Trisomy 18 Syndrome

Trisomy 18 Syndrome: Symptoms, Causes, Types, Diagnosis, and Treatments

Introduction

Trisomy 18 syndrome, also known as Edwards syndrome, is a rare and severe genetic disorder caused by the presence of an extra chromosome 18 in a person’s cells. This chromosomal anomaly leads to profound developmental and physical abnormalities. Named after Dr. John Hilton Edwards, who first described the condition in 1960, Trisomy 18 is the second most common autosomal trisomy after Down syndrome (Trisomy 21).

Despite its rarity, awareness of Trisomy 18 Syndrome is crucial for early diagnosis, management, and family counseling. This article explores the symptoms, causes, types, diagnostic methods, and treatment options available for Trisomy 18 syndrome in depth.

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What is Trisomy 18 Syndrome?

Humans typically have 23 pairs of chromosomes, with one chromosome of each pair inherited from each parent. Trisomy 18 syndrome occurs when there is an extra (third) copy of chromosome 18 instead of the usual pair. This extra chromosome disrupts normal development and causes multiple physical and intellectual disabilities.

The condition primarily affects females (approximately 3:1 female to male ratio), and most affected pregnancies result in miscarriage or stillbirth. The survival rate beyond infancy is low, but some children with Trisomy 18 live into early childhood or, in rare cases, longer.

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Causes of Trisomy 18 Syndrome

Genetic Cause

Trisomy 18 results from nondisjunction during cell division, a process where chromosomes fail to separate properly. This error leads to an egg or sperm cell with an extra chromosome 18. When fertilization occurs, the resulting embryo has three copies of chromosome 18 in its cells instead of two.

Types of Trisomy 18 Based on Genetic Variation

1. Full Trisomy 18 Syndrome:
   The most common form, where every cell in the body has an extra chromosome 18. It accounts for about 94% of cases.
2. Mosaic Trisomy 18 Syndrome:
   In this form, only some cells have the extra chromosome, while others are normal. This results from nondisjunction occurring after fertilization (post-zygotic error). Mosaicism can cause milder symptoms, depending on the proportion of affected cells.
3. Partial Trisomy 18 Syndrome:
   Here, only a part of chromosome 18 is duplicated, leading to a subset of Trisomy 18 features. This form is less common and usually results from a chromosomal translocation in one of the parents.

Risk Factors

• Maternal Age: The risk of Trisomy 18 increases with maternal age, particularly over 35 years.
• Parental Chromosomal Abnormalities: If a parent carries a balanced translocation involving chromosome 18, there is a higher risk of passing on an unbalanced form causing partial trisomy.

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Symptoms of Trisomy 18 Syndrome

Trisomy 18 syndrome presents with a broad spectrum of clinical features due to multi-system involvement. Symptoms are often severe and involve growth retardation, intellectual disability, and multiple congenital anomalies.

Physical Characteristics

• Low Birth Weight: Babies are often small for gestational age.
• Small, Abnormally Shaped Head (Microcephaly): The head is smaller and sometimes has an unusual shape.
• Prominent Occiput: The back of the head may be unusually prominent.
• Clenched Hands with Overlapping Fingers: Fingers overlap with the index finger overlapping the middle finger.
• Rocker-Bottom Feet: The soles of the feet have a prominent rounded heel.
• Micrognathia: Small jaw.
• Low-Set, Abnormally Shaped Ears.
• Small Mouth and Cleft Palate (in some cases).
• Short Neck.

Organ and System Involvement

• Cardiac Defects: Over 90% of babies with Trisomy 18 have congenital heart defects such as ventricular septal defects (VSD), atrial septal defects (ASD), or patent ductus arteriosus (PDA).
• Kidney Abnormalities: Horseshoe kidney and other structural abnormalities are common.
• Gastrointestinal Issues: Including intestinal malformations, omphalocele (abdominal wall defect), and feeding difficulties.
• Respiratory Problems: Due to underdeveloped lungs or apnea episodes.
• Neurological Symptoms: Severe intellectual disability, hypotonia (poor muscle tone), seizures, and delayed development.
• Growth Retardation: Both before and after birth.
• Other Features: Clubfeet, hernias, and undescended testes in males.

Developmental and Cognitive Effects

Children with Trisomy 18 usually experience profound developmental delays. Most affected infants are non-verbal and have limited motor skills. Cognitive impairments are severe, with very few surviving beyond early childhood.

Prognosis

The prognosis is generally poor. About 50% of infants die within the first week of life, and up to 90% by the end of the first year due to complications like cardiac and respiratory failure.

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Types of Trisomy 18 Syndrome

As noted, Trisomy 18 exists in three main forms, which vary in severity.

1. Full Trisomy 18

• All cells contain three copies of chromosome 18.
• Most severe presentation.
• Typically leads to death within the first year.
• Most common form (approx. 94% of cases).

2. Mosaic Trisomy 18

• Some cells have normal chromosomes; others have the extra chromosome 18.
• Symptoms are usually milder.
• Life expectancy may be longer depending on the proportion of trisomic cells.
• Often diagnosed later due to milder clinical features.

3. Partial Trisomy 18

• Only a segment of chromosome 18 is duplicated.
• Clinical features vary depending on which genes are involved.
• Usually inherited from a parent with balanced translocation.
• Symptoms can range from mild to severe.

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Diagnosis of Trisomy 18 Syndrome

Early diagnosis is crucial for managing Trisomy 18 syndrome and providing genetic counseling. Diagnosis can be prenatal or postnatal.

Prenatal Diagnosis

1. Ultrasound Screening:
   Signs such as intrauterine growth retardation, heart defects, clenched hands, and abnormal head shape can raise suspicion.
2. Maternal Serum Screening:
   Blood tests measure levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and estriol, which may be abnormal in trisomy cases.
3. Non-Invasive Prenatal Testing (NIPT):
   A blood test from the mother analyzes fetal DNA circulating in maternal blood to detect common trisomies, including Trisomy 18, with high accuracy.
4. Amniocentesis or Chorionic Villus Sampling (CVS):
   These invasive tests collect fetal cells to perform karyotyping—a direct visualization of chromosomes to confirm the presence of extra chromosome 18.

Postnatal Diagnosis

• Based on physical characteristics and symptoms observed at birth.
• Confirmed by karyotype analysis from a blood sample.
• Additional tests like echocardiogram, renal ultrasound, and neurological evaluation to assess associated anomalies.

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Treatment and Management of Trisomy 18 Syndrome

There is no cure for Trisomy 18, as it is a genetic disorder. Treatment focuses on symptom management, supportive care, and improving quality of life.

Medical Management

• Cardiac Care: Monitoring and managing congenital heart defects. Surgery may be considered in select cases based on severity and overall health.
• Feeding Support: Many infants have difficulty feeding due to weak sucking reflex and oromotor problems. Nutritional support may include feeding tubes.
• Respiratory Support: Oxygen therapy or mechanical ventilation for respiratory distress.
• Seizure Management: Anticonvulsants may be used if seizures occur.
• Physical Therapy: To improve muscle tone and mobility.

Supportive Care

• Multidisciplinary team approach involving pediatricians, cardiologists, neurologists, nutritionists, and therapists.
• Focus on comfort care and palliative measures in severe cases.
• Family counseling and psychological support for parents and caregivers.

Ethical Considerations

Given the severity and poor prognosis, families and healthcare providers often face challenging decisions about the extent of medical interventions. Decisions are made case by case, respecting the family’s wishes and quality of life considerations.

Long-Term Outlook

• Survival beyond the first year is rare but possible, especially in mosaic cases.
• Some children may live several years with specialized care.
• Ongoing medical follow-up is essential to manage complications.

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Living with Trisomy 18: Support and Resources

Families affected by Trisomy 18 face emotional and practical challenges. Support groups, genetic counseling, and resources help families cope.

Genetic Counseling

• Important for families planning future pregnancies.
• Helps assess recurrence risk (about 1% for full trisomy, higher for translocation carriers).
• Explains prenatal testing options.

Support Networks

• Organizations like The Trisomy 18 Foundation offer community support and information.
• Online forums connect families worldwide.
• Palliative care teams assist in managing symptoms compassionately.

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Conclusion

Trisomy 18 syndrome is a complex genetic disorder characterized by an extra copy of chromosome 18 that disrupts normal development and causes multiple congenital anomalies. Early detection through prenatal screening and diagnosis is vital for informed decision-making and management planning.

Although there is no cure, comprehensive medical and supportive care can improve comfort and quality of life for affected infants and their families. Awareness, empathy, and genetic counseling play a crucial role in addressing the needs of children with Trisomy 18 and their loved ones.

Frequently Asked Questions (FAQs) About Trisomy 18 Syndrome

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