Trisomy 18 is a serious chromosomal anomaly which has a very poor (usually lethal) prognosis. T18 is usually associated with a variety of sonographically detectable abnormalities.
Trisomy 18 is a serious chromosomal anomaly which has a very poor (usually lethal) prognosis. T18 is usually associated with a variety of sonographically detectable abnormalities. We report a case of T18 in association with cystic adenomatoid malformation(CAM) of the lung. This case is interesting because the CAM was initially the only detected abnormality. It was only on the subsequent detailed anatomy scan that other anomalies were uncovered which indicated the presence of T18. These findings prompted invasive diagnostic testing in the form of fetal umbilical blood sampling, which confirmed T18 karyotype.
Trisomy 18 (T18) is the name given to group of individuals who carry an extra 18th chromosome. There can be varying degrees of mosaicism and translocation, but these are infrequently seen. Trisomy 18 is found one in every 3000 pregnancies with a male to female ratio of 1:3. The poor prognosis of this disorder is reflected in the mortality rates. Of the pregnancies affected, 50 % will die within two months and 90% will not survive the first year. Uterine demise and stillbirth often occur. There are no known teratogens although maternal age and family history of chromosomal disorders are known risks.
A variety of sonographic findings have been reported in association with T18. The most common anatomic defects include: cardiac abnormalities, choroid plexus cysts, omphalocele (usually containing small bowel ), gastrointestinal abnormalities, and limb abnormalities (clenched hands, and talipes). Early onset symmetrical IUGR, and polyhydramnios are also frequently noted.
Sonographic Findings Associated with T18:
|CRANIOFACIAL||CENTRAL NERVOUS SYSTEM||CARDIOVASCULAR|
|Cleft Lip/Palate||Choroid Plexus Cysts||Ventricular Septal Defect (VSD)|
|Microcephaly||Absent Corpus Callosum||Atrial Septal Defect (ASD)|
|Micrognathia||Hydrocephalus||Double Outlet Ventricle|
|Dolicocephaly||Prominent Cisterna Magna||Bicuspid Outflow Tract Valves|
|Cerebellar Hypoplasia||Single Umbilical Artery|
|Esophageal Atresia||Renal Dysplasia||Clenched Hands- Arthrogryposis|
|Tracheo-Esophageal Fistula||Horseshoe Kidney||Overlapping Digits|
|Omphalocele||Ureterovesical Obstruction||Rockerbottom Feet|
|Diaphragmatic Hernia||Short Extremities|
Cystic Adenomatoid Lung Malformation
Cystic Adenomatoid Malformation (CAM) is a benign hamartomatous lung mass. Although the lesion itself is benign, CAM may lead to adverse outcome if: 1) the lesion is large and causes compression of the thoracic contents, 2) hydrops develops secondary to the CAM, or 3) other associated anomalies are present. Three distinct subcategories have been described based on the ultrasound appearances.
Types of Cystic Adenomatoid Malformations:
|I||Macrocystic||Usually large solitary cyst or several cysts are present.||Good prognosis with resection.|
|II||Polymicrocystic / Mixed||Multiple small cysts are present (<1cm) with surrounding echogenic components||May be associated with other anomalies.|
|III||Microcystic||Echogenic mass with no apparent cystic lesion(s)||Poor prognosis, often associated with fetal hydrops.|
Review of the literature reveals conflicting opinions about the association of CAM and chromosomal abnormalities. While Nyberg and colleagues point out that CAM Type II appears to be more frequently associated with other fetal abnormalities and aneuploidy, recent review of 18 CAM patients (9 of whom demonstrated CAM Type II) by Dumez et al did not reveal a single abnormal karyotype. While Callen advocates amniocentesis + karyotyping in all fetuses with CAM, Sanders and Finberg maintain a conservative position and would consider karyotyping only if fetal intervention is indicated.
A 29 year-old primigravida presented for fetal anatomy assessment at 18/40 weeks gestation. A large complex mass of mixed cystic and echogenic solid components was identified in the fetal lung. The appearance was consistent with Type II cystic adenomatoid malformation of the lung. The remainder of the fetal anatomy was difficult to visualize and detailed anatomy assessment was not completed. The patient was referred to our tertiary referral centre for further assessment and specialist obstetric care.
At this scan, the fetus was seen to be live and the size was appropriate for gestational age. Again, a large complex mass with mixed elements was identified in the fetal thorax. The heart was displaced to the left of midline, and the diaphragm was displaced inferiorly and appeared flattened. Only limited views of the heart were obtainable at this stage due to its compression and displacement by the CAM. Multiple choroid plexus cysts were identified bilaterally. The fetal stomach was not identified, but the amniotic fluid volume appeared normal.
The CAM had appeared to reduce in relative size since last scan. The interval growth had been normal and the choroid plexus cysts had resolved.
The improved accessibility of the heart revealed multiple heart defects including :
- Transposition of the Aorta
- No Identifiable Left Ventricular Outflow Tract
Large VSD and ASD were noted. The aorta originated from the right ventricle. A relatively long aortic arch was seen, and the thoracic aorta appeared to descend obliquely from right to left. The left ventricular outflow tract ( pulmonary artery in this case) was never identified, raising the possibility of pulmonary artery hypoplasia.
Also seen at this scan were overlapping digits (arthrogryposis), absent fetal stomach (presumed esophageal atresia), and mild polyhydramnios. These findings (in combination with choroid plexus cysts) were strongly suggestive of T18. Fetal umbilical blood sampling (FUBS) was determined to be the diagnostic test of choice in this case owing to the relative speed with which chromosomal analysis could be per formed. Specialist obstetric counselling was offered to the parents.
Fetal Blood Sampling Procedure
The major benefit of fetal blood sampling is the speed with which results are available (usually two to three days). The sample can be analysed immediately to confirm that it is fetal in origin and not maternal.
Fetal blood sampling confirmed female T18 karyotype. The parents decided not to continue the pregnancy.
It appears that the association of CAM and T18 in our case was not entirely coincidental. Initially, karyotyping was not offered to the patient on the basis of CAM alone. Subsequent detailed anatomy scan, did however, reveal multiple markers for aneuploidy (T18) and this resulted in invasive diagnostic testing (FUBS).
DumezY, Manderlbrot L, Radunovic N, et al: Prenatal Management of Congenital Cystic Adenomatoid Malforamtion of the Lung. J Pediatr Surg 28:36-41, 1993.
Finberg HJ: [comment] in: Year Book of Ultrasound 1994.Mosby-Year Book, 1994. p 55-56.
Nyberg DA, Mahony BS, Pretorius DH: Diagnostic Ultrasound of\par Fetal Anomalies, Text and Atlas. Mosby-Year Book, 1990. p 276-279, 712-715.
Rumack CM, Wilson SR, Charboneau, JW: Diagnostic Ultrasound, Second Edition, Vol 2. Mosby-Year Book, 1998. p 1074-1075, 1179.
Sanders RC: Structural Fetal Abnormalities, The Total Picture. Mosby-Year Book, 1996. p 6-8, 118-120.