(See also Overview of Chromosomal Anomalies Overview of Chromosomal Anomalies Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more .)
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 of Trisomy 18
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 Microcephaly Microcephaly is a head circumference 2 standard deviations below the mean for age. (See also Introduction to Congenital Craniofacial and Musculoskeletal Disorders and Overview of Congenital... read more , 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 Patent Ductus Arteriosus (PDA) Patent ductus arteriosus (PDA) is a persistence of the fetal connection (ductus arteriosus) between the aorta and pulmonary artery after birth. In the absence of other structural heart abnormalities... read more and ventricular septal defects Ventricular Septal Defect (VSD) A ventricular septal defect (VSD) is an opening in the interventricular septum, causing a shunt between ventricles. Large defects result in a significant left-to-right shunt and cause dyspnea... read more . Anomalies of lungs, diaphragm, gastrointestinal tract, abdominal wall, kidneys, and ureters are frequent. Boys may have undescended testes Cryptorchidism Cryptorchidism is failure of one or both testes to descend into the scrotum; in younger children, it is typically accompanied by inguinal hernia. Diagnosis is by testicular examination, sometimes... read more . Common muscular manifestations include hernias, separation of the rectus muscles of the abdominal wall, or both.
Diagnosis of Trisomy 18
Prenatal chorionic villus sampling and/or amniocentesis with cytogenetic testing by karyotype analysis, fluorescent in situ hybridization (FISH), and/or chromosomal microarray analysis (CMA)
(See also Next-generation sequencing technologies Genetic Diagnostic Technologies Genetic diagnostic technology is rapidly improving. A small amount of DNA can be amplified using the polymerase chain reaction (PCR) process, which can produce millions of copies of a gene or... read more .)
Diagnosis of trisomy 18 may be suspected postnatally by appearance, or prenatally on ultrasonography Screening Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more (eg, with abnormalities of extremities and fetal growth restriction), or by multiple marker screening or noninvasive prenatal screening Screening Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more (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 Amniocentesis Genetic evaluation is part of routine prenatal care and is ideally done before conception. The extent of genetic evaluation a woman chooses is related to how the woman weighs factors such as... read more or chorionic villus sampling Chorionic Villus Sampling Genetic evaluation is part of routine prenatal care and is ideally done before conception. The extent of genetic evaluation a woman chooses is related to how the woman weighs factors such as... read more , 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 of Trisomy 18
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 Hepatoblastoma Primary liver cancer is usually hepatocellular carcinoma. The first manifestations of liver cancer are usually nonspecific, delaying the diagnosis. When diagnosed at advanced stages, prognosis... read more , Wilms tumor Diagnosis Wilms tumor is an embryonal cancer of the kidney composed of blastemal, stromal, and epithelial elements. Genetic abnormalities have been implicated in the pathogenesis, but familial inheritance... read more ). Tumor surveillance is recommended. Although the specifics are controversial, the following protocol has been proposed (1 Treatment reference 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... read more ):
Alpha fetoprotein (AFP) level at baseline and every 3 months until age 4 years (for hepatoblastoma)
Abdominal ultrasonography every 3 months until age 4 years (for hepatoblastoma and Wilms tumor)
Renal ultrasonography every 3 months from age 4 years to at least age 7 (for Wilms tumor)
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.
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