증 례 ISSN 2093-9272일산병원학술지 2018;17(2):106-109

106 Korean Journal of National Health Insurance Service Ilsan Hospital

Introduction

Trisomy 18, also known as Edwards syndrome, is a

chromosomal disorder that occurs due to the presence of

an extra chromosome 18, first described by British physi-

cian John Edwards.1 In population-based studies, the

prevalence of trisomy 18 approximates 1/2000 recog-

nized pregnancies, including abortions, stillbirths, and

live births, and the virtual live birth prevalence ranges

from 1/3600 to 1/10,000.2-4 This difference in prevalence

is explained by the high in-utero lethality of the condition

as well as the intentional termination of many affected

pregnancies. It is not surprising that the survival of living

neonates is likewise bleak. More than half of living neo-

nates die within the first week, and the 1-year survival

rate approximates only 2 %.5,6 The syndrome is three- to

four-fold more common in females.7,8

Virtually every organ system can be affected by trisomy

18. Common major anomalies include heart defects in

more than 90 percent of patients - particularly ventricular

septal defects - as well as cerebellar vermian agenesis,

myelomeningocele, diaphragmatic hernia, omphalocele,

imperforate anus, and renal anomalies such as horseshoe

kidney.7,8

As abnormal fetal heart rate tracings and ‘non-reassur-

ing’ non-stress test results are common during labor in

trisomy 18 deliveries, the mode of delivery and manage-

ment of heart rate abnormalities should be discussed by

에드워드 증후군 초음파와 양수검사로 산전에 진단되고 :

분만 후 확인이 가능한 예

국민건강보험 일산병원 산부인과

한상원 김의혁,

Trisomy 18 that was Prenatally Diagnosed Using Ultrasonography and Fetal Karyotyping, and Visualized Postpartum: Case Report and Literature Review

Sang Won Han, Eui Hyeok Kim

Department of Obstetrics and Gynecology National Health Insurance Service Ilsan Hospital Goyang, Korea

Trisomy 18, also known as Edwards syndrome, occurs in 1 out of 8000 births, and its incidence is much higher among elderly

gravidas. The incidence of trisomy 18 in the living population is not reflective of its true incidence at conception, as 95% of cases

result in spontaneous abortion or stillbirth. It is the second most common autosomal trisomy and causes multiple anomalies,

carrying an extremely poor prognosis. Sonography has been shown to have variable but high sensitivity in detecting trisomy 18

(64%-100%). We report a case of trisomy 18 which was prenatally diagnosed using ultrasonography and fetal karyotyping and

was directly visualized postpartum, with a brief review of the related literature.

Key Words: Trisomy 18 syndromes, Ultrasound imaging, Amniocentesis

책임저자 김의혁: 경기도 고양시 일산동구 일산로 10444 100국민건강보험 일산병원 산부인과

전화 팩스: (031)900-0211, : 0303-3448-7107E-mail : raksumi10@gmail.com

한상원 외 산전에 초음파와 염색체 검사로 확인 된 에드워드 증후군 .

Volume 17 Number 2 December 2018 107

the obstetrician and patient in advance. In older reports,

more than half of undiagnosed fetuses with trisomy 18

underwent cesarean delivery for “fetal distress”.9

Many fetuses with trisomy 18 result in spontaneous

abortion or stillbirth before the second trimester, and so

the living fetus with genetic confirmation of trisomy 18

is rarely observed in utero. We present a case of a fetus

with trisomy 18 who was diagnosed using ultrasound and

genetically confirmed with amniocentesis.

Case

We booked routine antenatal care for a 35-year-old

gravida 2, para 1 woman. She previously underwent cesa-

rean delivery 6 years ago due to breech presentation.

During this pregnancy, she came to the hospital for a

scheduled visit at 18 weeks of gestation. Before the preg-

nancy, she had no medical problems such as hypertension

or diabetes, and the nuchal translucency thickness at 12

weeks of gestation, as measured in high resolution ultra-

sonography, was within the normal range.

She would be 35 years old at delivery-i.e. advanced ma-

ternal age- we decided to undergo amniocentesis without

quadriple test. Before amniocentesis, we did ultrasono-

graphy for fetal inspection at 18 weeks of gestation.

Ultrasound for antenatal care evaluation was routinely

performed at 18 weeks of gestation, and the findings are

outlined below:

Fetal biometry including biparietal diameter, head cir-

cumference, abdominal circumference and femur length,

was appropriate for gestational age. A strawberry-shaped

skull with bilateral choroid plexus cysts in the head,

measuring 1.2 × 0.8 cm (Fig. 1), was noted. Polyhydram-

nios with an amniotic fluid index of 28 and an 8.6 cm

sized deep pocket were also noted (Fig. 2). The stomach of

the fetus was not visualized.

The most prominent finding was multiple anomalies of

the extremities, which included bilateral clenched hands,

clubfoot, limb reduction, radial asplasia, and flexion

deformities. The fetal cardiac axis was severely deviated,

but accurate assessment of the heart was difficult due to

polyhydramnios and an early gestational age for detailed

sonography (Fig. 3).

The fetus was strongly suspected to have Edwards syn-

drome and fetal karyotyping was offered for a definitive

diagnosis, along with appropriate counseling. Amnio-

centesis was performed and Edwards syndrome was con-

firmed by the results of the fetal karyotyping. In view of

the extremely poor prognosis, termination of the preg-

nancy was recommended and was planned with the pa-

Fig 1. Transventricular sonographic view shows fetal

choroid plexus cysts (indicated by arrows) and an angu-

lated “strawberry-shaped” skull.

Fig 2. Measurement of the amniotic fluid index with an

8.6 cm sized deep pocket.

SW Han et al. Trisomy 18 that was Prenatally Diagnosed Using Ultrasonography and Fetal Karyotyping

108 Korean Journal of National Health Insurance Service Ilsan Hospital

tient’s consent. However, in the meantime, intrauterine

fetal death occurred.

The delivery mode was determined to be vaginal birth

although she had previously undergone cesarean delivery.

For induction of labor, misoprostol 400 g (Cytotec, 2 tabµ -

lets) was inserted as a vaginal suppository at an interval of

12 hours.

Approximately 18 hours after induction, a dead fetus

with ambiguous genitalia, weighing 200 grams, was de-

livered vaginally. The directly visualized findings of the

terminated fetus corresponded with the prenatal sono-

graphic findings. Figs 4 and 5 show the gross appearance

after termination. These images show the characteristic

hand position of severe clenched fists and syndactyly

with focal absence of phalanges, as well as clubfoot with

“rocker bottom” appearance. In addition to these find-

ings, micrognathia and malformed, small auricles were

noted (Fig. 6).

The mother was discharged on postpartum day 2 with-

out any complications, including vaginal bleeding.

Discussion

Trisomy 18 is the second most common autosomal

trisomy observed in live births; most cases are detected

in the second trimester.10 As with trisomy 21, also known

as Down syndrome, there is a relationship between ad-

vanced maternal age and the occurrence of trisomy 18 in

offspring due to meiotic nondisjunction. In this case, the

Fig 3. Clubfoot, as demonstrated with the foot in a

fixed, hyperflexed position.

Fig 4. Gross appearance after termination. This image

shows the characteristic hand position of severe.

Fig. 5. Severe clubfoot with “rocker bottom” appearance.

Fig. 6. Micrognathia with small or absent auricles.

한상원 외 산전에 초음파와 염색체 검사로 확인 된 에드워드 증후군 .

Volume 17 Number 2 December 2018 109

patient was 35 years old, which qualifies as advanced

maternal age.

The clinical spectrum of trisomy 18 may involve any

organ system.7,10 The major phenotypic features include

intrauterine growth restriction; hypertonia; strawberry-

shaped calvarium with a pointed front and a flat occiput;

small mouth; micrognathia; small malformed ears; short

sternum; horseshoe kidney; and flexed fingers, with the

index finger overlapping the third finger and the fifth

finger overlapping the fourth. Congenital heart disease

occurs in greater than 50 percent of affected offspring,

with valvular heart disease being common. However,

ventricular septal defects and patent duct arteriosus are

the most common defects. The gastrointestinal system is

involved in approximately 75 percent of cases; Meckel’s

diverticulum and malrotation are the predominant ab-

normalities. Omphalocele is relatively common in tris-

omy 18. The frequency of sonographically-detected gross

anomalies in fetuses with trisomy 18 varies with gesta-

tional age, and is approximately 53 percent up to and in-

cluding 17.5 weeks of gestation, and 67 percent from

17.5 to 24 weeks.11

The prognosis of trisomy 18 is very poor even in live-

birth though most fetuses were aborted and international

consensus on guidelines for care that includes all of the

specialties involved in the care of fetuses, newborn, and

older children with trisomy 18 is required. And avoid-

ance of the termination at term due to late diagnosis is

essential for easy procedure.

We have herein reported a case of trisomy 18, prenatally

diagnosed using ultrasonography and fetal karyotyping

and then directly visualized at postpartum, with a brief

review of the related literature.

REFERENCES

1. Edwards JH, Harnden DG, Cameron AH, Crosse VM, Wolf OH. A new trisomic syndrome. Lancet 1960;275: 787-90.

2. Loane M, Morris JK, Addor M, Arriola L, Budd J, Doray B, et al. Twenty-year trends in the prevalence of down syndrome and other trisomies in europe: Impact of ma-ternal age and prenatal screening. Eur J Hum Genet 2013; 21:27-33.

3. Root S, Carey JC. Survival in trisomy 18. Am J Med Genet 1994;49:170-4.

4. Rasmussen SA, Wong LC, Yang Q, May KM, Friedman JM. Population-based analyses of mortality in trisomy 13 and trisomy 18. Pediatrics 2003;111:777.

5. Vendola C, Canfield M, Daiger SP, Gambello M, Hashmi SS, King T, et al. Survival of Texas infants born with tri-somies 21, 18, and 13. Am J Med Genet A 2010;152A: 360-6.

6. Tennant PW, Pearce MS, Bythell M, Rankin J. 20-year survival of children born with congenital anomalies: A population-based study. Lancet. 2010;375:649-56.

7. Lin H, Lin S, Chen Y, Hung H, Kao H, Hsu C, et al. Clinical characteristics and survival of trisomy 18 in a medical center in Taipei, 1988 2004. Am J Med Genet –A 2006;140A:945-51.

8. Rosa RFM, Rosa RCM, Lorenzen MB, de Moraes FN, Graziadio C, Zen PRG, et al. Trisomy 18: Experience of a reference hospital from the south of brazil. Am J Med Genet A. 2011;155:1529-35.

9. Schneider AS, Mennuti MT, Zackai EH. High cesarean section rate in trisomy 18 births: A potential indication for late prenatal diagnosis. Am J Obstet Gynecol 1981; 140:367.

10. Jones KL, Smith DW. Smith’s recognizable patterns of human malformation. 6. ed. Philadelphia, PA: Elsevier Saunders; 2006.

11. Bahado-Singh RO, Choi S, Oz U, Mendilcioglu I, Rowther M, Persutte W. Early second-trimester individualized estimation of trisomy 18 risk by ultrasound. Obstet Gynecol 2003;101:463-8.