Edwards Syndrome (Trisomy 18): Genetic Condition, Symptoms and Outlook

What is Edwards syndrome (trisomy 18)?

Edwards syndrome, also known as trisomy 18, is a genetic disorder caused by the presence of an extra chromosome 18. This condition leads to severe developmental and physical abnormalities. Key characteristics of Edwards syndrome include:

● Physical abnormalities: 

These may include low birth weight, a small, abnormally shaped head, clenched fists with overlapping fingers, heart defects, and kidney problems.

● Developmental delays: 

Most affected individuals experience significant delays in growth and development, both physically and mentally.

● Life expectancy:

 Many babies with Edwards syndrome are stillborn or die shortly after birth. The majority of those who survive beyond infancy have severe intellectual disabilities and health problems.

The condition is usually diagnosed through prenatal screening tests, such as ultrasound and amniocentesis, or shortly after birth through physical examination and genetic testing. There is no cure for Edwards syndrome, and treatment focuses on managing symptoms and providing supportive care.

Who does Edwards syndrome (trisomy 18) affect?

Edwards syndrome (trisomy 18) can affect anyone, regardless of gender or ethnic background. It occurs in about 1 in 5,000 live births. However, the likelihood of having a baby with Edwards syndrome increases with the mother's age, particularly in women over the age of 35. Both males and females can be affected, though it is slightly more common in females.

How common is Edwards syndrome (trisomy 18)?

Edwards syndrome (trisomy 18) occurs in about 1 in 5,000 live births. However, the actual incidence of the condition is higher because many affected fetuses are miscarried or stillborn. The risk of having a baby with Edwards syndrome increases with maternal age, particularly in women over 35.

When was Edwards syndrome (trisomy 18) discovered?

Edwards syndrome (trisomy 18) was first identified in 1960 by British geneticist John Hilton Edwards. He described the clinical features of the syndrome and linked them to the presence of an extra chromosome 18. This discovery was significant in the field of genetics and contributed to a better understanding of chromosomal abnormalities and their impact on human development.

What are the symptoms of Edwards syndrome (trisomy 18)?

The symptoms of Edwards syndrome (trisomy 18) are varied and can be severe. Common symptoms include:

Physical abnormalities:

■ Small, abnormally shaped head (microcephaly)

■ Clenched fists with overlapping fingers

■ Low-set ears

■ Small jaw (micrognathia)

■ Rocker-bottom feet

■ Umbilical or inguinal hernia

■ Congenital heart defects

■ Kidney malformations

Growth and developmental issues:

■ Low birth weight

■ Failure to thrive

■ Severe developmental delays

■ Feeding difficulties

Neurological issues:

■ Severe intellectual disability

■ Hypotonia (poor muscle tone)

■ Seizures

Other complications:

■ Respiratory difficulties

■ Frequent infections

Many of these symptoms are apparent at birth or shortly thereafter. The combination and severity of symptoms can vary widely among individuals with Edwards syndrome.

Symptoms of Edwards syndrome (trisomy 18) during pregnancy

During pregnancy, certain signs and symptoms can suggest Edwards syndrome (trisomy 18). These may be detected through prenatal screening and diagnostic tests:

Abnormal ultrasound findings:

● Intrauterine growth restriction (IUGR)

● Polyhydramnios (excess amniotic fluid)

● Congenital heart defects

● Abnormalities in the brain structure

● Omphalocele (an abdominal wall defect)

Abnormal maternal serum screening results:

● Elevated or decreased levels of certain markers, such as alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3)

Non-invasive prenatal testing (NIPT):

● High risk for trisomy 18 based on cell-free fetal DNA analysis in the mother's blood

Amniocentesis or chorionic villus sampling (CVS):

● Confirmation of the diagnosis through genetic testing, revealing an extra chromosome 18 in fetal cells

These signs and tests can help identify the likelihood of Edwards syndrome before birth, allowing for informed decision-making and planning for potential medical care.

Characteristics of Edwards syndrome (trisomy 18) after birth

After birth, infants with Edwards syndrome (trisomy 18) typically exhibit a range of distinctive physical and developmental characteristics, including:

Physical abnormalities:

■ Microcephaly (small head)

■ Prominent occiput (back of the head)

■ Low-set, malformed ears

■ Micrognathia (small jaw)

■ Cleft lip and/or palate

■ Clenched fists with overlapping fingers

■ Rocker-bottom feet

■ Short breastbone (sternum)

■ Widely spaced eyes

Growth issues:

■ Low birth weight

■ Failure to thrive (difficulty gaining weight and growing)

■ Severe growth retardation

Neurological symptoms:

■ Severe intellectual disability

■ Developmental delays (e.g., delays in reaching motor milestones such as rolling over, sitting, and walking)

■ Hypotonia (poor muscle tone)

■ Seizures

Internal organ malformations:

■ Congenital heart defects (e.g., ventricular septal defect, atrial septal defect, patent ductus arteriosus)

■ Kidney abnormalities

■ Gastrointestinal malformations (e.g., omphalocele, diaphragmatic hernia)

Other complications:

■ Feeding difficulties, often requiring tube feeding

■ Respiratory issues, including apnea and chronic lung disease

■ Frequent infections due to a weakened immune system

The combination and severity of these characteristics can vary widely among individuals with Edwards syndrome. Most affected infants require extensive medical care and support due to the complexity and severity of their symptoms.

Severe symptoms of Edwards syndrome (trisomy 18)

Severe symptoms of Edwards syndrome (trisomy 18) can significantly impact the health and quality of life of affected individuals. These symptoms include:

Congenital heart defects:

● Ventricular septal defect (VSD)

● Atrial septal defect (ASD)

●Patent ductus arteriosus (PDA)

● Tetralogy of Fallot

Respiratory problems:

● Apnea (temporary cessation of breathing)

● Chronic lung disease

● Frequent respiratory infections

Neurological impairments:

● Severe intellectual disability

● Developmental delays (e.g., inability to sit, stand, or walk)

● Seizures

Gastrointestinal issues:

● Omphalocele (abdominal organs protrude outside the body)

● Esophageal atresia (esophagus does not connect to the stomach)

● Feeding difficulties, often requiring tube feeding

Kidney abnormalities:

● Horseshoe kidney (kidneys are fused together)

● Hydronephrosis (swelling of a kidney due to a build-up of urine)

● Other structural kidney defects

Musculoskeletal problems:

● Rocker-bottom feet

● Clenched fists with overlapping fingers

● Scoliosis (curvature of the spine)

Growth and developmental issues:

● Severe failure to thrive

● Poor muscle tone (hypotonia)

Immune system deficiencies:

● Increased susceptibility to infections

These severe symptoms typically result in a high mortality rate in infancy or early childhood, with many affected individuals passing away within the first few months of life due to complications from these severe abnormalities.

What causes Edwards syndrome (trisomy 18)?

Edwards syndrome (trisomy 18) is caused by the presence of an extra copy of chromosome 18 in the cells of the body. This genetic disorder typically occurs due to errors during the formation of reproductive cells (eggs and sperm). There are a few mechanisms by which this can happen:

Nondisjunction:

 The most common cause is a nondisjunction event during meiosis, the process of cell division that produces eggs and sperm. Nondisjunction results in a reproductive cell with an extra copy of chromosome 18. When this cell combines with a normal cell from the other parent, the resulting embryo has three copies of chromosome 18 instead of the usual two.

Mosaic trisomy 18:

 In some cases, the error in chromosome number occurs after fertilization, during the early cell divisions of the embryo. This can lead to a mosaic form of trisomy 18, where some cells have the normal number of chromosomes (46), while others have an extra chromosome 18 (47).

Translocation trisomy 18:

 A rare form occurs when part of chromosome 18 attaches to another chromosome (translocation). Individuals with translocation trisomy 18 have two normal copies of chromosome 18 and extra material from chromosome 18 attached to another chromosome. This can occur either spontaneously or be inherited from a parent who carries a balanced translocation.

The presence of the extra chromosome 18 disrupts normal development, leading to the characteristic symptoms and severe abnormalities associated with Edwards syndrome.

How is Edwards syndrome (trisomy 18) diagnosed?

Edwards syndrome (trisomy 18) can be diagnosed before or after birth through a combination of screening tests and diagnostic procedures:

Prenatal Diagnosis

1. Screening Tests:

■ Ultrasound:

 Can detect physical abnormalities associated with Edwards syndrome, such as growth restriction, heart defects, or other structural anomalies.

■ Maternal Serum Screening:

 Measures levels of certain substances in the mother’s blood (e.g., alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol). Abnormal levels may indicate an increased risk of chromosomal abnormalities, including trisomy 18.

■ Non-Invasive Prenatal Testing (NIPT):

 Analyzes fetal DNA circulating in the mother’s blood to detect the risk of trisomy 18 with high accuracy.

2. Diagnostic Tests:

■ Chorionic Villus Sampling (CVS):

 Involves taking a small sample of placental tissue to analyze the fetal chromosomes. This test is usually performed between the 10th and 13th weeks of pregnancy.

■ Amniocentesis: 

Involves extracting a small amount of amniotic fluid to analyze the fetal chromosomes. This test is usually performed between the 15th and 20th weeks of pregnancy. Both CVS and amniocentesis provide a definitive diagnosis by identifying the extra chromosome 18.

Postnatal Diagnosis

1. Physical Examination: 

Newborns with Edwards syndrome often exhibit characteristic physical features, such as low birth weight, microcephaly, clenched fists with overlapping fingers, and rocker-bottom feet.

2. Chromosomal Analysis:

■ Karyotyping:

 Analyzes the chromosomal composition of cells from the baby’s blood or other tissues to detect the presence of an extra chromosome 18.

■ Fluorescence In Situ Hybridization (FISH): 

A rapid test that uses fluorescent probes to detect specific chromosomes, including chromosome 18.

3. Additional Tests: 

To assess the extent of organ involvement and other abnormalities, such as echocardiograms for heart defects and imaging studies for other structural anomalies.

Early and accurate diagnosis allows for appropriate medical care, family counseling, and decision-making regarding the management of the condition.

What tests diagnose Edwards syndrome (trisomy 18)?

To diagnose Edwards syndrome (trisomy 18), the following tests are used:

Prenatal Tests

1. Screening Tests:

● Ultrasound: 

Can identify physical abnormalities and signs indicative of Edwards syndrome, such as growth restriction and heart defects.

● Maternal Serum Screening:

 Measures biomarkers in the mother’s blood (e.g., alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol) to assess the risk of chromosomal abnormalities.

● Non-Invasive Prenatal Testing (NIPT):

 Analyzes fetal DNA in the mother’s blood to screen for trisomy 18 with high accuracy.

2. Diagnostic Tests:

● Chorionic Villus Sampling (CVS): 

Takes a sample of placental tissue to analyze fetal chromosomes for trisomy 18. Typically performed between 10 and 13 weeks of pregnancy.

● Amniocentesis:

 Collects a sample of amniotic fluid to analyze fetal chromosomes for trisomy 18. Usually performed between 15 and 20 weeks of pregnancy.

Postnatal Tests

1. Physical Examination:

 Identifies characteristic features of Edwards syndrome, such as microcephaly, clenched fists, and rocker-bottom feet.

2. Chromosomal Analysis:

● Karyotyping: 

Analyzes the number and structure of chromosomes from a blood sample or other tissues to confirm the presence of an extra chromosome 18.

● Fluorescence In Situ Hybridization (FISH):

 A rapid test that uses fluorescent probes to detect the presence of the extra chromosome 18.

These tests help confirm a diagnosis and assess the severity of the condition, guiding medical management and family counseling.

How is Edwards syndrome (trisomy 18) treated?

Edwards syndrome (trisomy 18) has no cure, so treatment focuses on managing symptoms and providing supportive care to improve the quality of life. The approach varies depending on the severity of the symptoms and the specific needs of the individual. Key aspects of treatment include:

Medical Care:

■ Cardiac Care: 

Management of congenital heart defects, which may include medications or surgery.

■ Respiratory Support:

 Treatment for breathing difficulties, which may involve oxygen therapy or mechanical ventilation.

■ Feeding Support: 

Assistance with feeding, which might include tube feeding if the baby has difficulties feeding by mouth.

■ Nutritional Support: 

Ensuring proper nutrition through specialized feeding plans and supplements if needed.

Developmental Support:

■ Physical Therapy: 

To help with motor skills and muscle tone.

■ Occupational Therapy: 

To assist with daily living activities and improve overall functioning.

■ Speech Therapy: 

To support communication skills, if applicable.

Monitoring and Management of Complications:

■ Regular follow-ups to monitor and manage other health issues, such as kidney problems or infections.

■ Coordination with specialists for various aspects of care, such as cardiology, nephrology, and pulmonology.

Palliative Care:

■ Providing comfort care and pain management to improve quality of life, especially for infants with severe symptoms.

■ Family support and counseling to help cope with the emotional and practical challenges of caring for a child with a severe, life-limiting condition.

End-of-Life Care:

■ For those with severe forms of Edwards syndrome, end-of-life care focuses on ensuring comfort and dignity.

The specific treatment plan is tailored to each individual's needs and is often developed by a team of healthcare professionals, including pediatricians, specialists, and therapists, in collaboration with the family.

How can I reduce my risk of having a child with Edwards syndrome (trisomy 18)?

While not all risk factors for Edwards syndrome (trisomy 18) can be controlled, there are steps you can take to help manage and potentially reduce your risk:

Prenatal Screening and Diagnostic Testing:

● Early Screening: 

Consider non-invasive prenatal testing (NIPT) or maternal serum screening to assess the risk of trisomy 18. These tests can help identify higher-risk pregnancies early on.

● Diagnostic Tests:

 If screening indicates a higher risk, diagnostic tests like chorionic villus sampling (CVS) or amniocentesis can provide definitive information about the presence of trisomy 18.

Genetic Counseling:

● Preconception Counseling:

 If you have a family history of genetic disorders or are over the age of 35, consider genetic counseling before conception. A genetic counselor can help assess your risk and provide information about genetic testing options.

Maternal Age:

● Understand the Risk: 

Be aware that advanced maternal age (35 or older) is associated with a higher risk of chromosomal abnormalities. If you are in this age group, discussing your options with a healthcare provider can be beneficial.

Healthy Lifestyle:

● Maintain Good Health: 

Overall health can impact pregnancy outcomes. Eating a balanced diet, exercising regularly, avoiding harmful substances, and managing chronic conditions can contribute to a healthier pregnancy.

Avoid Harmful Substances:

● No Smoking or Alcohol: 

Avoid smoking and alcohol during pregnancy, as these can affect fetal development.

Regular Prenatal Care:

● Attend Prenatal Appointments: 

Regular visits with your healthcare provider can help monitor the health of both you and your baby, allowing for early detection and management of any potential issues.

While these measures can help manage risk, they cannot completely eliminate the possibility of Edwards syndrome, as the condition is often due to random chromosomal errors that occur during the formation of reproductive cells.

What can I expect if I have a child with Edwards syndrome (trisomy 18)?

Having a child with Edwards syndrome (trisomy 18) can be challenging due to the severe nature of the condition. Here’s what you might expect:

Health Challenges:

■ Medical Complications: 

Your child may face significant health issues such as congenital heart defects, respiratory problems, and feeding difficulties. These conditions often require ongoing medical care and may involve specialists.

■ Frequent Medical Visits:

 Regular visits to healthcare providers for monitoring and managing symptoms will be necessary. This might include cardiologists, pulmonologists, and other specialists.

Developmental Delays:

■ Severe Delays: 

Your child will likely experience severe developmental delays and intellectual disabilities. They may not achieve typical milestones like sitting, standing, or walking.

Supportive Care:

■ Physical and Occupational Therapy:

 Your child might benefit from therapies designed to support their physical and developmental needs.

■ Feeding Support:

 Special feeding techniques or tube feeding may be necessary if your child has difficulty eating.

Palliative and End-of-Life Care:

■ Comfort Care: 

For children with severe symptoms, palliative care focuses on comfort and quality of life. This may involve managing pain and other symptoms to ensure your child’s comfort.

■ End-of-Life Considerations: 

Unfortunately, many children with Edwards syndrome have a shortened life expectancy. End-of-life care and decisions will be a crucial part of managing the condition.

Emotional and Practical Support:

■ Family Support: 

The emotional and practical demands of caring for a child with a severe condition can be significant. Seeking support from family, friends, or support groups can be helpful.

■ Counseling Services:

 Psychological support or counseling for you and your family may be beneficial in coping with the challenges and emotional impact.

Quality of Life:

■ Focus on Comfort:

 The goal is to ensure your child’s comfort and to provide the best possible quality of life given the circumstances. This includes managing symptoms and supporting their physical and emotional needs.

Every child with Edwards syndrome is unique, so the specific needs and experiences will vary. Working closely with a team of healthcare professionals can help manage the condition and provide the best care for your child.

When should I see my healthcare provider?

You should see your healthcare provider in the following situations:

Prenatal Care:

● Early and Regular Visits: 

Schedule regular prenatal appointments to monitor the health of both you and your baby. If you are over 35 or have risk factors for chromosomal abnormalities, discuss screening and diagnostic options early in pregnancy.

● Abnormal Test Results:

 If any prenatal screening or diagnostic tests suggest a risk or confirm a diagnosis of Edwards syndrome, follow up with your provider for further evaluation and guidance.

Postnatal Care:

● After Birth:

 If your baby is diagnosed with Edwards syndrome or exhibits any of the characteristic symptoms, contact your healthcare provider immediately to begin a plan for managing the condition.

● Ongoing Medical Needs: 

Regular follow-ups are essential to manage the various health issues associated with Edwards syndrome, such as heart defects, respiratory problems, and feeding difficulties.

Health Concerns:

● New Symptoms:

 If you or your baby notice new or worsening symptoms, such as difficulty breathing, feeding issues, or signs of distress, seek medical attention promptly.

● Developmental Monitoring: 

Regular appointments with specialists like cardiologists, pulmonologists, and developmental therapists can help manage the complex needs of a child with Edwards syndrome.

Emotional and Practical Support:

● Family Counseling: 

Seek counseling or support services if you need help coping with the emotional and practical aspects of caring for a child with a severe condition.

Regular communication with your healthcare provider and a multidisciplinary care team is crucial to address the complex needs associated with Edwards syndrome and to ensure the best possible care for your child.

When should I go to ER?

You should go to the emergency room (ER) if you or your child with Edwards syndrome (trisomy 18) experience any of the following urgent situations:

Severe Breathing Issues:

■ Difficulty breathing, severe wheezing, or persistent apnea (pauses in breathing).

■ Cyanosis (bluish discoloration of the skin or lips), indicating inadequate oxygen.

Cardiac Emergencies:

■ Signs of heart failure, such as severe chest pain, rapid or irregular heartbeats, or significant swelling in the extremities.

Severe Feeding Problems:

■ Inability to feed, severe vomiting, or signs of dehydration.

Neurological Issues:

■ Sudden seizures, severe lethargy, or loss of consciousness.

Signs of Infection:

■ High fever, severe pain, or other symptoms of infection that don’t improve with home treatment.

Emergency Situations:

■ Any sudden or severe symptoms that may indicate a life-threatening condition, such as a sudden change in behavior or health status.

In general, if you have concerns that require immediate attention or if the symptoms appear life-threatening, seeking emergency medical care is appropriate. Always trust your instincts and err on the side of caution when dealing with serious health issues.

What questions should I ask my doctor?

When discussing Edwards syndrome (trisomy 18) with your doctor, consider asking the following questions to better understand the condition and the care needed:

For Prenatal Concerns:

● What are the options for prenatal screening and diagnostic tests, and when should they be performed?

● What does a positive screening result mean, and how accurate are these tests?

● If diagnostic tests confirm Edwards syndrome, what are the implications for the pregnancy and the baby’s health?

For Postnatal Concerns:

● What are the immediate medical needs and treatments required for my baby after birth?

● What are the common symptoms and complications of Edwards syndrome, and how can they be managed?

● What specialists will be involved in my baby's care, and how often will we need to see them?

For Ongoing Care:

● What are the expected developmental milestones and limitations for a child with Edwards syndrome?

● What therapies or interventions might benefit my child (e.g., physical, occupational, or speech therapy)?

● How can we best manage feeding and nutritional needs?

For Support and Resources:

● What resources are available for families coping with Edwards syndrome (e.g., support groups, counseling)?

● Are there any specific guidelines or strategies for home care and symptom management?

● What should we do in case of an emergency or if my baby’s condition worsens?

For Long-Term Planning:

● What is the typical prognosis and life expectancy for a child with Edwards syndrome?

● What palliative care options are available, and when should we consider them?

These questions can help you gather essential information and make informed decisions about managing your child’s care and planning for the future.