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Trisomy 18

(Edwards Syndrome; Trisomy E)

By

Nina N. Powell-Hamilton

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Reviewed/Revised Oct 2023
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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. Prenatal diagnosis is with cytogenetic testing; postnatal diagnosis is with peripheral blood testing. Treatment is supportive.

Trisomy 18 occurs in approximately 4.1/10,000 pregnancies (based on data from induced abortion for fetal anomalies, stillbirths, and live births) (1 General references 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 General references ). More than 95% of affected children have complete trisomy 18 (2 General references 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 General references ). The extra chromosome is almost always maternally derived, and advanced maternal age increases risk. The female:male ratio is 3:1.

General references

Symptoms and Signs of Trisomy 18

Typical findings on prenatal ultrasonography and other fetal testing include polyhydramnios, small placenta, a single umbilical artery, and fetal growth restriction.

Birth weight is low, and there is 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 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.

Common muscular manifestations include hernias, separation of the rectus muscles of the abdominal wall, or both.

Characteristic Physical Features of Trisomy 18

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)

Confirmation prenatally is by cytogenetic testing (karyotyping, FISH analysis, and/or chromosomal microarray analysis ) of samples obtained by amniocentesis Amniocentesis Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... read more or chorionic villus sampling Chorionic Villus Sampling Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... 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.

Diagnosis reference

Treatment of Trisomy 18

  • Supportive care

The underlying genetic abnormality cannot be cured.

Children with trisomy 18 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 of trisomy 18

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 (HCC). 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 Treatment reference ).

If screening detects abnormalities, children should be referred to the appropriate specialists.

Table

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 anomalies 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

Prognosis for Trisomy 18

Prognosis references

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

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