InSight: Fluorescence in situ Hybridization (FISH), Prenatal Aneuploid Evaluation, Amniotic Fluid With Reflex to Microarray or Chromosome Analysis

CPT: 88271(x5); 88274(x2)
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Test Details

Synonyms

  • aCHG
  • CGH
  • Chromosome Analysis, Prenatal FISH, Amniotic Fluid
  • CMA
  • FISH, Prenatal
  • Karyotype, Amniotic Fluid
  • Prenatal Aneuploid Evaluation
  • Prenatal Fluorescence in situ Hybridization
  • Prenatal Reveal
  • Rapid Interphase FISH
  • WGA

Use

Rapid identification of common prenatal aneuploidy (specific for X, Y, 13, 18, 21). If abnormal, reflex to banded chromosomes to obtain fetal karyotype. This test allows prenatal detection of chromosomal rearrangements, aneuploidy, or mosaicism. Such groups include women who:

• are age 35 years or older

• have a previous child having chromosome abnormality or multiple congenital abnormalities

• have had two or more previous spontaneous abortions

• have a family history of a chromosome abnormality

• are known carriers of an X-linked disorder

• are 31 years of age or older with twin pregnancies

• have abnormal fetal ultrasound findings

• have a positive maternal serum marker screen

Additional biochemical or molecular tests may be performed on the cultured amniocytes. Fetal loss rate at 14 to 18 week sampling is considered to be 0.5%, and 2% to 3% at 10 to 13 weeks. Chorionic villus sampling (CVS) may be safer than early amniocentesis for early prenatal diagnosis of cytogenetic abnormalities. The risk of miscarriage with CVS is 1% to 1.5% but the risk of maternal infection appears to be higher with CVS than with amniocentesis. Cytogenetic analyses using such samples allow for an early gestational testing based on a 10- to 11-week placental biopsy and a 8-day cytogenetic study. Most failures are due to an inappropriate biopsy containing only maternal decidua.

Chromosomal aberration were found in 4.6% of fetuses in women older than 38 to 40 years of age. Trisomy 21 was the most common abnormality (62%). Klinefelter syndrome (11%) and trisomy 18 (11%) were next most frequent in the cases of advanced maternal age. Prenatal diagnosis is possible for more than 1000 inherited diseases. Most are inherited in an autosomal recessive manner. Antenatal molecular diagnosis has become available for cystic fibrosis, muscular dystrophy, sickle cell anemia, hemophilia, and many other genetic abnormalities. This can be done from either cultured amniotic fluid cells or chorionic villous sampling. A normal FISH result reflexes to high resolution SNP microarray which detects genomic imbalance associated with developmental delay/congenital anomalies and the percentage and location of allele homozygosity associated with uniparental disomy, recessive allele risk and identity by descent.

Limitations

FISH detects only the most common aneuploidies found in the second trimester. Abnormal results will reflex to banded chromosome analysis. Although the overall culture success rate is reported as >99%, culture failure can result. Reasons include, but are not limited to lack of amniocytes in the fluid, and contamination of the fluid with bacteria or yeast. Normal FISH results will reflex to the microarray. FISH and microarray will not detect balanced rearrangements and may not detect low level mosaicism. Extensive maternal cell contamination will limit the sensitivity of the assay.

Methodology

Fluorescence in situ hybridization (FISH) and in situ chromosome cell culturing of amniocytes to investigate numerical and/or structural chromosome abnormalities. Whole genome SNP-based copy number microarray analysis targeting 2.695 million copy number and allele-specific genome sites from uncultured cells. If DNA yield on uncultured cells is inadequate, analysis will be performed on cultured cells.

Specimen Requirements

Specimen

Amniotic fluid

Volume

25 mL or greater

Minimum Volume

25 mL

Container

Sterile plastic conical tube

Patient Preparation

The patient preferably should have had ultrasound studies (to verify fetal life, detect multiple gestation, confirm gestational age, localize fetus/placenta).

Collection

Discard first 2 mL of fluid aspirated to avoid maternal cell contamination. Specimen is collected in a 20 mL sterile syringe and transferred asceptically to sterile tubes to be transported to LabCorp. Request form is completed and accompanies specimen and miscellaneous slip to the laboratory.

Storage Instructions

Maintain specimen at room temperature.

Causes for Rejection

Specimen found not to be amniotic fluid; gross contamination with blood cells; frozen specimen; container with rubber stopper (rubber is toxic to amniocytes); quantity not sufficient for analysis

Clinical Information

Special Instructions

Pertinent medical findings should accompany request for FISH. A completed Informed Consent and Prenatal Chromosome SNP Microarray Questionnaire should accompany specimens. Call 800-345-4363 to request form. In the case of a reflex to microarray, concurrent maternal contamination (MCC) studies are recommended.

References

Chueh J, Golbus MS. Prenatal diagnosis using fetal cells in the maternal circulation. Semin Perinatol. 1990 Dec;14(6):471-482.2077667
Coppinger J, Alliman S, Lamb A, et al. Whole-genome microarray analysis in prenatal specimens identifies clinically significant chromosome alterations without increase in results of unclear significance compared to targeted microarray. Prenatal Diagn. 2009 Dec;29(12):1156- 1166.19795450
Desnick RJ, Schuette JL, Golbus MS, et al. First-trimester biochemical and molecular diagnoses using chorionic villi: High accuracy in the US Collaborative Study. Prenatal Diagn. 1992 May;12(5):357-372.1523203
DiLiberti JH, Greenstein MA, Rosengren SS. Prenatal diagnosis. Pediatr Rev. 1992 Sep;13(9):334-343.1409163
Eiben B, Trawicki W, Hammans W, et al. Rapid prenatal diagnosis of eneuploidies in uncultured amniocytes by fluorescence in situ hybridization. Evaluation of >3,000 cases. Fetal Diagn Ther. 1999 Jul-Aug;14(4):193-197.10420039
Ledbetter DH, Zachary JM, Simpson JL, et al. Cytogenetic results from the US Collaborative Study on CVS. Prenatal Diagn. 1992 May;12(5):317-345.1523201
Nicolaides K, Brizot Mde L, Patel F, Snijders R. Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 10-13 weeks' gestation. Lancet. 1994 Aug 13;334(8920):435-439. Erratum: 1994 Sep 17; 344(8925):830.7914564
Schwartz S. Efficacy and applicability of interphase fluorescence in situ hybridization for prenatal diagnosis. Am J Hum Genet. May 1993;52(5): 851-853.8488835
Tepperberg J, Pettenati MJ, Rao PN, et al. Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH): Two-year multicenter retrospective study and review of the literature. Prenat Diagn. 2001 Apr;21(4): 293-301.11288120
Wapner R. A multicenter, prospective, masked comparison of chromosomal microarray with standard karyotyping for routine and higher risk prenatal diagnosis. Abstract 1. Am J Gyn Supplement to Jan 2012.
Ward BE, Gersen SL, Carelli MP, et al. Rapid prenatal diagnosis of chromosomal aneuploidies by fluorescence in situ hybridization: clinical experience with 4,500 specimens. Am J Hum Genet. May 1993;52(2): 854-865.8488836

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