Edwards Syndrome (Trisomy 18)

What is Edwards Syndrome (Trisomy 18)?

Edwards syndrome, also known as trisomy 18 syndrome, is a genetic condition that happens due to an extra copy of the 18th chromosome in a person’s cells. It’s called an “autosomal chromosomal disorder” because it affects the autosomes, which are the chromosomes that don’t determine a person’s sex. Edwards syndrome is the second most common condition of this type, after trisomy 21, which is more commonly known as Down syndrome.

The condition was first identified by a team of researchers led by Edwards in 1960. They found it in a newborn child who had many birth defects and problems with brain development. Later, other scientists named Smith and their team confirmed that the extra 18th chromosome is what causes Edwards syndrome.

What Causes Edwards Syndrome (Trisomy 18)?

Edwards syndrome, a genetic disorder, typically happens when there’s an extra copy of a part of chromosome 18. This condition comes in three types: Complete, partial, and mosaic Edwards syndrome.

The most common type is complete Edwards syndrome. In this case, all the cells in the body have three full copies of chromosome 18, instead of the usual two. This usually happens when the chromosome doesn’t split correctly during cell division, particularly during the production of eggs or sperm. The extra chromosome usually comes from the mother. The likelihood of this defect happening increases as the mother gets older.

The second most common type, found in less than 5% of cases, is mosaic Edwards syndrome. This means that some cells have an extra copy of chromosome 18 while others are normal. Depending on how many cells have the extra chromosome, people with mosaic Edwards syndrome can have a range of symptoms, from very severe to almost none.

The rarest type is partial Edwards syndrome, which only accounts for about 2% of all cases. With this type, only part of chromosome 18 is extra. This typically occurs when there’s an equal swap of chromosome pieces or a rearrangement of one of the parents’ chromosomes. The symptoms of partial Edwards syndrome can vary based on location and extent of the extra part of chromosome 18.

The chance of having a baby with Edwards syndrome increases as the mother gets older. The risk of having another child with complete Edwards syndrome in future pregnancies is around 0.5% to 1%. However, if one of the parents has an equal swap of chromosome pieces resulting in a rearrangement in the child, like in partial Edwards syndrome, the risk can go up to 20% in future pregnancies.

Risk Factors and Frequency for Edwards Syndrome (Trisomy 18)

Edwards syndrome, also known as trisomy 18, is a condition that happens at birth. The number of these cases varies from 1 in every 3600 to 1 in every 10,000 live births. In the past twenty years, we’ve seen more cases of trisomy 18 due to an increase in the average age of mothers. However, the number of cases in each country can differ because of varying termination policies.

In the United States, Edwards syndrome typically occurs in about 1 out of every 2500 births while the prevalence of live births is about 1 in 8600.
The syndrome is more common in baby girls than in baby boys, with a ratio of 3:2.
However, unborn baby boys have a higher rate of fetal loss compared to unborn baby girls.
Additionally, baby girls with Edwards Syndrome have been observed to have a better survival rate compared to baby boys.

Signs and Symptoms of Edwards Syndrome (Trisomy 18)

Edwards syndrome is a genetic disorder that can cause a wide range of health problems. There are over 125 different issues that are linked to Edwards syndrome, but none of them are exclusively associated with it.

Most cases of Edwards syndrome are identified before birth. This can happen through screening based on the mother’s age and other risk factors or through ultrasound findings in the second trimester. Some features that may suggest Edwards syndrome during pregnancy include restricted growth for the baby, excess amniotic fluid, an incomplete connection between the two sides of the brain, cysts in brain tissue, thickening at the base of the fetus’s neck, a clenched hand with overlapping fingers, heart defects, part of the intestine poking through a hole near the belly button, and a single blood vessel in the umbilical cord. Babies with Edwards syndrome are at high risk of dying before or shortly after birth.

After birth, Edwards syndrome has several key features, as listed below.

Neurologic: Decreased muscle tone at birth followed by increased muscle tone, breathing pauses, seizures, poor feeding, and delayed mental and physical development.
Craniofacial: Small head, narrowing across the temples, bulging at the back of the skull, triangular and asymmetric face with facial paralysis, small eyes, wide-set eyes, fold of skin on the inner corner of the eye, short eyelid openings, a gap in one of the structures of the eyes, cataract, clouding of the eye’s surface, underdeveloped ridge above the eyes, upward or downward slant to the opening between eyelids, and unusual pigmentation of the eyes.
Nose: Prominent bridge of the nose with underdeveloped root of the nose, turned-up nostrils, and narrowing or blockage of the nasal passages.
Oral cavity: Smaller-than-normal lower jaw, small mouth, narrow high-arched palate, cleft lip, and cleft palate. Ears: Underdeveloped ears, skin tags in front of the ears, low-set or backward-turned ears, and malformed ears.
Skeletal: Severe growth delay, short neck, short breastbone, wide chest with or without small, widely spaced nipples, incomplete bone formation in the collarbone, half-formed or fused bones in the spine, curvature of the spine, indent in the chest, narrow pelvis and limited hip movement, hip dislocation, joint contractures, clenched hands with overlapping fingers, bent fingers, webbing of the fingers, single crease in the palm, bent fifth fingers, underdevelopment of the radius or thumbs, and underdeveloped nails.
Foot problems: Rounded bottom of feet with a prominent heel, clubfoot, bent big toes.
Heart: Heart defects in 90% of patients with Edwards syndrome. These could be a hole in the wall between heart chambers, persisting connection between the aorta and the pulmonary artery, a combination of four heart defects known as tetralogy of Fallot, the aorta overriding the ventricles, narrowing of the aorta, or underdeveloped left side of the heart. More than one heart valve may be affected (most commonly the aorta and pulmonary valve).
Lungs: Underdeveloped lungs, floppy windpipe and voice box, obstructive and central apnea, and early-onset high blood pressure in the arteries to the lungs.
Gastrointestinal: Protrusion of the intestines through a hole near the navel, a blockage in the esophagus with a connection to the windpipe, narrowing of the exit of the stomach, a blockage in the small intestine, twisted intestine, presence of a small bulge in the small intestine, gap between the rectus abdominis muscles, and hernia in the navel.
Genitourinary: Undescended testes, incomplete formation of the urethra and penis, small penis, enlarged clitoris, underdeveloped major labia, abnormal ovaries, a divided uterus, fused kidneys, absent kidney, and kidney swelling.
Central nervous system (affects 30% of cases): Underdeveloped cerebellum, a hole in the skull with brain tissue protruding through, absence of the brain and cranial vault, an increase in fluid in the brain, an anomaly where the brain does not divide properly, a condition where the brain tissue extends into the spinal canal, or an underdeveloped structure that connects the two halves of the brain.

Testing for Edwards Syndrome (Trisomy 18)

Trisomy 18, also known as Edwards syndrome, is a condition diagnosed through evaluations that start before a baby is born. This testing process often starts with maternal blood tests. These tests look for levels of proteins like alpha-fetoprotein and hormones like human chorionic gonadotropin and unconjugated estriol. If these levels are low, it can hint at the presence of Edwards syndrome.

While these blood tests can provide valuable information, they become more reliable when combined with ultrasound examinations. In an ultrasound, increased thickness in the back of a baby’s neck could be a sign of this condition. Non-invasive prenatal testing (NIPT) is another method of diagnosing trisomy 18. This approach studies the baby’s DNA found in the mother’s blood. On its own, NIPT can be correct about 60.7% of the time in detecting Edwards syndrome, but when combined with ultrasound, its reliability increases to 100%.

If the prenatal screening suggests a high risk, other tests like amniocentesis or chorionic villus sampling, which involve extracting fluid or tissue from the womb, are recommended.

After the baby is born, variations in physical appearance and symptoms can guide the evaluation. Diagnostic imaging studies, like ultrasound, can be used to check for abnormalities in the brain, heart, abdomen, and kidneys. Screening is crucial in such patients because anomalies can affect multiple organs.

Finally, karyotyping (studying the number and structure of chromosomes in a cell) and microarray testing (which checks for genetic disorders) can confirm trisomy 18 and provide more detail about how the condition affects the cells.

When it comes to monitoring the health of a child with Edwards syndrome, there are several guidelines:

The child’s growth should be assessed regularly.
If there are sucking or swallowing problems, a swallow study might be needed to evaluate the child’s ability to protect the airway.
The child’s cognitive and motor development should be checked at each visit. If needed, early intervention is advisable.
Referrals to an ophthalmologist and audiologist are necessary. An ophthalmologist can check for eye malformations and other issues, while an audiologist can detect hearing loss.

Complete neurological exams are also important to look for muscle tone issues, seizures and more. Other tests include heart ultrasound to check for heart disease, abdominal ultrasound to look for kidney issues and tumors, and orthopedic examination for joint or spine issues. In some cases, a referral to a lung specialist and a sleep study may be recommended. If the child faces dietary challenges or gastroesophageal reflux problems, a gastroenterologist and nutritionist may be beneficial.

Treatment Options for Edwards Syndrome (Trisomy 18)

Edwards syndrome, also known as trisomy 18, is a complex condition with no simple cure. Because the condition often results in high mortality rates in infants, and since it’s challenging to predict which newborns will live beyond their first year, ethical questions can arise around the treatment plan. The key causes of sudden death due to Edwards syndrome are complications related to the nervous system, and respiratory or heart failure. To address this, it is critical to tailor the treatment plan to each child, reflecting the wishes of the parents while always considering the child’s best interest.

In the past, newborns with Edwards syndrome were not resuscitated after birth because the condition was considered fatal. However, newer guidelines from organizations like the American Academy of Pediatrics and the Neonatal Resuscitation Program no longer endorse withholding active management, including resuscitation efforts, for newborns with Edwards syndrome.

Feeding can be a challenge for these babies. Inserting a feeding tube through the nose (nasogastric tube) or directly into the stomach (gastrostomy) can help provide necessary nutrition. Acid reflux is another common issue and can be initially treated with medication. If the problem persists, surgical options may be considered.

Edwards syndrome can also lead to heart failure, and medications like diuretics and digoxin may be used for heart failure management. For more complex heart defects, both palliative (relief-providing) and corrective surgery are recommended.

If an infant with Edwards syndrome becomes sick with infections such as respiratory infections, pneumonia, urinary tract infections, or ear infections, these should be treated as per standard medical protocols.

Orthopedic care might be necessary, especially for cases where the child develops scoliosis due to malformed vertebrae.

Finally, dealing with a diagnosis of Edwards syndrome can be incredibly difficult for families. It’s important that psychosocial support is provided to them. Information about support organizations should also be made available to help families navigate this challenging time.

The condition Edwards syndrome can be mistaken for a variety of other medical issues. These include, but aren’t limited to:

Fetal akinesia sequence (Pena-Shokeir syndrome type I): This is a condition inherited from the parents that results in facial abnormalities, issues with the joints, slow growth in the womb, too much amniotic fluid, and underdeveloped lungs.
Patau syndrome (trisomy 13)
Distal arthrogryposis type I: This condition leads to joint contractures, a condition in which the joints become stiff and difficult to move.
CHARGE syndrome: This syndrome leads to a variety of issues, including eye defects (coloboma), heart malformations, blockages in the nose (choanal atresia), slowed growth, genital and ear abnormalities.
VACTERL association: This group of symptoms involves spinal defects, an imperforate anus (anal atresia), heart defects, abnormal connection between the esophagus and windpipe (tracheoesophageal fistula), a non-fully formed esophagus (esophageal atresia), kidney anomalies, and issues with the limbs.

What to expect with Edwards Syndrome (Trisomy 18)

Approximately 40% of babies sadly pass away during birth, and a third of those who survive are born prematurely. The typical lifespan for those with Edwards syndrome, a genetic disorder, can vary widely, ranging anywhere from 3 days to just over two weeks.

The survival rate for these babies is roughly 60% to 75% after the first week, which decreases to about 20% to 40% after a month, and then remains at around 10% after a year. Just 5% to 10% of those with Edwards syndrome survive longer than this first year.

Interestingly, female infants with this condition tend to live longer than male ones. Also noteworthy is that some cases of Edwards syndrome that present in a form known as “mosaicism” usually have a longer lifespan than the typical form of the disorder.

The primary reasons for mortality usually are heart failure caused by heart defects, and breathing failure. Breathing failure can result from a number of issues including problems like obstructive sleep apnea, high blood pressure in the lungs (pulmonary hypertension), hypoventilation (which is under-breathing or shallow breathing), and central sleep apnea (which happens when your brain doesn’t send proper signals to the muscles that control breathing).

Possible Complications When Diagnosed with Edwards Syndrome (Trisomy 18)

Edwards syndrome, or Trisomy 18, affects the growth and development of a child in several ways. It commonly starts from birth; affected babies usually have a low birth weight and struggle to gain weight and grow as they should. They might have trouble eating, experience discomfort and backflow from food and acid in the stomach, and frequently draw food or vomit into their lungs. There are specific growth charts for this condition to track the child’s progress.

Almost all kids with Edwards syndrome have significant developmental slowdown. They might struggle with cognitive and motor skills, like thinking, understanding, moving, and coordinating their bodies. However, in rare cases, kids with a mosaic type of Edwards syndrome can possess normal intelligence.

The primary cause of death in children with Edwards syndrome is cardio-respiratory failure. This might happen due to birth defects in the heart, inadequate ventilation due to the hypoventilation, breathing issues from central apnea, and underdeveloped lungs.

Edwards syndrome also increases the chance of tumours like the Wilms tumour or kidney tumour, liver cancer, and Hodgkin disease. Kids with Edwards syndrome commonly have a smaller than usual thymus gland and adrenal gland, both of which play essential roles in the body’s immune response and hormone production.

Common effects of Edwards Syndrome include:

Low birth weight and slow growth
Feeding difficulties
Gastroesophageal reflux (food and stomach acid discomfort and backflow)
Frequent lung aspiration (drawing food or vomit into the lungs)
Significant developmental issues affecting the mind and motor skills
Cardio-respiratory failure which could cause death
Increased risk of certain tumours
Smaller than usual thymus and adrenal glands

Preventing Edwards Syndrome (Trisomy 18)

Edwards syndrome, a genetic disorder, unfortunately does not have a specific cure. This often makes it challenging for doctors and parents to decide on the best course of treatment. Parents usually need to make a difficult choice between palliative care, which focuses on providing relief from symptoms and improving quality of life, and extending their child’s life through intensive treatments or surgeries.

Frequently asked questions

Edwards Syndrome, also known as Trisomy 18, is a genetic condition caused by an extra copy of the 18th chromosome in a person's cells. It is an autosomal chromosomal disorder that affects the autosomes, which do not determine a person's sex.

The number of cases of Edwards syndrome varies from 1 in every 3600 to 1 in every 10,000 live births.

Signs and symptoms of Edwards Syndrome (Trisomy 18) include: - Neurologic: Decreased muscle tone at birth followed by increased muscle tone, breathing pauses, seizures, poor feeding, and delayed mental and physical development. - Craniofacial: Small head, narrowing across the temples, bulging at the back of the skull, triangular and asymmetric face with facial paralysis, small eyes, wide-set eyes, fold of skin on the inner corner of the eye, short eyelid openings, a gap in one of the structures of the eyes, cataract, clouding of the eye’s surface, underdeveloped ridge above the eyes, upward or downward slant to the opening between eyelids, and unusual pigmentation of the eyes. - Nose: Prominent bridge of the nose with underdeveloped root of the nose, turned-up nostrils, and narrowing or blockage of the nasal passages. - Oral cavity: Smaller-than-normal lower jaw, small mouth, narrow high-arched palate, cleft lip, and cleft palate. - Ears: Underdeveloped ears, skin tags in front of the ears, low-set or backward-turned ears, and malformed ears. - Skeletal: Severe growth delay, short neck, short breastbone, wide chest with or without small, widely spaced nipples, incomplete bone formation in the collarbone, half-formed or fused bones in the spine, curvature of the spine, indent in the chest, narrow pelvis and limited hip movement, hip dislocation, joint contractures, clenched hands with overlapping fingers, bent fingers, webbing of the fingers, single crease in the palm, bent fifth fingers, underdevelopment of the radius or thumbs, and underdeveloped nails. - Foot problems: Rounded bottom of feet with a prominent heel, clubfoot, bent big toes. - Heart: Heart defects in 90% of patients with Edwards syndrome. These could be a hole in the wall between heart chambers, persisting connection between the aorta and the pulmonary artery, a combination of four heart defects known as tetralogy of Fallot, the aorta overriding the ventricles, narrowing of the aorta, or underdeveloped left side of the heart. More than one heart valve may be affected (most commonly the aorta and pulmonary valve). - Lungs: Underdeveloped lungs, floppy windpipe and voice box, obstructive and central apnea, and early-onset high blood pressure in the arteries to the lungs. - Gastrointestinal: Protrusion of the intestines through a hole near the navel, a blockage in the esophagus with a connection to the windpipe, narrowing of the exit of the stomach, a blockage in the small intestine, twisted intestine, presence of a small bulge in the small intestine, gap between the rectus abdominis muscles, and hernia in the navel. - Genitourinary: Undescended testes, incomplete formation of the urethra and penis, small penis, enlarged clitoris, underdeveloped major labia, abnormal ovaries, a divided uterus, fused kidneys, absent kidney, and kidney swelling. - Central nervous system (affects 30% of cases): Underdeveloped cerebellum, a hole in the skull with brain tissue protruding through, absence of the brain and cranial vault, an increase in fluid in the brain, an anomaly where the brain does not divide properly, a condition where the brain tissue extends into the spinal canal, or an underdeveloped structure that connects the two halves of the brain.

Edwards syndrome (Trisomy 18) typically occurs when there is an extra copy of a part of chromosome 18. This can happen when the chromosome doesn't split correctly during cell division, particularly during the production of eggs or sperm. The extra chromosome usually comes from the mother, and the likelihood of this defect happening increases as the mother gets older.

The other conditions that a doctor needs to rule out when diagnosing Edwards Syndrome (Trisomy 18) are: 1. Fetal akinesia sequence (Pena-Shokeir syndrome type I) 2. Patau syndrome (trisomy 13) 3. Distal arthrogryposis type I 4. CHARGE syndrome 5. VACTERL association

The types of tests needed for Edwards Syndrome (Trisomy 18) include: - Maternal blood tests to check for levels of proteins and hormones - Ultrasound examinations to look for increased thickness in the back of the baby's neck - Non-invasive prenatal testing (NIPT) to study the baby's DNA in the mother's blood - Amniocentesis or chorionic villus sampling to extract fluid or tissue from the womb - Diagnostic imaging studies, such as ultrasound, to check for abnormalities in the brain, heart, abdomen, and kidneys - Karyotyping to study the number and structure of chromosomes in a cell - Microarray testing to check for genetic disorders - Heart ultrasound to check for heart disease - Abdominal ultrasound to look for kidney issues and tumors - Orthopedic examination for joint or spine issues - Neurological exams to check for muscle tone issues and seizures - Referrals to an ophthalmologist and audiologist to check for eye malformations and hearing loss - Referrals to a lung specialist and sleep study if necessary - Referrals to a gastroenterologist and nutritionist for dietary challenges and gastroesophageal reflux problems.

Edwards Syndrome (Trisomy 18) is treated through a tailored treatment plan that reflects the wishes of the parents while considering the child's best interest. Newer guidelines from organizations like the American Academy of Pediatrics and the Neonatal Resuscitation Program recommend active management, including resuscitation efforts, for newborns with Edwards syndrome. Feeding challenges can be addressed by inserting a feeding tube through the nose or directly into the stomach. Acid reflux can be initially treated with medication, and surgical options may be considered if the problem persists. Heart failure can be managed with medications like diuretics and digoxin, and both palliative and corrective surgery are recommended for more complex heart defects. Infections should be treated according to standard medical protocols, and orthopedic care may be necessary for cases of scoliosis. Psychosocial support should also be provided to families dealing with a diagnosis of Edwards syndrome.

The side effects when treating Edwards Syndrome (Trisomy 18) can include: - Complications related to the nervous system, respiratory, or heart failure, which can lead to sudden death - Feeding difficulties, which may require the use of a feeding tube or medication for acid reflux - Heart failure, which may be managed with medications like diuretics and digoxin, or may require surgery - Increased risk of infections, such as respiratory infections, pneumonia, urinary tract infections, or ear infections - Orthopedic issues, such as scoliosis due to malformed vertebrae - Emotional and psychological challenges for families, requiring psychosocial support and access to support organizations.

The prognosis for Edwards Syndrome (Trisomy 18) is generally poor, with a high mortality rate. Approximately 40% of babies with Edwards Syndrome pass away during birth, and a third of those who survive are born prematurely. The survival rate for these babies is roughly 60% to 75% after the first week, which decreases to about 20% to 40% after a month, and then remains at around 10% after a year. Just 5% to 10% of those with Edwards Syndrome survive longer than the first year.

A geneticist or a pediatrician would be appropriate doctors to see for Edwards Syndrome (Trisomy 18).

Chromosomal Abnormalities Genetic Disorders Pregnancy