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1992-08-09-14 Trisomy 18 © Izquierdo

Trisomy 18

Luis A. Izquierdo, MD, Maggie Vill, MD, Debra Jones, MD, Teresa Castellano, MS, Marshall Levine, MD, Gloria E. Sarto, MD, PhD 

Address correspondence to Luis A. Izquierdo, MD, University of New Mexico School of Medicine, Department of Ob/Gyn, Division of Maternal-Fetal Medicine, 2211 Lomas Blvd., NE, Albuquerque, New Mexico 87131-5286 Ph: 505-277-8381 Fax: 505-272-6385

Synonyms: Edwards syndrome, trisomy E.

Definition:  Multiple malformation syndrome with a trisomy for all or a large part of the number 18 chromosome.

Prevalence: 3:10,000 live births with a maternal age effect.

Etiology: Parental non-disjunction, rarely parental translocation. About 80% percent of the patients have a straight trisomy, another 10% are mosaics, whereas the rest either are double trisomics for another chromosome or have a translocation. Pericentric inversion in chromosome 18 has been described to recombine during meiosis and cause unbalanced offspring pheno­tipically similar to those fetuses with trisomy 181,2 

Pathogenesis:  Results from a faulty chromosomal distribution, which is most likely to occur in the older gravida age. Increased maternal age is a risk factor, and the parental origin of the extra chromosome is maternal in 96% of cases in whom chromosomal origin could be determined3.

Associated anomalies:  Congenital heart disease, growth retardation, polyhydramnios, prominent occiput, micrognathia, clenched hand, short sternum.

Differential diagnosis:  Multiple malformation syndromes which include severe growth retardation, polyhydramnios, and congenital heart disease such as trisomy 13 and triploidy. Pena-Shokeir syndrome should also be included in the differential diagnosis4.

Prognosis:  Although trisomy 18 is less common than trisomy 21, it is more lethal. Ninety-six percent of live-born trisomy 18 infants die in the first year of life. Thirty percent die within the first month of life, 50% within two months, and only 10% survive the first year and are profoundly mentally retarded3,5,6. Approximately 68% of the fetuses with an in utero diagnosis of trisomy 18 die before delivery3.

Recurrence risk:  For full trisomy 18, the recurrence risk is lower than the 1% for full trisomy 21 syndrome. A carrier of pericentric inversion in chromosome 18 may produce affected offspring in 6% of pregnancies and carrier offspring in 53% of such pregnancies1,2.

Management:  When ultrasound findings are consistent with trisomy 18, prenatal karyotying should be undertaken. Pregnancy termination should be considered. Tocolysis for preterm labor and cesarean section should be avoided.

MESH Trisomy 18 BDE 0160 MIM 257300 POS 3094 ICD9 758.2 CDC 758.000


Trisomy 18, after trisomy 21, is the second most common multiple malformation syndrome. It has an incidence of about 3:10,000 newborn infants5. The incidence at conception is much higher, but 95% of the affected fetuses abort spontaneously7.

Multiple different abnormalities have been reported in the literature as features of fetuses and newborns with trisomy 18 syndrome. These include low birth weight, multiple dysmorphic features, prominent occiput, clench­ed hands, rocker-bottom feet, and a short sternum. Malformations of the heart, kidneys, and other organs are also frequent. The autopsy findings in 31 neonates and stillborns with trisomy 18 were reported by Kalousek et al.

Several authors have described the use of ultrasound for evaluation of structural malformations and growth retardation observed in chromosomally abnormal newborns6,9-19. A case of trisomy 18 and review of the literature regarding this syndrome are presented.

Case report

A 29-year-old woman G2P1 at 34 weeks estimated gestational age, was referred to the obstetrical ultrasound unit for a second opinion ultrasound because of a suspected brain anomaly and growth retardation. Our evaluation showed the following findings: the brain presented evidence of mild atrial enlargement of 14 mm, the cavum was intact, the posterior fossa showed a hypoplastic cerebellum (transverse cerebellar diameter: 23 mm) with an intact vermis, and an enlarged cisterna magna of 26 mm (fig. 1,2).

Figure 1: Midsagittal view of the brain showing an enlarged cisterna magna and hypoplastic cerebellum.


 Figure 2: Axial views of the posterior fossa showing an enlarged cisterna with a normal vermis. 

The heart had a normal four-chamber view, but a perimembranous ventricular septal defect and an overriding aorta (fig. 3) with a normal pulmonary outflow tract suggested a double outlet right ventricle. The abdominal anatomy was normal. The cord contained three vessels. The hands were clenched with an overlapping index and fifth finger (fig. 4). Growth charts assigned this fetus to a weight below the 5% percentile.

Figure 3: The great vessel is overriding the interventricular septum.

Figure 4: Clenched hand. Overlapping of the third finger by the index (blue arrow), and of the fourth finger by the fifth (yellow arrow).

The patient was counseled that the fetus had a high probability of having trisomy 18. Cordocentesis confirmed that the karyotype was 47 XX, +18. The patient decided to have no intervention for the delivery of this fetus. A female fetus was delivered at 40 weeks of gestation weighing 1840g, Apgars 7 and 9 at 1 and 5 min, respectively. Evaluation by a pediatric dysmorphologist confirmed the antenately described findings (fig. 5). After discussion between the neonatal group and the infant"s family, the newborn was discharged home with an alert of possible feeding problems. At the time of writing of this manuscript, this newborn is two weeks old.

Figure 5: The newborn: note the dysmorphic features of trisomy 18.


We present a case of a trisomy 18 in which neither maternal serum aFP screening nor mid-trimester ultrasound was performed. This young patient was referred for a second opinion ultrasound because of suspected fetal anomalies. This fetus had a multiple malformation syndrome that was consistent with the classical features of trisomy 18. The diagnosis was proven by prenatal karyotyping.


Trisomy 18 is also known as Edwards" syndrome. Prior to banding and staining techniques, the extra chromosome 18 belonged to the Group E, reporting this syndrome as trisomy E.


Edwards" syndrome is a multiple malformation syndrome with a trisomy for all or a large part of the number 18 chromosome.


The incidence of this autosomal trisomy is about 3:10,000 livebirths.


Most commonly, trisomy 18 is due to parental non-disjunction. Only rarely, it may be due to parental translocations. About 80% of the patients have a straight trisomy, another 10% are mosaics, and the remainder either are double trisomics for another chromosome or have a translocation. Pericentric inversion in chromosome 18 has been described to cause unbalanced offspring by recombination during meiosis that is phenotipically similar to full trisomy 181,2.


Most commonly, trisomy 18 results from a faulty chromosomal distribution, which is most likely to occur in the older gravida. The parental origin of the extra chromosome is maternal in 96% of the cases in whom chromosomal origin could be determined3.

Associated anomalies

Growth retardation, multiple congenital anomalies, and early death are constant features of trisomy 18. The autopsy findings of 31 neonates and stillborns with trisomy 18 are presented in Table 13.

Table 1: Associated anomalies in trisomy 18 (reproduced with permission from Dimmick & Kalousek3). The first column of numbers represents the number of cases; the second, the percentage of cases affected.

External features


g Growth retardation        27            87

g Thin body habitus         4              13

g Short sternum                 4              13

g Hydrops                          3              10

g Small pelvis                     2              6

g Cystic hygroma              1              3

g Redundant skin              1             3

g Abnormal ribs                3             10

g Hemivertebrae                1             3

g Cystic hygroma             1              3

g Redundant skin              1              3

g Abnormal ribs                3              10

g Hemivertebrae                1              3

Face and head

g Low-set ears                   18            58

g Recessed chin                                15            48

g Small face                        11            35

g Abnormal ears                11            35

g Small eyes                       8             26

g Small mouth                    5             16

g Microcephaly                 5             16

g Large anterior

     fontanelle                      4                13

g Hypertelorism                 2             6

g Choanal atresia              2              6

g Preauricular tag              2              6

g High-arched palate        2             6

g Corneal opacification    1             3

g Cleft palate                      1             3

g Small anterior

     fontanelle                        1              3

g Third fontanelle             1             3

g Low hair line                   1             3


g Overlapping fingers      22            71

g Rockerbottom feet         12            39

g Clubfeet                           10            32

g Single palmar crease      7             23

g Hypoplastic nails           6             19

g Clinodactyly                   4             13

g Syndactyly                     3             10

g Hip dislocation               2             6

g Ulnar deviation of

     hands                               2             6

g Cleft in hand                   1             3

g Small great toe                1             3


Internal features

Cardiovascular system

g Ventricular septal

     defect                               25            81

g Polyvalvular dysplasia 20            65

g Bicuspid aortic valve    14            45

g Bicuspid pulmonary

     valve                                13            42

g Coarctation of the

     aorta                                 11            35

g Left superior

     vena cava                         6             19

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