Trisomy 18
Introduction to Trisomy 18
Trisomy 18, also known as Edwards syndrome, is a chromosomal disorder characterized by the presence of an extra chromosome 18. It is the second most common autosomal trisomy after Down syndrome, occurring in approximately 1 in 6,000 to 8,000 live births.
Key points:
- First described by John Hilton Edwards in 1960
- Associated with severe intellectual disability and multiple physical abnormalities
- Most affected individuals do not survive beyond the first year of life
- More common in female infants
- Risk increases with maternal age
Genetics of Trisomy 18
Trisomy 18 is caused by the presence of an extra copy of chromosome 18. There are three types of Trisomy 18:
- Full Trisomy 18: Accounts for about 95% of cases. All cells have three copies of chromosome 18.
- Mosaic Trisomy 18: Accounts for about 5% of cases. Only some cells have the extra chromosome 18.
- Partial Trisomy 18: Rare. Only a portion of the extra chromosome 18 is present.
Risk factors for Trisomy 18 include:
- Advanced maternal age (risk increases after age 35)
- Previous pregnancy with a chromosomal abnormality
- Parental balanced translocation involving chromosome 18
Clinical Features of Trisomy 18
Trisomy 18 is characterized by a wide range of physical and developmental abnormalities. Common features include:
Physical Characteristics:
- Low birth weight and poor growth
- Small, abnormally shaped head (microcephaly)
- Prominent occiput
- Low-set and malformed ears
- Small mouth and jaw (micrognathia)
- Clenched fists with overlapping fingers
- Rocker-bottom feet
- Short sternum
- Umbilical or inguinal hernia
- Underdeveloped fingernails and toenails
Developmental Characteristics:
- Severe intellectual disability
- Significant developmental delays
- Feeding difficulties
- Limited responsiveness to stimuli
Diagnosis of Trisomy 18
Trisomy 18 can be diagnosed prenatally or after birth. Diagnostic methods include:
Prenatal Screening and Diagnosis:
- Non-invasive prenatal testing (NIPT): Cell-free fetal DNA analysis
- First-trimester combined test: Nuchal translucency ultrasound and maternal blood tests
- Quad screen: Second-trimester maternal blood test
- Ultrasound findings: May show characteristic abnormalities
- Diagnostic tests:
- Chorionic villus sampling (CVS): 10-13 weeks gestation
- Amniocentesis: After 15 weeks gestation
Postnatal Diagnosis:
- Physical examination: Characteristic features may be apparent at birth
- Chromosomal karyotype: Confirms diagnosis and determines type of Trisomy 18
Associated Conditions in Trisomy 18
Individuals with Trisomy 18 often have multiple congenital anomalies affecting various organ systems:
- Cardiovascular defects (>90% of cases)
- Ventricular septal defect
- Atrial septal defect
- Patent ductus arteriosus
- Coarctation of the aorta
- Central nervous system abnormalities
- Dandy-Walker malformation
- Corpus callosum agenesis
- Holoprosencephaly
- Gastrointestinal issues
- Omphalocele
- Esophageal atresia
- Tracheoesophageal fistula
- Genitourinary abnormalities
- Horseshoe kidney
- Hydronephrosis
- Cryptorchidism in males
- Respiratory problems
- Pulmonary hypoplasia
- Diaphragmatic hernia
- Skeletal anomalies
- Scoliosis
- Rib abnormalities
Management of Trisomy 18
Management of Trisomy 18 is primarily supportive and palliative, focusing on the individual's quality of life. The approach includes:
Medical Management:
- Intensive care support for severe cases
- Management of respiratory difficulties
- Feeding support (nasogastric tube or gastrostomy)
- Treatment of infections
- Pain management
- Cardiac care for associated heart defects
Surgical Interventions:
- Decisions regarding surgery are complex and individualized
- May include repair of life-threatening defects in selected cases
- Ethical considerations play a significant role in decision-making
Supportive Care:
- Physical therapy
- Occupational therapy
- Speech and language therapy
- Nutritional support
Family Support:
- Genetic counseling
- Psychological support
- Palliative care consultation
- Support groups and resources
Prognosis in Trisomy 18
The prognosis for individuals with Trisomy 18 is generally poor:
- Approximately 50% of infants with Trisomy 18 survive beyond the first week of life
- About 5-10% of infants survive beyond the first year
- Median survival for live births is 10-14 days
- Survival rates are higher for females compared to males
- Individuals with mosaic Trisomy 18 may have a better prognosis
Factors affecting prognosis include:
- Severity of congenital anomalies
- Presence of major cardiac defects
- Degree of medical intervention provided
- Type of Trisomy 18 (full, mosaic, or partial)
Long-term survivors face significant medical challenges and developmental delays. However, some individuals with Trisomy 18 have survived into adulthood with appropriate medical care and support.
Trisomy 18
- What is the genetic cause of Trisomy 18?
An extra copy of chromosome 18, resulting in 47 chromosomes instead of the typical 46. - What is another name for Trisomy 18?
Edwards syndrome - What is the approximate incidence of Trisomy 18?
About 1 in 6,000-8,000 live births - Which gender is more commonly affected by Trisomy 18?
Females (ratio of approximately 3:1 female to male) - What percentage of Trisomy 18 cases are caused by meiotic nondisjunction?
Approximately 95% of cases - Which cardiac defect is most commonly associated with Trisomy 18?
Ventricular septal defect (VSD) - What is a characteristic hand position often observed in infants with Trisomy 18?
Clenched fists with overlapping fingers - Which skull shape abnormality is frequently seen in Trisomy 18?
Strawberry-shaped skull (prominent occiput) - What is the typical life expectancy for infants born with Trisomy 18?
Most infants do not survive beyond the first year of life, with median survival of 10-14 days - Which prenatal screening test can indicate an increased risk for Trisomy 18?
Quad screen (second-trimester maternal serum screening) - What is the recurrence risk for parents who have had a child with Trisomy 18?
Approximately 1% for future pregnancies - Which renal abnormality is commonly associated with Trisomy 18?
Horseshoe kidney - What is the characteristic appearance of the feet in Trisomy 18?
Rocker-bottom feet - Which non-invasive prenatal test can screen for Trisomy 18?
Cell-free fetal DNA testing - What percentage of Trisomy 18 cases are due to mosaic Trisomy 18?
About 5% of cases - Which growth parameter is typically affected in fetuses with Trisomy 18?
Intrauterine growth restriction (IUGR) - What is the typical karyotype notation for Trisomy 18?
47,XX,+18 or 47,XY,+18 - Which gastrointestinal abnormality is frequently associated with Trisomy 18?
Omphalocele (abdominal wall defect) - What percentage of fetuses with Trisomy 18 are thought to be lost before birth?
Approximately 95% of conceptuses - Which facial feature is often observed in infants with Trisomy 18?
Micrognathia (small jaw) - What is the approximate percentage of Trisomy 18 cases that are due to translocation?
About 5% of cases - Which neurological finding is commonly present in infants with Trisomy 18?
Microcephaly (abnormally small head) - What is the recommended management approach for infants with Trisomy 18?
Supportive care and palliative measures, with treatment decisions based on individual circumstances and family preferences - Which chromosomal region is most commonly involved in translocations causing Trisomy 18?
The long arm of chromosome 18 and another acrocentric chromosome - What is the typical presentation of the ears in Trisomy 18?
Low-set and malformed ears - Which endocrine abnormality is sometimes observed in Trisomy 18?
Thyroid dysgenesis - What is the most common cause of death in infants with Trisomy 18?
Cardiopulmonary failure - Which pulmonary condition is often associated with Trisomy 18?
Pulmonary hypoplasia - What is the typical appearance of the sternum in infants with Trisomy 18?
Short sternum - Which molecular technique can be used to confirm Trisomy 18 in tissue samples?
Fluorescence in situ hybridization (FISH)
