What is Edwards syndrome?

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 translocation 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 gamete (sperm or oocyte) division resulting in meiotic nondisjunction (failure of a replicating chromosome to divide) is the typical etiology 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 trisomy (affecting all cells) and mosaicism 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 amniotic fluid 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 neural tube 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 less than one month. 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

Carlson, Emily. "Chromosome Miscounts: Understanding Down Syndrome and Other Trisomies." National Institute of General Medical Sciences. National Institutes of Health, 9 Sept. 2013. Web. 21 July 2014.

Crider, Krista S., Richard S. Olney, and Janet D. Cragan. “Trisomies 13 and 18: Population Prevalences, Characteristics, and Prenatal Diagnosis, Metropolitan Atlanta, 1994–2003.” American Journal of Medical Genetics, Part A 146.7 (2008): 820–6. Print.

Houlihan, Orla A., and Keelin O'Donoghue. "The Natural History of Pregnancies with a Diagnosis of Trisomy 18 or Trisomy 13: A Retrospective Case Series." BMC Pregnancy and Childbirth 13.1 (2013): 1–16. Print.

Pont, Stephen J., et al. “Congenital Malformations among Liveborn Infants with Trisomies 18 and 13.” American Journal of Medical Genetics, Part A 140.16 (2006): 1749–56. Print.

"Trisomy 18." MedlinePlus. US Natl. Lib. of Medicine, 8 Sept. 2013. Web. 21 July 2014.

Tucker, Megan E., Holly J. Garringer, and David D. Weaver. “Phenotypic Spectrum of Mosaic Trisomy 18: Two New Patients, a Literature Review, and Counseling Issues.” American Journal of Medical Genetics, Part A 143.5 (2007): 505–17. Print.