Edwards Syndrome (Trisomy 18)

Overview

Plain-Language Overview

Edwards Syndrome, also known as Trisomy 18, is a genetic condition caused by an extra copy of chromosome 18. It affects many parts of the body and leads to severe developmental delays and physical abnormalities. Babies with this syndrome often have a small head, clenched fists, and heart defects. Most infants with Edwards Syndrome have a shortened life expectancy, with many not surviving beyond the first year. The condition is rare and occurs in about 1 in 5,000 live births.

Clinical Definition

Edwards Syndrome is a chromosomal disorder characterized by the presence of a full or partial extra chromosome 18, resulting in Trisomy 18. This genetic anomaly leads to multiple congenital malformations including microcephaly, prominent occiput, micrognathia, and overlapping fingers with clenched fists. Cardiac defects such as ventricular septal defects and patent ductus arteriosus are common. Neurologically, affected infants exhibit severe intellectual disability and developmental delay. Growth retardation is evident both prenatally and postnatally. The syndrome is associated with a high rate of fetal loss and neonatal mortality, with less than 10% surviving beyond the first year. Diagnosis is confirmed by karyotyping or chromosomal microarray analysis. The condition is typically sporadic, with advanced maternal age being a risk factor. There is no cure, and management is supportive and symptomatic.

Inciting Event

The inciting event is a meiotic nondisjunction during gametogenesis leading to an extra chromosome 18.

Latency Period

none

Diagnostic Delay

Prenatal diagnosis may be delayed due to subtle or nonspecific ultrasound findings early in pregnancy.
Postnatal diagnosis can be delayed if characteristic physical features are mild or overlooked.
Limited access to genetic testing can also contribute to delayed diagnosis.

Clinical Presentation

Signs & Symptoms

Severe intellectual disability and developmental delay.
Feeding difficulties due to poor sucking and swallowing.
Respiratory distress from central apnea or structural anomalies.
Failure to thrive with marked growth retardation.
Frequent seizures.

History of Present Illness

Affected infants often present with growth retardation and multiple congenital anomalies.
Common features include micrognathia, clenched fists with overlapping fingers, and rocker-bottom feet.
Severe feeding difficulties and respiratory problems are frequently reported.

Past Medical History

A history of previous pregnancies with chromosomal abnormalities or miscarriages is relevant.
Maternal health conditions such as advanced age increase risk.
No specific past medical conditions in the infant influence the course as it is a congenital disorder.

Family History

Most cases are sporadic with no family history due to random nondisjunction.
Rarely, familial translocations involving chromosome 18 can increase recurrence risk.
A family history of chromosomal disorders may be relevant.

Physical Exam Findings

Presence of micrognathia with a small, recessed jaw.
Clenched hands with overlapping fingers, especially the index finger over the third finger.
Prominent occiput noted on head examination.
Rocker-bottom feet with a convex sole.
Low-set, malformed ears.

Diagnostic Workup

Diagnostic Criteria

Diagnosis of Edwards Syndrome requires identification of the characteristic trisomy 18 on chromosomal analysis, typically via karyotyping. Clinical features supporting diagnosis include intrauterine growth restriction, microcephaly, clenched fists with overlapping fingers, congenital heart defects, and distinctive craniofacial abnormalities such as micrognathia and low-set ears. Prenatal ultrasound findings and elevated maternal serum markers may suggest the diagnosis, but definitive confirmation depends on cytogenetic testing.

Pathophysiology

Key Mechanisms

Edwards syndrome is caused by trisomy 18, an extra copy of chromosome 18 leading to abnormal cellular development and organ malformations.
The presence of an extra chromosome disrupts normal gene dosage, resulting in widespread developmental abnormalities.
This chromosomal imbalance causes severe congenital defects affecting the heart, kidneys, and central nervous system.

Involvement	Details
Organs	Heart commonly exhibits structural defects including ventricular septal defects and patent ductus arteriosus.
	Kidneys may show malformations such as horseshoe kidney or cystic dysplasia.
	Brain abnormalities include microcephaly and structural malformations contributing to neurological impairment.
Tissues	Cardiac tissue is frequently affected, leading to congenital heart defects such as ventricular septal defects.
Tissues	Neural tissue abnormalities contribute to severe intellectual disability and developmental delay.
Cells	Trisomic cells containing an extra chromosome 18 cause the multisystem abnormalities seen in Edwards syndrome.
Chemical Mediators	Apoptotic mediators contribute to abnormal development and organ malformations in Edwards syndrome.

Treatment

Pharmacological Treatments

Supportive care medications
- Mechanism: Symptomatic management of complications such as seizures or heart failure
- Side effects: Vary depending on medication used

Non-pharmacological Treatments

Provision of multidisciplinary supportive care including physical, occupational, and speech therapy to improve quality of life.
Genetic counseling for families to understand recurrence risk and implications.
Palliative care focusing on comfort and symptom management due to poor prognosis.

Prevention

Pharmacological Prevention

none

Non-pharmacological Prevention

Prenatal genetic counseling for at-risk couples.
Use of prenatal screening and diagnostic testing such as chorionic villus sampling or amniocentesis.
Avoidance of known teratogens and optimization of maternal health.

Outcome & Complications

Complications

Severe cardiorespiratory failure due to congenital heart disease and apnea.
Recurrent infections from impaired swallowing and aspiration.
Failure to thrive leading to malnutrition.
Neurological complications including seizures and hypotonia.

Short-term Sequelae	Long-term Sequelae
Neonatal respiratory distress requiring supportive care. Early onset feeding difficulties necessitating tube feeding. Frequent hospitalizations for cardiac and respiratory complications.	Profound intellectual disability with limited developmental progress. Chronic cardiac insufficiency from congenital defects. Persistent growth failure and failure to thrive. Severe neuromuscular impairment with hypotonia and contractures.

Differential Diagnoses

Edwards Syndrome (Trisomy 18) versus Down Syndrome (Trisomy 21)

Edwards Syndrome (Trisomy 18)	Down Syndrome (Trisomy 21)
Severe intellectual disability and growth retardation	Upward slanting palpebral fissures and epicanthal folds
Clenched hands with overlapping fingers and prominent occiput	Single transverse palmar crease
Rocker-bottom feet and congenital heart defects like VSD	Hypotonia with mild to moderate intellectual disability

Edwards Syndrome (Trisomy 18) versus Patau Syndrome (Trisomy 13)

Edwards Syndrome (Trisomy 18)	Patau Syndrome (Trisomy 13)
Prominent occiput and micrognathia without holoprosencephaly	Presence of holoprosencephaly and cleft lip/palate
Clenched hands with overlapping fingers	Polydactyly with postaxial extra digits
Rocker-bottom feet deformity	Severe microphthalmia or anophthalmia

Edwards Syndrome (Trisomy 18) versus Turner Syndrome (45,X)

Edwards Syndrome (Trisomy 18)	Turner Syndrome (45,X)
Multiple congenital anomalies including clenched hands and micrognathia	Short stature with webbed neck and shield chest
Severe growth retardation and rocker-bottom feet	Lymphedema of hands and feet at birth
Presence of cardiac defects like VSD and PDA	Primary amenorrhea and gonadal dysgenesis