(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.
This photo shows prominent heel bones and convex bottoms of the feet.
© Springer Science+Business Media
This photo shows the hand of an infant with trisomy 18. Note the clenched fist and postaxial polydactyly.
Image courtesy of Nina Powell-Hamilton, MD, FAAP, FACMG.
Image courtesy of the Centers for Disease Control and Prevention Public Health Image Library.
Image courtesy of the Centers for Disease Control and Prevention Public Health Image Library.
Image courtesy of the Centers for Disease Control and Prevention Public Health Image Library.
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 analysis on 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 All procedures used to diagnose genetic disorders, except ultrasonography, are invasive and involve slight fetal risk. If testing detects a serious abnormality, the pregnancy can be terminated... read more or chorionic villus sampling Chorionic Villus Sampling All procedures used to diagnose genetic disorders, except ultrasonography, are invasive and involve slight fetal risk. If testing detects a serious abnormality, the pregnancy can be terminated... 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 Practice Bulletins–Obstetrics, Committee of Genetics, and the Society for Maternal–Fetal Medicine 2020 practice bulletin regarding cell-free fetal DNA testing.
Treatment of Trisomy 18
Supportive care
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, but there are now reports of adults with trisomy 18. Children who survive have marked developmental delay and disability, so there is controversy about doing multiple, invasive procedures to correct various associated anomalies. Early referral for physical and speech therapy is important. Support for the family is critical.
Screening for complications
Recently, treatment of some of the associated anomalies has increased survival for certain people 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 ). Because early recognition of these tumors and other anomalies is important for successful treatment (if desired), regular surveillance is recommended. Although the specifics are based mainly on expert opinion at one center, there is a published surveillance protocol for tumors and other complications that many specialists find reasonable (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 
).
If screening detects anomalies, children should be referred to the appropriate specialists.
Surveillance Protocol for Trisomy 18
Time Period | Surveillance Recommendations |
|---|---|
Prenatal | Ultrasonography at 19 weeks gestation Fetal echocardiography considered if known trisomy 18 diagnosis or abnormal ultrasound |
Postnatal | Physical examination for external anomalies Complete blood count with differential Echocardiography Total abdominal ultrasonography, including urinary system (48–72 hours after birth)*,† Cranial ultrasonography and/or MRI Early screening by pediatric ophthalmologist Airway assessment, possibly including sleep study Baseline serum AFP level |
0–12 months of age | Total abdominal ultrasonography at 3, 6, 9, and 12 months of age Serum AFP levels at 3, 6, 9, and 12 months of age Frequent feeding assessments Audiology examination at 6–8 months of age Dental screening |
1–4 years of age | Annual ophthalmologic evaluation After 2 years of age, annual orthopedic examination and spinal x-rays Serum AFP levels every 3–4 months Abdominal ultrasonography every 3 months until 4 years of age Dental evaluation every 6 months |
4–7 years of age | Annual ophthalmologic evaluation Annual orthopedic examination and spinal x-rays Abdominal ultrasonography every 6 months Renal ultrasonography every 3 months until 7 years of age Dental evaluation every 6 months |
7–12 years of age | Annual ophthalmologic evaluation Annual orthopedic examination Abdominal ultrasonography every 6 months until 12 years of age |
Puberty | Clinical evaluation for seizures, behavioral changes, and normal sexual development, including menses in females‡ |
≥ 12 years of age | Annual ophthalmologic evaluation Annual orthopedic examination |
* If prenatal ultrasound showed or suggested hydronephrosis but postnatal ultrasound was normal, renal ultrasonography is done at 4 to 6 weeks of age. | |
† If urinary system abnormalities are present on initial or subsequent ultrasonography, voiding cystourethrography is typically done. | |
‡ Risk of primary or secondary amenorrhea. | |
AFP = alpha-fetoprotein. | |
Adapted from Kepple JW, Fishler KP, Peeples ES: Surveillance guidelines for children with trisomy 18. Am J Med Genet A 185(4):1294–1303, 2021. doi: 10.1002/ajmg.a.62097 | |
Treatment reference
1. Kepple JW, Fishler KP, Peeples ES: Surveillance guidelines for children with trisomy 18. Am J Med Genet A 185(4):1294–1303, 2021. doi: 10.1002/ajmg.a.62097
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.
American College of Obstetricians and Gynecologists Committee on Practice Bulletins–Obstetrics, Committee of Genetics, and the Society for Maternal–Fetal Medicine: Screening for fetal chromosomal abnormalities: ACOG practice bulletin, number 226 (2020)
SOFT (Support Organization for Trisomy 18, 13, and Related Disorders): An organization providing resources, research information, and community and support services to people caring for others who have trisomy 18, 13, or another related chromosome disorder
