergo diagnostic tests.

2. Non Invasive Prenatal Testing

What causes Edwards syndrome is excess genetic material. So if we can check the fetus’s genetic material, we can find out if the fetus has Edwards Syndrome. This screening test requires only a blood sample from the mother. Plasma is isolated from the blood sample, and that plasma is used to obtain cell-free DNA (cfDNA), which are fragments of DNA that are freely circulating in the mother’s blood.

Fetal DNA is the same as the placenta DNA, and the cfDNA in the mother’s blood comes from both, her cells as well as the placenta. Hence the cfDNA coming from the placenta can be used to look for abnormalities in the fetus’s genetic material.

3. Chorionic Villus Sampling Diagnostic Test

Chorionic Villi are finger like structures present on the placenta. As the placenta contains the same genetic material like the fetus, the villi will also have the same genetic architecture as the fetus, hence the baby’s cells can be tested using this method. Using biopsy technique, a sample of placenta issue is collected and then analyzed for genetic disorders. It is done between week 11 and 14 of pregnancy.

3. Amniocentesis Diagnostic Test

Amniotic fluid helps in exchange of nutrients and other important products as well as provide safety to the growing fetus. It contains fetal cells and hence a sample of this amniotic fluid can be used to test for abnormal genetic conditions in the fetus.

How to Diagnose Babies Born with Edwards Syndrome?

1. Blood Test

A blood test of the baby suspected to have Edwards Syndrome can be done.

2. Physical Examination

A physical examination can be performed for any external birth defect.

3. Diagnostic Imaging

Imaging techniques like ultrasonography can be used toc check for birth defects like in brain, heart etc. The babies can have multiple congenital anomalies caused by trisomy 18, hence a screening may be required. Some of these techniques are

  1. Echocardiogram
  2. MRI
  3. Abdominal ultrasonography
  4. Renal ultrasonography

How to Treat Babies With Edwards Syndrome

There is no known cure for this genetic condition. But there are supportive and symptomatic treatments available. There is no rigid treatment method as it is personalized depending on the symptoms of the baby as well as the parent’s choices.

1. Neonatal Intensive Care Unit

NICU (Neonatal Intensive Care Unit) is a specially crafted unit for new born babies who are either premature borns or have certain health conditions.

2. Feeding Tube

Children with Edwards Syndrome may face difficulty in feeding due to delayed physical development. Assisted feeding methods like nasogastric tube and gastrostomy feeding tubes can be used.

3. Cardiac Treatment

Corrective cardiac surgery as well as palliative cardiac surgery can be done, but not all children will be eligible for the surgery. In case of heart failure, diuretics and digoxin can be employed.

4. Orthopedic Treatment

Bracing or a surgery can be used to treat problems like scoliosis.

The following video from NHS shows the stories of three families having a child with Edwards Syndrome.

Psychiatric Management for the Parents

Psychosocial support can be provided to the parents. They should be made aware about the resources and support organizations. Support is given to help the parents and the child to correctly manage and navigate the diagnosis. Support is also given to parents to deal with the loss of their child due to Edwards Syndrome.

Parents can also talk to other families who might have gone through the same circumstances. This can be done by contacting support groups, or using social media. Legal support as well as some financial aid is also available to individuals affected with an illness, with policies varying according to different countries.

If a fetus has been diagnosed with Edwards Syndrome, the parents can undergo prenatal counselling. As there is a high fatality rate associated with Edwards Syndrome, parents have to be made aware of all the statistics related to survivability and the post natal symptomatic treatment options available.

What causes Edwards Syndrome is a chromosomal segregation error occurring during any one of the meiosis stages, but can cause many devastating outcomes. It can lead to multiple birth defects in the baby and are usually fatal in nature. Cardiac and respiratory complications are the leading cause of fatality in Edwards syndrome. It is important that parents should be made aware of every aspect of this genetic condition to be able to navigate through the difficult disorder. They should be aware of the diagnostic and treatment methods available for both prenatal and postnatal periods.

Parents and their children affected with Edwards Syndrome (trisomy 18) should never be burdened with any guilt. Proper support should be given to the parents and they should be made aware of all the consequences of keeping or terminating the pregnancy.

Despite having very low survivability rates, one can make sure that the child remains as comfortable as possible. It is important the the child be treated with utmost respect and care. The child is his/her/their own own individual and should be respected as one.


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I am currently pursuing B. Tech in Biotechnology from Delhi Technological University, Delhi, India. My favorite subjects include Genetics, Genetic Engineering and Molecular Biology. I would one day like to go into the research field to study and find treatment for various disorders. I have written many review articles as a part of my college project related to different disorders, which help me to gain insight into the pathogenesis, diagnosis and treatments of many diseases.
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