(See also Overview of Chromosomal Anomalies.)
Trisomy 18 occurs in 1/6000 live births, but spontaneous pregnancy losses 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.
Symptoms and Signs
A prenatal history of feeble fetal activity, polyhydramnios, a small placenta, and a single umbilical artery often exist. Size prenatally and 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 often occurs. The distal crease on the 5th finger is often absent. 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, gastrointestinal 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.
This photo shows prominent heel bones and convex bottoms of the feet.
This photo shows the feet of an infant with trisomy 18. Note the rocker-bottom feet with prominent calcanei.
This photo shows the hand of an infant with trisomy 18. Note the clenched fist and postaxial polydactyly.
Diagnosis
(See also Next-generation sequencing technologies.)
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. The sensitivity and specificity of NIPS for trisomy 18 is relatively low, compared to trisomy 21.
Confirmation prenatally is by cytogenetic testing (karyotyping, FISH analysis, and/or chromosomal microarray analysis ) of samples obtained by amniocentesis or chorionic villus sampling, or postnatally by testing peripheral blood for women who did not wish to have additional procedures during pregnancy. 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 practice bulletin regarding cell-free fetal DNA testing.
Treatment
No specific trisomy 18 treatment is available. More than 50% of children die within the first week; only 5 to 10% survive the first year. Children who survive have marked developmental delay and disability. Support for the family is critical.
Recently, survival has increased for children with trisomy 18, which has led to recognition of an increased risk of solid organ tumors (eg, hepatoblastoma, Wilms tumor). Tumor surveillance is recommended. Although the specifics are controversial, the following protocol has been proposed (1):
Treatment reference
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1. Farmakis SG, Barnes AM, Carey JC, Braddock SR: Solid tumor screening recommendations in trisomy 18. Am J Med Genet A 179(3):455–466, 2019. doi: 10.1002/ajmg.a.61029.
More Information
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
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American College of Obstetricians and Gynecologists Committee on Genetics and the Society for Maternal-Fetal Medicine Publications Committee: Practice bulletin on screening for fetal aneuploidy
