Causes and Types Of Edwards Syndrome in India: Trisomy 18 Treatment Options

Meaning

Edwards Syndrome is a genetic abnormality in which the baby has an extra copy of chromosome 18. It is named after a British Geneticist, John Edwards who first described this condition in 1960.

Development

There are twenty-three pairs of chromosomes in a healthy person. Chromosomes are thread-like structures present in cells that contain all the genetic information of the person.

A boy inherits an X chromosome from his mother and a Y chromosome from his father. But a girl inherits an X chromosome each from both her parents. This is how a healthy person gets twenty-three chromosome pairs, one of each pair from one parent (in total, forty-six chromosomes).

However, an Edwards’ syndrome baby has an incorrect number of chromosomes. It usually happens by chance due to an error in cell division during embryonic development.

The mother’s egg and father’s sperm fuse together to form an embryo with the combined chromosomes. When either the sperm or the egg possesses an incorrect number of chromosomes, the abnormality can pass onto the embryo, resulting in trisomy.

The child inherits an extra chromosome from a parent in chromosome 18, either whole or in part, making it a set of three chromosomes instead of a pair. Hence, it is also given the name “Trisomy 18”.

It is also called “chromosome 18 duplication”, “Edwards’ syndrome 18” or “trisomy E syndrome”.

Frequency

This syndrome is the second most common trisomy after Down syndrome, which is caused by an extra chromosome 21.

Unfortunately, most fetuses with this condition don’t survive past the third trimester of pregnancy. Those who do survive are born with severe neurological and physical abnormalities and have just a few days or weeks to live. An Edward syndrome baby lives a year or sometimes a little more than that.

Edwards’ syndrome is a chromosomal abnormality that occurs before birth. The extra chromosome hampers the healthy development of the fetus resulting in fatal consequences for the child. This abnormal number of chromosomes is mostly the result of nondisjunction, an error during cell division which causes the baby’s organs to develop abnormally.

Causes and Risk Factors

There is no known, definite cause of Edwards syndrome. However, many studies over the years have emphasised on certain risk factors that may increase your chances.

Types of Edwards Syndrome

1. Full

It is also known as primary trisomy. Most cases of trisomy 18 come under this type. In this, the third copy of chromosome 18 exists in all of the cells. he Edwards’ syndrome effects of this type are often severe, and most babies are stillborn. Profound intellectual disability is common in full trisomy 18.

Inheritance Pattern: Full Edwards’ syndrome is not an inherited condition as it occurs during egg or sperm formation in the parents.

2. Mosaic 

It is a rare type of trisomy 18 in which the third copy of chromosome 18 exists in some of the cells. Approximately 5% of all cases of trisomy 18 are of this type. The severity of symptoms in mosaic trisomy 18 depends on the type and number of cells that have the extra chromosome.

Inheritance Pattern: This type is also not an inherited condition. It occurs randomly.

3. Partial 

In a partial Edwards syndrome, a section of the long arm of chromosome 18 attaches itself to another chromosome at the time of embryo development. It is also known as chromosome translocation as it is caused by unbalanced translocation of chromosomes.

In such a case, doctors often advise parents to undergo chromosomal analysis as it can affect future pregnancies as well. The physical symptoms in it may be less severe than other types of trisomy 18. It affects less than 1% of all cases.

Inheritance Pattern: Partial Edwards’ syndrome can be inherited since an unaffected person can carry such a genetic rearrangement, which increases their risk of having children with this syndrome.

However, it is significant to note that Edwards’ syndrome isn’t always inherited. In fact, most of the cases occur randomly during cell division, right in the early stages of fetal development.

Edwards’ syndrome symptoms are classified as:

Physical Symptoms

There are a number of physical symptoms of Trisomy 18:

Other symptoms also include:

Skull and Facial Abnormalities:

• Low-set and deformed ears
• Small facial features, especially the jaw
• The head is significantly smaller – microcephaly
• A cleft lip
• Feeding problems
• Ear infections
• A hole or defect in the iris – coloboma of the iris

Skeletal Abnormalities:

• A deformed thumb
• Clenched hands with overlapping fingers
• A short breastbone
• Underdeveloped nails
• Crossed legs
• Rocker-bottom feet

Other Organ Abnormalities:

• Breathing difficulties, along with other lung issues like pneumonia.
• Gastrointestinal abnormalities like defects in the abdominal wall, umbilical hernia, etc.
• Kidney disorders like excessive fluid retention, cysts, horseshoe kidneys, etc.

Neurological Symptoms

Other than physical disorders, this chromosomal condition causes many neurological defects in the baby as well, including:

• Fluid build-up in the brain
• Decreased range of motion
• Underdeveloped brain
• Seizures

All these symptoms, along with other brain malformations, consequently cause severe learning disability and developmental disorders in children with Trisomy 18.

This syndrome’s cognitive symptoms and physical disabilities cause life-threatening disorders that often prove fatal. Though it affects different babies differently, it has the potential to impact the whole body severely. Such babies require specialised care in hospitals or nursing homes.

A Case Study

Let’s look at an Edwards’ syndrome baby case from India published in E-Cronicon, which will help you understand the symptoms better.

Key Findings of the Case Study

The case is about a six-year-old old female child from India who came with weight gain issues and deformed limbs. She was born at 8 months of her mother’s pregnancy at home, weighing a bare 1.5 kg. At the time of her birth, the father and mother were 31 and 28 years old respectively.

A physical examination, along with various diagnostic tests, was performed to ascertain the cause of the condition. The findings of the case included:

• Triangular face with a prominent back portion of the head
• Low set ears, upturned nose, large space between eyes with an abnormally small jaw structure
• Underdeveloped nails with reduced range of motion in fingers
• Deformities were seen in the central nervous system
• Soft audible murmur was heard in the chest area
• Problems with mental and motor development were also observed

Apart from the above conditions, no other abnormality was detected in the diagnostic tests. Function tests of the liver, kidneys, and thyroid were normal. The abdominal ultrasound and X-Ray of the vertebral column also showed normal reports.

On chromosome analysis, 47 chromosomes were found with an extra copy on chromosome 18, revealing in an Edwards’ syndrome baby

Most of this condition’s diagnoses happen prenatally, at present. Laboratory testing for trisomy 18 in India includes Edwards’ syndrome karyotype test, fluorescent in situ hybridization (FISH), quantitative PCR, multiplex ligation probe amplification (MLPA), chromosomal microarray (CMA).
These tests can distinguish full trisomy 18 from mosaic or partial trisomy 18. While the FISH test can determine trisomy 18 with a rapid turnover time, the CMA test is comparatively more expensive and takes longer.

Let’s discuss the various tests that doctors conduct during and after pregnancy to diagnose the syndrome.

Initial Screening

Combined Test

A screening test is available for pregnant women between 10 and 14 weeks of pregnancy. It is known as a combined test because it combines an ultrasound scan with a blood test for a proper diagnosis.

This scan determines “nuchal translucency” by measuring the fluid at the back of the baby’s neck. The doctor checks your age and the test results to assess the chances of the baby having Edwards’ syndrome.

However, obtaining a nuchal translucency measurement depends on the baby’s position in the uterus and may not always be possible.

Mid-Pregnancy Scan

If the mother is too far into the pregnancy, the doctor may offer to do a mid-pregnancy scan. It is a test done at 20 weeks of pregnancy. Its main motive is to test for Edwards’ syndrome symptoms in the baby that point towards the physical disorder.

One or more of these abnormalities are observed in the ultrasound findings in 90 per cent of the cases:

• Restricted growth
• Strawberry-shaped skull
• Polyhydramnios – excess amniotic fluid in the amniotic sac
• Choroid plexus cyst – a small fluid-filled space that occurs in the brain
• Congenital heart defects
• Overlapping fingers of the hands – 2nd on 3rd and 5th on 4th
• Single umbilical artery
• Omphalocele – abdominal wall defect

However, it isn’t the most accurate method to assess the condition. Other more precise prenatal methods directly take the cells and screen the chromosomes. These methods include:

Diagnostic Tests During Pregnancy

Amniocentesis

It is a prenatal procedure performed between 16 and 20 weeks into the pregnancy. In this, the doctor takes a sample of amniotic fluid which contains the fetal cells for testing. This is a clear, pale yellow fluid that surrounds the fetus in pregnant women.

The doctor analyses the chromosomes present in the fetal cells for signs of trisomy 18 or any other possible abnormality. The same test is also useful in evaluating other genetic conditions like Down’s syndrome and Patau’s syndrome.

Chorionic Villus Sampling (CVS)

Also called chorionic villus biopsy, CVS involves taking a tissue sample from the placenta. The chorionic villi of the placental tissue contain the genetic material of the fetus which the doctors use to analyse the chromosomal abnormalities in the developing baby.

This test typically takes place between the 10th and 12th weeks of pregnancy. The doctor either takes the tissue sample through the cervix or a needle inserted into the abdomen.
However, both amniocentesis and CVS are invasive procedures and carry a small risk of miscarriage. It is wise to get all information from the doctor before going ahead with any test.

Diagnostic Test After Pregnancy

After the birth of the baby, the doctor can check for the syndrome through physical examination for prominent facial and bodily symptoms. Additionally, the doctor will also conduct a blood test for more accurate results as it is a better way to detect a chromosomal defect. After conducting the tests, the doctor will discuss the test results and provide suitable suggestions.

COVID-19 outbreak and infants

The second wave of COVID-19 outbreak in India has not spared even newborn children. If the mother had tested positive for novel coronavirus during pregnancy, reports suggest that there could be dangers of preterm labour. Additionally, at the time of delivery, there are high chances that the baby is infected with coronavirus as well. Doctors will conduct a COVID test on the baby and if it is positive, the baby might be separated from the mother and given treatment in the Neonatal Intensive Care Unit.

The diagnosis can be emotionally overwhelming for the parents. Experts recommend a balanced approach while counselling such parents. Information regarding survival rate, recurrence risk, treatment options, needs to be shared with absolute empathy and compassion.

It is, no doubt, difficult for parents to have a child diagnosed with Edwards syndrome. Seeking support from different sources plays a vital role in their emotional well-being. In cases of prenatal diagnosis, the doctor may even suggest ending the pregnancy as there’s no known cure or permanent treatment.

Edwards’ Syndrome Prognosis

Treatment

After careful prenatal diagnosis, if the parents decide to continue the pregnancy, they’re made aware of the medical complications of having a baby with trisomy 18. In fact, several health professionals can assist you in dealing with this condition to help in improving the quality of life.

Let’s learn about some measures that the doctors often adopt in such cases:

• Managing the Edwards’ Syndrome Symptoms:

After the diagnosis, the primary focus of the doctors is to do their best to reduce the occurrence of its debilitating symptoms. Due to their severe nature, parents probably need help from different health specialists to care for the child.

Managing Edwards’ syndrome symptoms can be a challenging task in itself. The doctors provide symptomatic treatment depending on the areas of the body where the child is facing abnormality.

For instance, if your baby has feeding problems, the doctors will need to use a feeding tube. Oxygen is arranged as necessary for children with respiratory issues. Surgical solutions are available for cardiac defects if parents are comfortable with this route.

• Supportive Treatment:

The child may also require supportive treatment like physiotherapy and occupational therapy. Problems with the neurological system and muscle tone severely affect the child’s motor skills. The doctors suggest supportive-treatment to improve their daily life.

While physiotherapy helps with the movement and function of the body, occupational therapy helps in improving the ability to do everyday tasks.

• Carer Support for the Child:

A baby born with this syndrome will have many physical abnormalities that require constant care from a committed primary care practitioner as doctors and parents work together to treat various medical issues.

Preparation and emotional support are also vital for the carers and providers of the baby. They also need to keep fit and healthy and keep taking short breaks in between for their overall well-being.

However, despite a dim prognosis, the world has seen a few miraculous examples where an Edwards’ syndrome baby has lived a healthy life.

– Dr. Pragnya Rao, General Physician

Doctors recommend guidance and counselling for families coping with this condition. The most significant part of joining a support group is not losing hope and faith in what is to come.

Families can seek help from appropriate support groups. These support groups have played a significant role in extending help and understanding to families going through this syndrome. Also, there are several charity organizations set up who offer financial aid to parents during this difficult time.

Q1. How often does Edwards syndrome occur?

Edwards syndrome or Trisomy 18 is a rare condition affecting one in six thousand live-births. However, in about one in four hundred pregnancies, Trisomy 18 is diagnosed, but most of the babies die before birth or are still-born.

Q2. What is the life expectancy for Edwards’ syndrome diagnosed babies?

The average life expectancy for Edwards’ syndrome baby is three days to two weeks. About 1 percent of children live beyond their first birthday.

Q3. What is the primary risk factor for developing Edwards’ syndrome?

The most critical risk factor is an older mother. The risk increases with advancing maternal age, especially after 32 years.

Q4. Can Trisomy 18 be prevented?

Since most of the cases happen randomly due to an error with cell division during early fetal development, one cannot prevent Edwards’ syndrome.

Q5. How is Edwards’ syndrome or Trisomy 18 inherited?

Edwards’ syndrome is mostly not inherited. Only in cases of partial syndrome which in itself is very rare, the condition may pass on to the child from parents.

Q6. How does Trisomy 18 cause developmental delays?

All babies born with Trisomy 18 have some sort of learning disability due to an underdeveloped brain along with various other mental and physical disorders. It results in severe developmental delays in babies.

Q7. How common are congenital heart defects in an Edwards syndrome baby?

More than 90 percent of cases are born with congenital heart defects. Cardiac failure is the leading cause of sudden death in children born with this syndrome.

Q8. Are there any risks associated with amniocentesis and CVS procedures?

Both amniocentesis and chorionic virus sampling are invasive procedures that carry a slight risk of miscarriage and injury to the developing baby.

Q9. Which is the most accurate way to diagnose Edwards syndrome after pregnancy?

A blood test is the most precise way to diagnose this condition after pregnancy. The Edwards’ syndrome karyotype can directly be determined and analyzed.

Q10. Can Edwards’ syndrome be cured?

Unfortunately, there is no known, permanent cure. Even managing the symptoms can be quite challenging for the parents. Several health specialists are needed to assist in such conditions.

Q11. Can you have a healthy pregnancy after Edwards syndrome?

The recurrence risk for Edwards’ syndrome is one per cent. So, yes, one can easily have a normal delivery after having a baby with Edwards’ syndrome.

Bottom line:

Raising awareness about Edwards’ syndrome or trisomy 18 will go a long way in helping families prepare and know about the challenges that come with each trisomy. Most importantly, just the feeling of knowing that they’re not alone in this fight will lift their spirits and give them hope, which is the least one can do for such families.