Chromosome Analysis, Peripheral Blood Chromosome Analysis Clinical Background A wide variety of birth defects and congenital diseases are known to be caused by chromosomal abnormalities. Common indications for chromosome studies on blood include multiple congenital anomalies, failure to thrive, developmental delay, mental retardation, possible Down syndrome, primary amenorrhea or delayed puberty, frequent miscarriages, infertility, and sex determination. G-banded karyotyping is performed for detection and visualization of numerical and structural abnormalities of autosomes and sex chromosomes as well as analysis of chromosomal rearrangements, including gains and losses. A chromosomal microarray study (CMA) is recommended for individuals with autism spectrum disorders, developmental delay and if congenital anomalies are present that are not well defined by a known syndrome. CMA is also used to detect clinically relevant gains or losses of chromosomal material that are below the limit of detection by G-banding studies. Companion fluorescence in-situ hybridization (FISH) testing may also be utilized. Epidemiology Approximately 7/1,000 live-births each year have a chromosome abnormality. Genetics Errors in cell division (meiosis, mitosis), advanced maternal age, inherited conditions, 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). Inherited chromosomal disorders may be complex, and concerns about this type of chromosomal abnormality should be discussed with a genetics professional. Indications for Ordering Family history of chromosomal abnormality Multiple congenital anomalies or birth defects Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB265 Indianapolis, IN. 46202-5251 Tel. 317-274-2243 Multiple pregnancy losses Developmental delay Post-natal peripheral blood (leukocyte) chromosomes are indicated for an array of physical and/or mental difficulties. Chromosomal microarray (CMA) is recommended for developmental delay and autism spectrum disorders. Companion fluorescence in-situ hybridization (FISH) testing may also be utilized. 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. High resolution chromosome analysis exceeds a 550 average band level. 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. References Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB265 Indianapolis, IN. 46202-5251 Tel. 317-274-2243 1. Dewald GW: Modern methods of chromosome analysis and their application in clinical practice. In Clinical Laboratory Annual. Vol 2. Edited by HA Homburger, JG Batsakis. Appleton-Century- Crofts, 1983, pp 1-29 2. Barch MJ, Knutsen T, Spurbeck JL: The AGT Cytogenetics Laboratory Manual. Third edition. 1997 3. Chromosome Abnormalities. http://www.genome.gov/11508982 4. Thompson & Thompson GENETICS IN MEDICINE: Nussbaum RL, McInnes RR, Willard, HF. 7th edition, W.B. Saunders, St. Louis 2007. Indiana University School of Medicine Division of Diagnostic Genomics - Cytogenetics Laboratory 975 West Walnut Street, IB265 Indianapolis, IN. 46202-5251 Tel. 317-274-2243 .