(Edwards Syndrome; Trisomy E)
Trisomy 18 is caused by an extra chromosome 18 and is usually associated with intellectual disability, small birth size, and various congenital anomalies, including severe microcephaly, heart defects, prominent occiput, low-set malformed ears, and a characteristic pinched facial appearance.
Trisomy 18 occurs in 1/6000 live births, but spontaneous abortions are common. More than 95% of affected children have complete trisomy 18. The extra chromosome is almost always maternally derived, and advanced maternal age increases risk. The female:male ratio is 3:1.
A prenatal history of feeble fetal activity, polyhydramnios, a small placenta, and a single umbilical artery often exist. Size at birth is markedly small for gestational age, with hypotonia and marked hypoplasia of skeletal muscle and subcutaneous fat. The cry is weak, and response to sound is decreased. The orbital ridges are hypoplastic, the palpebral fissures are short, and the mouth and jaw are small; all of these characteristics give the face a pinched appearance. Microcephaly, prominent occiput, low-set malformed ears, narrow pelvis, and a short sternum are common.
A clenched fist with the index finger overlapping the 3rd and 4th fingers usually occurs. The distal crease on the 5th finger is often absent, and there is a low-arch dermal ridge pattern on the fingertips. Redundant skinfolds, especially over the back of the neck, are common. The fingernails are hypoplastic, and the big toe is shortened and frequently dorsiflexed. Clubfeet and rocker-bottom feet are common. Severe congenital heart disease is common, especially patent ductus arteriosus and ventricular septal defects. Anomalies of lungs, diaphragm, GI tract, abdominal wall, kidneys, and ureters are frequent. Boys may have undescended testes. Common muscular manifestations include hernias, separation of the rectus muscles of the abdominal wall, or both.
Diagnosis of trisomy 18 may be suspected postnatally by appearance, or prenatally on ultrasonography (eg, with abnormalities of extremities and fetal growth restriction), or by multiple marker screening or noninvasive prenatal screening (NIPS) using cell-free fetal DNA sequences obtained from a maternal blood sample.
Confirmation in all cases is by cytogenetic testing (karyotyping, fluorescent in situ hybridization [FISH] analysis, and/or chromosomal microarray analysis [CMA]) of samples obtained by amniocentesis or chorionic villus sampling. Trisomy 18 detected on chorionic villus sampling may warrant further investigation either by amniocentesis or postnatal testing because the trisomy may represent confined placental mosaicism, in which aneuploidy is present in the placenta but undetectable in the fetus.
Confirmatory testing also is done in cases suspected based on NIPS, particularly when the screening result is indeterminate or unclear; in younger women, in whom the positive predictive value of NIPS is lower; and to diagnose other fetal chromosomal disorders. Management decisions, including termination of pregnancy, should not be made based on NIPS testing alone. See also The American College of Obstetricians and Gynecologists Committee on Genetics and the Society for Maternal–Fetal Medicine committee opinionregarding cell-free fetal DNA testing.