Test ID: CGH
Array Comparative Genomic Hybridization (aCGH), Whole Genome, Constitutional

As a first-tier, postnatal test per the American College of Medical Genetics (ACMG)’s practice guidelines for individuals with multiple anomalies not specific to well-delineated genetic syndromes, individuals with apparently nonsyndromic developmental delay or intellectual disability and individuals with autism spectrum disorders.

As an appropriate follow-up for individuals with unexplained developmental delay/intellectual disability, autism spectrum disorders, or multiple congenital anomalies with a previously normal conventional chromosome study due to the superior resolution of the chromosomal microarray testing. 

Determining the size, precise breakpoints, and gene content, and unveiling unappreciated complexity of abnormalities detected by other methods such as conventional chromosome and FISH studies.

Determining if apparently balanced abnormalities identified by previous conventional chromosome studies have cryptic as a large proportion of such rearrangements appear balanced at the resolution of a chromosome study, but may actually be unbalanced when analyzed by higher-resolution chromosomal microarray.

Aneuploidy or unbalanced chromosome rearrangements are often found in patients with mental retardation, developmental delay, autism, dysmorphic features, or multiple congenital anomalies. Some pathogenic chromosome imbalances are large enough to be detected with conventional chromosome analysis, however many pathogenic rearrangements are at or below the limits of resolution of chromosome analysis (approximately 5 megabases).

Array comparative genomic hybridization (aCGH) is a method for detecting copy number differences (gains or losses) across the entire genome in a single assay. This test provides a molecular karyotype and has a minimum functional resolution of approximately 100 kilobases throughout the genome. In addition, higher resolution coverage of targeted regions has a minimum functional resolution of approximately 20 kilobases. Targeted regions include common microdeletion and microduplication syndromes, many genes involved in Mendelian disorders, and the pericentromeric and subtelomeric regions of the genome.

As a participant in the International Standard Cytogenomic Array Consortium (ISCA), Mayo Clinic Cytogenetics Laboratory contributes submitted clinical information and test results for molecular cytogenetic tests to a HIPAA-compliant, de-identified public database hosted by the National Institute of Health. This is an international effort to improve diagnostic testing and our understanding of the relationships between genetic changes and clinical symptoms (for information about the database visit the consortium website at https://isca.genetics.emory.edu). Confidentiality of each sample is maintained. Patients may request to opt-out of this scientific effort by calling the laboratory at 1-800-533-1710, extension 8-2952 and asking to speak with a laboratory genetic counselor. Please call with any questions.

An interpretive report will be provided.

When interpreting results, the following factors need to be considered:

-Copy number variation is found in patients with abnormal phenotypes and benign variations are found in all individuals. Therefore the differentiation between pathogenic and benign copy number variation can be challenging.

-While most copy number variations observed through chromosomal microarray testing can readily be characterized as pathogenic or benign, a subset have limited data available to support classification into either of these categories. In these situations, a number of considerations must be taken into account to help interpret the data, such as the nature of the imbalance, the size and gene content of the interval, mode of inheritance, and the presence of the variation in a parent.

-The continual discovery of novel copy number variation and new reports classifying specific copy number variation as pathogenic or benign enter the literature frequently, thus the interpretation of any given copy number variation may evolve rapidly as more information becomes available.

It is recommended that a qualified professional in Medical Genetics communicate all abnormal results to the patient.

This test does not detect balanced chromosome rearrangements such as Robertsonian or other reciprocal translocations, inversions, balanced insertions, and some cases of polyploidy.

This test is not designed to detect mosaicism, although it can be detected in some cases.

This test does not detect DNA sequence changes (point mutations) or other types of mutations such as epigenetic changes.

The results of this test may be of uncertain clinical significance. In such cases, studies of additional family members may be required to help interpret the results.

1. Miller DT, Adam MP, Aradhya S, et al: Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010; 86:749-764

2. Manning M, Hudgins L: Professional Practice and Guidelines Committee: Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010;12(11):742-745

• Informed Consent for Genetic Testing
• Cytogenetics-Array CGH Testing Patient Information Sheet
• Chromosomal Microarray Testing and the ISCA Consortium Database