Edwards Syndrome: Symptoms, Types, Causes and Treatment

Edwards syndrome, also known as trisomy 18, is the second most common autosomal chromosomal disorder after Down syndrome. It brings immense challenges not only for affected children but also for their families and healthcare teams. Characterized by a wide array of congenital anomalies and a high early mortality rate, Edwards syndrome demands a nuanced understanding of its symptoms, genetic mechanisms, and approaches to care. In this article, we will explore the key symptoms, different types, underlying causes, and current treatment strategies for Edwards syndrome, drawing on recent research and clinical case studies.

Symptoms of Edwards Syndrome

Edwards syndrome is marked by a distinctive set of clinical features that affect nearly every organ system. Recognizing these symptoms early is essential for diagnosis and for guiding appropriate care decisions. While the presentation can vary in severity, certain signs are characteristic and guide clinicians toward a diagnosis of trisomy 18.

Symptom	System Affected	Frequency/Severity	Source(s)
Cardiac defects	Cardiovascular	Very common, severe	1, 10
Growth delay	General/Development	Universal, pronounced	1, 4, 5
Craniofacial anomalies	Craniofacial	Common	1, 10
Clenched hands	Musculoskeletal	Frequent, classic sign	1, 10
Rocker-bottom feet	Musculoskeletal	Common	1, 10
Intellectual disability	Neurological	Severe, universal	2, 4, 5
Organ malformations	Multiple	Frequent, life-threatening	1, 6, 10
Tumor risk	Liver, kidney	Increased for some tumors	2
Endocrinopathies	Endocrine	Occasional	6
Developmental delay	Neurological	Universal, severe	8

Table 1: Key Symptoms

Cardiac and Organ Abnormalities

Heart defects are the most common and severe problems seen in Edwards syndrome, often including ventricular septal defect (VSD), atrial septal defect (ASD), patent ductus arteriosus (PDA), and tricuspid valve malformations. These cardiac issues are a leading cause of early death 10. Other vital organs such as the kidneys, brain, and gastrointestinal tract are also frequently affected, contributing to high neonatal mortality 4, 10.

Growth and Developmental Delays

Children with Edwards syndrome typically exhibit significant growth retardation, both prenatally and postnatally. Developmental progress is severely delayed, with most children unable to reach milestones like sitting or walking without extensive support 1, 4, 5, 8.

Craniofacial and Musculoskeletal Features

Distinct facial features—such as microcephaly, micrognathia (small jaw), low-set ears, and microphthalmia (small eyes)—are commonly observed 1, 10. Clenched hands with overlapping fingers and rocker-bottom feet are considered hallmark signs 1, 10.

Neurological and Endocrine Manifestations

Severe intellectual disability is universal among survivors 2, 4, 5. Some rare neurological findings include holoprosencephaly (HPE), convulsions, and various endocrinopathies like central diabetes insipidus, hypothyroidism, and growth hormone deficiency 6.

Tumor Profile

Although rare, certain tumors such as hepatoblastomas (liver) and nephroblastomas (kidney) have been reported more frequently in children with Edwards syndrome. Interestingly, the tumor profile in trisomy 18 differs from other trisomies, such as Down syndrome 2.

Types of Edwards Syndrome

Not every case of Edwards syndrome is identical. The genetic mechanisms underlying the condition can vary, leading to differences in severity, prognosis, and clinical presentation. Understanding these types is crucial for prognosis and family counseling.

Type	Chromosome Abnormality	Clinical Severity	Source(s)
Full Trisomy 18	Complete extra chromosome 18 in all cells	Most severe	4, 10
Mosaic Trisomy 18	Extra chromosome 18 in some cells only	Variable, often milder	4
Partial Trisomy 18	Duplication of a segment of chromosome 18	Mildest, variable	1, 3

Table 2: Types of Edwards Syndrome

Full Trisomy 18

This is the classic and most common form, resulting from the presence of an extra copy of chromosome 18 in every cell. It is associated with the most severe symptoms and the poorest prognosis. More than 90% of affected infants die within the first year due to vital organ dysfunction 4, 10.

Mosaic Trisomy 18

In mosaic trisomy 18, only some cells carry the extra chromosome, while others are normal. This mosaicism often results in a milder or atypical clinical presentation, depending on the proportion and distribution of trisomic cells. Some individuals with mosaic trisomy 18 may survive into adolescence or adulthood, although significant disabilities are still present 4.

Partial Trisomy 18

This rare form involves duplication of only a portion of chromosome 18, rather than the entire chromosome. The clinical presentation can range from very mild to near-classic features, depending on which segment is duplicated. For example, duplications involving the 18q11.2-q12 region are often milder and associated with a better prognosis, while duplications of other regions can be much more severe 1, 3.

Causes of Edwards Syndrome

Understanding the root causes of Edwards syndrome helps families and clinicians comprehend why this complex disorder occurs and informs genetic counseling decisions.

Cause	Description	Frequency/Impact	Source(s)
Nondisjunction	Failure of chromosomes to separate during meiosis	Most common cause	4, 5
Parental Age	Advanced maternal age increases risk	Significant factor	5
Genetic Mosaicism	Post-zygotic error, some normal cells	Variable severity	4
Partial Duplication	Translocation or duplication of chromosome segment	Rare	1, 3

Table 3: Causes of Edwards Syndrome

Chromosomal Nondisjunction

The vast majority of Edwards syndrome cases are caused by a nondisjunction event during egg or sperm formation, resulting in an extra chromosome 18 in the fertilized egg. This error is random and not typically inherited 4, 5.

Advanced Maternal Age

There is a recognized association between increased maternal age and the risk of nondisjunction events leading to trisomy 18. This mirrors the pattern seen in other chromosomal aneuploidies, such as Down syndrome 5.

Mosaicism

In mosaic trisomy 18, the chromosomal abnormality arises after fertilization. Some cells end up with an extra chromosome 18, while others remain normal. The proportion of affected cells determines the severity of symptoms 4.

Partial Duplication and Translocation

Rarely, only a segment of chromosome 18 is duplicated due to structural rearrangements like translocations. The clinical severity is determined by the specific genes duplicated. Certain segments have been associated with more severe neurological or physical symptoms 1, 3.

Treatment of Edwards Syndrome

While there is no cure for Edwards syndrome, treatment focuses on maximizing quality of life, addressing immediate medical needs, and supporting families through difficult decisions. Management strategies require careful, individualized planning due to the complexity and severity of the condition.

Treatment	Purpose/Approach	Challenges	Source(s)
Supportive care	Symptom management, comfort	Short life expectancy	4, 7
Surgical intervention	Correct life-threatening anomalies	Ethical dilemmas	7, 9, 10
Physiotherapy	Aid in development, mobility	Limited improvement	8
Ethical decision-making	Family-centered care planning	Withholding/withdrawing treatment	7

Table 4: Treatment Approaches

Supportive and Palliative Care

Given the poor prognosis, most interventions are supportive. These may include feeding support, respiratory care, and management of infections or seizures. Comfort and quality of life are prioritized 4, 7.

Surgical and Medical Interventions

Life-threatening anomalies, such as major heart defects or gastrointestinal malformations, sometimes prompt consideration of surgical correction. However, the high risk of complications and the overall prognosis often lead clinicians and families to opt for less aggressive approaches. Rapid diagnosis via karyotyping helps avoid unnecessary invasive procedures 7. When surgery is performed, careful anesthetic management is required due to the high risk posed by cardiac and airway abnormalities 9, 10.

Physiotherapy

For children who survive beyond infancy, physiotherapy can help improve posture, movement, and respiratory status. While such interventions may aid in reaching some developmental milestones, their overall impact is limited by the underlying neurological deficits 8.

Ethical and Family-Centered Decision-Making

Decisions about invasive treatments require sensitive, open discussions between healthcare providers and families. The ethical considerations are complex, given the short life expectancy and severity of disabilities. Withholding or withdrawing aggressive treatment is sometimes the most compassionate choice 7.

Conclusion

Edwards syndrome is a devastating chromosomal disorder, but improved understanding and compassionate care can make a meaningful difference for affected children and their families. Here are the key points discussed in this article:

• Symptoms: Include distinctive craniofacial features, severe cardiac and organ malformations, growth and developmental delays, and a unique tumor profile.
• Types: Full trisomy 18 is most common and severe; mosaic and partial forms may result in milder symptoms.
• Causes: Most cases result from random chromosomal nondisjunction, with increased risk linked to advanced maternal age. Mosaic and partial forms reflect different genetic mechanisms.
• Treatment: Focuses on supportive care, symptom management, and family-centered ethical decision-making. Surgical and therapeutic interventions are individualized and may be limited by prognosis and quality of life considerations.

By deepening our understanding of Edwards syndrome, we can foster better medical, ethical, and emotional support for those affected by this challenging condition.