Edwards syndrome
Edwards syndrome, also known as Trisomy 18, is a severe congenital genetic condition caused by the presence of an extra chromosome 18. This anomaly occurs in approximately 1 in 3,000 to 5,000 pregnancies and is often associated with significant complications, leading to spontaneous abortion, intrauterine death, or elective termination in about 95% of cases. For the small percentage of infants who survive to birth, the prognosis is poor, with a 90-95% mortality rate within the first year of life.
Key indicators of Edwards syndrome include a range of physical anomalies such as growth retardation, skeletal deformities, and cardiac defects, which can often be detected through prenatal ultrasounds. There is no known prevention for the syndrome, and risk factors include advanced maternal and paternal age. Although the condition affects individuals regardless of racial or ethnic background, more female fetuses are born with Edwards syndrome due to higher male fetal mortality rates.
While there is no cure, supportive care focusing on comfort is typically provided for affected infants, with varying degrees of developmental and cognitive outcomes. Understanding the syndrome helps in early detection and informed decision-making for families facing this diagnosis.
Edwards syndrome
ALSO KNOWN AS: Trisomy 18; complete trisomy 18
DEFINITION Edwards syndrome is a congenital genetic aneuploidic (abnormal number of chromosomes) abnormality arising when a fetus has an extra number 18 autosomal chromosome. The syndrome was initially described by John H. Edwards and associates in 1960. It occurs in 1 in 3,000 to 5,000 pregnancies and ends in spontaneous abortion, intrauterine death, or elective termination in approximately 95 percent of cases. In the 5 percent of affected fetuses surviving to term, multiple anomalies occur. The mortality rate of live-born infants within the first year of life is 90 to 95 percent. In 2024, researchers found evidence of a perinate or infant with trisomy 18 in a burial site in Iron Age Spain, indicating that people living as long as 2,800 years ago experienced this genetic condition.
Risk Factors
Edwards syndrome can occur at any maternal age but occurs more frequently with advanced maternal age (more than thirty-five years). In addition, slightly more than 50 percent of infants with Edwards syndrome have a paternal age greater than forty years. There is no racial or ethnic predilection to the syndrome. The in utero female-to-male ratio is 1 to 1. However, more male fetuses die in utero or are spontaneously aborted and thus live births are approximately 80 percent female. Individuals with a of chromosome 18 material are at a 50 percent risk of transmitting the complete syndrome (all cells affected) to their progeny.
Etiology and Genetics
An error in (sperm or oocyte) division resulting in meiotic nondisjunction (failure of a replicating chromosome to divide) is the typical of Edwards syndrome. In 95 percent of cases, the somatic cells contain three copies of chromosome 18 rather than the normal two. This extra genetic material is responsible for the multiple anomalies and developmental and cognitive deficits present with this syndrome. The remaining 5 percent of cases exhibit mosaicism (trisomy in some but not all cells) or translocation (extra chromosome 18 genetic material is attached to a normal chromosome). In some infants with mosiacism or translocation, associated anomalies may be less and the individual may phenotypically appear unaffected. Developmental and cognitive function varies from severe to normal in these individuals. Complete (affecting all cells) and are not inherited but result from a de novo (new) mutation. Translocation trisomic individuals have a 50 percent chance of each offspring inheriting complete trisomy 18.
Symptoms
Prenatally, intrauterine growth deficiency accompanied by polyhydramnios (a large volume of due to defective fetal swallowing) is common. Anomalies may be detected by fetal ultrasound.
Postnatally, the affected infant presents with classic signs and symptoms. They include central nervous system malformations (microcephaly with a prominent occiput, hydrocephaly, and defects); cardiac defects (ventricular and atrial septal defects, coarctation of the aorta); skeletal anomalies (growth retardation, clenched fist with index finger overlapping the middle finger and fifth finger overlapping the fourth, rocker bottom feet); gastrointestinal defects (omphalocele, malrotation); head and face issues (microphthalmia, micrognathia, microstomia, and low-set, malformed ears); and genitourinary obstruction. Feeding difficulties, developmental delay, and mental retardation are almost always present.
Screening and Diagnosis
Screening for aneuploidy can be done during the first trimester of the pregnancy from weeks ten to fourteen. The evaluation includes maternal age, fetal nuchal translucency, fetal heart rate, maternal serum free beta human chorionic gonadotrophin (beta-hCG), and maternal serum pregnancy-associated plasma protein-A (PAPP-A). These factors are successful in predicting approximately 90 percent of affected fetuses with a 3-percent false positive rate. Positive screening is then followed by definitive prenatal testing, including the analysis of fetal cells obtained by either chorionic villus sampling or amniocentesis.
When prenatal screening is not performed, infants are diagnosed after delivery as a result of common prevalent features and anomalies and clinical instability. Cytogenetic testing confirms the diagnosis.
Treatment and Therapy
The diagnosis of Edwards syndrome requires thoughtful clinical decision-making. Because of the high mortality rate of this syndrome and inability to offer a cure, comfort measures only may be offered to the infant. In surviving infants, appropriate health care services are offered depending on the types of anomalies and degree of developmental delay and mental retardation present.
Prevention and Outcomes
Currently, there are no known preventive strategies. The spontaneous prenatal death rate is high. With prenatal diagnosis, elective termination of the pregnancy is often performed.
For live-born infants, the prognosis is grim, with the median survival of live-born complete trisomic cases being fourteen days. Between 90 and 95 percent die within the first year of life. Survival up to the third decade of life has been reported. Some affected individuals are institutionalized and others are cared for in the home.
Care providers should be alert to abnormal fetal growth patterns. Prenatal ultrasound and laboratory testing can be offered. After birth, all infants require a thorough physical examination and follow-up of any abnormalities.
Bibliography
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Rohrlach, A.B., Rivollat, M., de-Miguel-Ibáñez, P. et al. "Cases of Trisomy 21 and Trisomy 18 among Historic and Prehistoric Individuals Discovered from Ancient DNA. Nature Communications, 20 Feb. 2024, 15, 1294, doi.org/10.1038/s41467-024-45438-1. Accessed 3 Sept. 2024.
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