Chromosome Analysis, RAPID – Peripheral Blood or Bone Marrow for Constitutional Chromosome Complement

Rapid Constitutional Chromosome Analysis

Clinical Background

 This is a test for urgent diagnosis of genetic chromosomal anomalies associated with multiple congenital anomalies in a newborn/individual.  Decisions concerning medical intervention for life-threatening conditions in a newborn depend upon rapid evaluation of the constitutional chromosomal complement. Analysis of STAT bone marrow or peripheral blood specimen will detect gross numerical and structural abnormalities within a limited time frame.  Identification of subtle chromosome abnormalities is often not possible.

Epidemiology

 Approximately 7/1,000 live-births each year have a chromosome abnormality.  The most common congenital abnormalities include heart defects, cleft lip/palate, Down syndrome, spina bifida, all of which are associated with chromosome anomalies. Genetics

 Errors in cell division (meiosis, mitosis), advanced maternal age, and/or certain environmental exposures have been shown to result in chromosomal abnormalities.  Some types of chromosomal abnormalities may be inherited, but most occur as random events that are not passed from one generation to the next and arise either during the formation of reproductive cells or during early fetal development (for example - Turner syndrome, Down syndrome etc).

Indications for Ordering

Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB265 Indianapolis, IN. 46202-5251 Tel. 317-274-2243

 Rapid analysis for detection of numerical and structural abnormalities of autosomes and sex chromosomes for individuals with multiple congenital anomalies.  In addition, this test is often requested for infants in distress, with ambiguous genitalia, or suspected aneuploidy.

Interpretation

 Negative: A 46,XX or 46,XY karyotype indicating no apparent chromosomal abnormality is considered negative. A normal karyotype, i.e. 46,XX or 46,XY with no apparent chromosome abnormality, does not eliminate the possibility that the birth defect may be caused by submicroscopic cytogenetic lesions, molecular mutations, and/or environmental factors such as exposure to teratogens. Limitations: This analysis does not eliminate the possibility of low frequency mosaicism or small structural abnormalities. Living cells are required for chromosome analysis. As such, sample quality can affect the turnaround time.

 Positive: Identification of any numerical or structural chromosomal abnormality. A report detailing interpretation of results will be provided.

Genetic counseling is recommended for abnormal results. Methodology

 Cells are stimulated and cultured in appropriate culture medium, followed by metaphase chromosome preparation, G-banding of chromosomes and microscopic or computer analysis metaphases at 400-550 band level for bone marrow. For peripheral blood, an average band level > 550 bands is considered high resolution.  Additional staining techniques may be utilized if required.  Karyotyping involves analysis of each chromosome to determine if numerical or structural abnormalities are present in a cell. Numerical abnormalities can be either extra copies or loss of a chromosome. Structural abnormalities may involve translocations or exchange of material between chromosomes, loss or gain of a portion of a chromosome, or rearrangement of material within a chromosome.  If ordered, fluorescence in-situ hybridization (FISH) analysis of interphase cells will be performed.  Microscopic or computer analysis of at least five metaphases at 400 bands is completed for the preliminary report.

Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB265 Indianapolis, IN. 46202-5251 Tel. 317-274-2243