Trisomy 18 Workup

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 11, 2011
 

Laboratory Studies

  • Hematological studies in patients with trisomy 18 during the first week of life
    • Thrombocytopenia: This is the most common hematological abnormality detected, occurring in 83% of those with trisomy 18; some patients need platelet transfusions.[11]
    • Neutropenia: This is the second most commonly detected abnormality. Neutrophil concentrations exceeding the reference range for age were reported in 42% of patients with trisomy 18.[11]
    • Abnormal erythrocyte values: This is the third most common hematological abnormality detected. Only 43% of patients with trisomy 18 had normal erythrocyte values;[11] anemia was detected in 40%, and polycythemia was detected in 17%.
  • Conventional cytogenetic studies
    • Full trisomy 18 (about 95% of cases)
    • Trisomy 18 mosaicism (about 5% of cases)
    • Translocation type trisomy 18 syndrome (very rare)
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Imaging Studies

  • Echocardiography is indicated for cardiac anomalies: In a study from Lin et al, the anomalies identified included ventricular septal defect (94%), patent ductus arteriosus (77%), atrial septal defect (68%), and complex congenital heart defects (32%).[12]
  • A barium swallow is indicated for GI anomalies.
  • In Lin et al's study, using brain ultrasonography, the most common brain lesion revealed was cerebellar hypoplasia (32%), followed by brain edema (29%), enlarged cisterna magna (26%), and choroid plexus cysts (19%).[12] Ultrasonography is also indicated for genitourinary anomalies.
  • Skeletal radiography is used to discern phocomelia, absent radius, tight flexion of the fingers with the second over the third and the fifth over the fourth, talipes equinovarus, short sternum, hemivertebrae, fused vertebrae, short neck, scoliosis, rib anomaly, and dislocated hip.
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Other Tests

Prenatal screening in families without history of trisomy 18 using maternal serum markers

  • Low levels of human chorionic gonadotrophin (hCG) and low unconjugated estriol (uE3) in maternal serum during mid trimester are useful predictors for an increased risk for trisomy 18.
  • A first-trimester biochemical screening for trisomy 18 is possible because a recent retrospective study revealed reduced levels of pregnancy-associated plasma protein A (PAPP-A) and free beta–human chorionic gonadotropin (β-hCG) at 8-13 weeks' gestation
  • The multiples of the mean (MoM) in affected pregnancies was 0.25 for PAPP-A and 0.34 for free beta-hCG.
  • Screening for trisomy 18 using a combination of maternal age, PAPP-A, and beta-hCG has a detection rate of 76.6% with a false-positive rate of 0.5%.
  • Additional studies are required to confirm these findings.

Prenatal ultrasonography

  • Most fetuses with trisomy 18 have detectable structural abnormalities.
  • Ultrasonographic abnormalities include microcephaly and Dandy-Walker malformation (posterior fossa enlargement associated with cerebellar hypoplasia).
  • Choroid plexus cysts may be present.
  • Visceral anomalies are common and include GI anomalies (eg, omphalocele, esophageal atresia), congenital heart defects (eg, septal defect with polyvalvular disease), and renal anomalies (eg, polycystic enlarged horseshoe kidneys, ectopic kidneys).
  • Fetuses typically have overlapping digits, with the second and fifth fingers overlapping the third and fourth fingers, respectively. Overall posturing of the wrists suggests contractures, clubfeet, and rocker-bottom feet.
  • The frequencies of congenital anomalies detectable with prenatal ultrasonography are as follows:
    • Persistent abnormal position of fetal fingers - 89%
    • Choroid plexus cysts - 43%
    • Abnormally shaped fetal head (strawberry or lemon) - 43%
    • Two-vessel umbilical cord - 40%
    • Cardiac defects - 37%
    • Intrauterine growth retardation - 29%
    • Omphalocele - 20%
    • Neural tube defects - 9%
    • Cystic hygroma or lymphangiectasia - 14%
    • Oligohydramnios/polyhydramnios - 12%
    • Renal defects - 9%
  • First trimester ultrasonographic findings in fetuses with trisomy 18[13]
    • Nuchal translucency (> 95th percentile) - 91%
    • Nuchal translucency (> 99th percentile) - 77%
    • Absent/hypoplastic nasal bone - 53%
    • Generalized subcutaneous edema - 49%
    • Omphalocele - 21%
    • Abnormal posturing of hands - 6%
    • Megacystis - 4%
    • Cardiac defect - 4%
    • Pleural effusions - 4%
    • Echogenic yolk sac - 4%
    • None - 2%

Three-dimensional and 4-dimensional ultrasonography [14]

  • These offer diagnostic advantages for many anomalies associated with trisomy 18, especially for anomalies of the extremities and face. These studies can be a powerful adjunct to 2-dimensional ultrasonography in the prenatal anatomic evaluation of fetuses with trisomy 18.

Fetal echocardiography

  • Abnormal cardiac findings are detectable using echocardiography in most patients with trisomy 18.
  • A wide spectrum of heart defects is observed.
  • Heart malformations can be reliably diagnosed, even in the first trimester at the time of nuchal translucency measurement.

Prenatal diagnosis

  • Amniocentesis is routinely performed at 14-16 weeks' gestation. It remains the criterion standard with which all other invasive diagnostic tests are compared. Amniocentesis testing for chromosome disorders is 99.5% accurate and is associated with a small risk of pregnancy loss (about 1 in 200-300).
  • Chorionic villus sampling (CVS) is performed at 10-13 weeks' gestation. An earlier CVS test is thought to be associated with a small risk (1 in 300-1000) of fetal transverse limb deficiency, a small chance of maternal cell contamination, and a 0.5-1% risk of fetal loss after the procedure. The accuracy (96-98%) is less than that of mid trimester amniocentesis because of confined placental mosaicism and maternal cell contamination.
  • Percutaneous umbilical blood sampling (PUBS) is of limited use, except in cases detected late in pregnancy. The preimplantation diagnosis is not of any realistic relevance for current care.
  • False positive prenatal diagnosis of trisomy 18 using fluorescence in situ hybridization (FISH) has been reported due to rare familial variants involving the failure of hybridization of α-satellite DNA or hybridization to false target chromosomes.[15] This underscores the necessity to adhere to the American College of Medical Genetics guidelines for interpretation of FISH results.
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Contributor Information and Disclosures
Author

Harold Chen, MD, MS, FAAP, FACMG  Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael Fasullo, PhD  Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College

Michael Fasullo, PhD is a member of the following medical societies: American Society for Biochemistry and Molecular Biology, Environmental Mutagen Society, Genetics Society of America, and Radiation Research Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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Infant with Edwards syndrome. Note microphthalmia, micrognathia/retrognathia, microstomia, low set/malformed ears, short sternum, and abnormal clenched fingers.
Note the characteristic clenched hand with the index finger overriding the middle finger and the fifth finger overriding the fourth fingers.
A G-banded karyotype showing 47,XY,+18.
Note a rocker-bottom foot with prominent calcaneus.
Hands of a fetus with Edwards syndrome. Note that fetus typically presents with overlapping digits with the second and fifth fingers overriding the third and fourth fingers respectively. Overall posturing of the wrists and fingers suggests contractures.
 
 
 
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