Constitutional Testing

Indications

These may include, but are not limited to:

  • A fetus, a baby, or an adult with multiple congenital abnormalities
  • Personal or family history of chromosome abnormalities
  • Suspicion of sex chromosome abnormalities
  • Infertility or history of multiple pregnancy losses
  • Developmental delay (DD), or intellectual disability (ID)
  • Autism spectrum disorder
  • Growth abnormalities
  • Spontaneous fetal demise
  • Increased risk for a chromosome abnormality, due to maternal age, family history, or personal history
  • Fetal abnormalities detected on ultrasound
  • Increased risk identified by prenatal screening techniques
  • Parental concern

Recommendation: The American College of Medical Genetics guidelines for the use of microarray-based technology, Genetics In Medicine • Volume 12, Number 11, 2010, provides the following recommendations:

  1. Cytogenomic Microarray Analysis (CMA) testing for CNV (copy number variant) is recommended as a  first-line test in the initial postnatal evaluation of individuals with the following:
    1. Multiple anomalies not specific to a well-delineated genetic syndrome
    2. Apparently non-syndromic developmental delay or intellectual disability
    3. Autism spectrum disorders
  2. Further determination of the use of CMA testing for the evaluation of the child with growth retardation,  speech delay, and other less well-studied indications is recommended, particularly by prospective studies and  aftermarket analysis.

Recommendation: In an article entitled "Chromosomal microarray versus karyotyping for prenatal diagnosis", (published in N Engl J Med. 2012; 367(23):2175-84) Wapner RJ et al. state:

"In the context of prenatal diagnostic testing, chromosomal microarray analysis (CMA) identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies."

Specimen types

Testing to detect chromosomal and genomic abnormalities can be performed on:

  • amniotic fluid
  • chorionic villi
  • peripheral blood
  • umbilical cord blood
  • skin biopsy
  • products of conception
  • fetal tissue
  • saliva
  • extracted DNA

See Sample Collection Instructions

Tests and Services

Available testing options include:

  • Cytogenomic Microarray Analysis (CMA) detects imbalances in the genome (copy number changes due to aneuploidy, deletions, or duplications) at high resolution and genomic regions of homozygosity (copy neutral absence of heterozygosity). This test does not detect balanced rearrangements. 
  • G-banded chromosome analysis or karyotyping (routine) detects imbalances (aneuploidy, deletions, or duplications) in the genome at low resolution. This test can detect balanced rearrangements and can be used to distinguish free trisomy from translocation-associated trisomy. In cases of familial chromosomal rearrangements a family follow-up test is available.
  • G-banded chromosome analysis or karyotyping (mosaicism): The number of cells evaluated is increased, for better detection of a second cell type present at a low level.
  • STAT IFISH (interphase fluorescence in situ hybridization) for aneuploidy using a panel of probes for chromosomes 13, 18, 21, X, and Y detects aneuploidy for these chromosomes.
  • FISH for specific microdeletion and microduplication syndromes. See list of probes below or call 206-598-4488 for additional probe availability.
  • Subtelomere FISH detects cryptic balanced and unbalanced reciprocal translocations too small to see with G-banded chromosome analysis.
  • Y-PCR analysis detects microdeletions of the Y chromosome associated with male infertility
  • Grow cell cutures for sendout testing: Cultures of amniocytes, chorionic villus cells, fetal tissue, or skin fibroblasts can be established in our laboratory and sent elsewhere for other types of testing.

Constitutional FISH microdeletion/duplication tests

Disease Chromosome abnormality
1p36.3 Deletion Syndrome Deletion 1p36.3
Wolf-Hirschorn Syndrome Deletion 4p16.3
Cri du Chat Syndrome Deletion 5p15.2
Sotos Syndrome Deletion 5q35
Williams Syndrome Deletion 7q11.23
Williams-Beuren Region Duplication Duplication 7q11.23
Langer-Giedion Syndrome Deletion 8q24
Pallister-Killian Syndrome iso12p mosaicism
Prader-Willi Syndrome Deletion 15q11.2
Angelman Syndrome Deletion 15q11.2
15q11.2 Duplication Syndrome (Autism) Duplication 15q11.2
Miller-Diecker Syndrome Deletion 17p13.3
Potocki-Lupski Syndrome Duplication 17p11.2
Smith-Magenis Syndrome Deletion 17p11.2
DiGeorge/Velocardiofacial Syndrome Deletion 22q11.2
22q11.2 Duplication Syndrome Duplication 22q11.2
Short Stature Deletion Xp22.33 (SHOX)
X-linked Ichthyosis Deletion Xp22.33 (STS)
Kallman Syndrome Deletion Xp22.3 (KAL1)
X inactivation Presence/Absence XIST
46,XX Testicular DSD/46,XY DSD/46,XY CGD Presence/Absence SRY