Array comparative genomic hybridization (aCGH) is used as a diagnostic tool for individuals with unexplained developmental delay (DD), autism spectrum disease (ASD) and mental retardation (MR).  aCGH is used, in addition to clinical evaluation and conventional genetic testing.  Conventional cytogenetic analysis (e.g., G-banded karyotyping, FISH assays and subtelomeric screening) is limited by its low resolution and low diagnostic yield.  aCGH provides a higher resolution which allows for the detection of smaller genetic abnormalities not detectable by conventional assays.  The genetic abnormalities are expressed as copy number variations (CNVs) which are deletions or duplications of large segments of genomic material.  This technique is not used to detect small copy-number changes.  aCGH does not detect balanced chromosome rearrangements in which there is no gain or loss of DNA (balanced inversions or balanced translocations).

This document addresses aCGH only and does not address karyotyping, FISH, or other genetic molecular testing.

Medically Necessary:

Cytogenetic microarray (CMA) testing for copy number variation (CNV) is considered medically necessary 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; or
2. Apparently non-syndromic developmental delay/intellectual disability; or
3. Autism spectrum disorders.

Investigational and Not Medically Necessary: 

Cytogenetic microarray (CMA) testing for copy number variation (CNV) is considered investigational and not medically necessary for individuals with developmental delay, autism spectrum disorder, and mental retardation when the above criteria are not met.

The DNA-based technique CGH microarray analysis has been used in the evaluation of tumors and individuals with cancer in the past, and it is now being applied in the assessment of individuals demonstrating idiopathic MR or DD, dysmorphic features, congenital anomalies, and spontaneous abortions. 

In a 2006 clinical report by the American Academy of Pediatrics addressing the clinical genetic evaluation of children with DDor MR, microarray CGH is referred to as an "emerging technology."  The authors note that while some clinical geneticists have begun to take advantage of this testing technique in individuals with undiagnosed developmental delay/mental retardation (DD/MR), there are currently insufficient published reports of the use of this technology in the evaluation of the child with DD/MR (Moeschler, 2006).

In 2007, guidelines published by the American Academy of Pediatrics on the Identification and Evaluation of Children With Autism Spectrum Disorders indicated that CGH microarray analysis is a promising tool that may become standard of care in the future, but this technique had not yet been evaluated systematically in children with ASDs (Johnson, 2007).  That same year, the American College of Medical Genetics (ACMG) guidelines for the use of array-based technology in the practice of medical genetics were originally published.  This guideline recommended that "Microarray CGH may be used as an adjunct to standard cytogenetic testing (including targeted FISH for specific microdeletion/duplication syndromes) in the evaluation of a patient with mental retardation and/or congenital anomalies.  Financial limitations, availability of parents for testing, and the possible ambiguity of results should all be considered."  As indicated below (Manning, 2010), the ACMG has since revised its position regarding the use of microarray CGH in individuals with developmental delay (intellectual disability) and autism spectrum disorders. 

In 2008, the ACMG published guidelines addressing clinical genetics evaluation in identifying the etiology of ASDs.  These guidelines state that aCGH has emerged as a powerful new tool that promises further revolution of clinical genetic testing.  aCGH is recommended as a second tier evaluation tool with the possibility of becoming a first tier test when advances in aCGH show improvement in technique and diagnostic yield.  The guideline also provides a discussion of the value of genetic evaluations in light of the fact that the genetic tests are costly and the information obtained typically will not change clinical interventions.  According to the authors, "a definitive diagnosis helps the patient acquire needed services, and is helpful in many other ways for the family.  Many families are greatly empowered by knowledge of the underlying cause of a relative's disorder.  Depending on the etiology, associated medical risks may be identified that lead to screening and the potential for prevention of morbidity" (Schaefer, 2008).

The American College of Obstetrics and Gynecology Committee on genetics published a statement on the use of aCGH in prenatal diagnosis (2009).  The guideline addresses the expanding use of aCGH for the diagnosis of genomic rearrangements in children with idiopathic mental retardation, developmental delay and multiple congenital anomalies.  The guideline states that "The use of array CGH technology in prenatal diagnosis is currently limited by several factors, including the inability to detect balanced chromosomal rearrangements, the detection of copy number variations of uncertain clinical significance, and significantly higher costs than conventional karyotype analysis.  Although array CGH has distinct advantages over classic cytogenetics in certain applications, the technology is not currently a replacement for classic cytogenetics in prenatal diagnosis."

The American College of Obstetrics and Gynecology Committee on genetics published a statement on the use of aCGH in prenatal diagnosis (2009).  The guideline addresses the expanding use of aCGH for the diagnosis of genomic rearrangements in children with idiopathic mental retardation, developmental delay and multiple congenital anomalies.  The guideline states that "the use of array CGH technology in prenatal diagnosis is currently limited by several factors, including the inability to detect balanced chromosomal rearrangements, the detection of copy number variations of uncertain clinical significance, and significantly higher costs than conventional karyotype analysis.  Although array CGH has distinct advantages over classic cytogenetics in certain applications, the technology is not currently a replacement for classic cytogenetics in prenatal diagnosis."

In 2009, a Blue Cross Blue Shield Association Special Report, aCGH for the Genetic Evaluation of Patients with Developmental Delay/Mental Retardation or Autism Spectrum Disorder highlighted the fact that CGH arrays have the advantage of greatly improved resolution, which allows detection of smaller, clinically significant genomic abnormalities not detectable by conventional assays (improving diagnostic yield), and more exact locus definition of conventionally detectable abnormalities (improving information for genotype-phenotype correlation).  The authors emphasize that the results of neither conventional cytogenetic evaluation nor of aCGH evaluation have been systematically studied for impact on clinical outcomes other than diagnostic yield, which is an intermediate outcome.  Impact of testing on the kinds of outcomes that matter to the individual [or child] has been directly addressed in very few studies.  Thus, it is not possible to draw evidence-based conclusions regarding the clinical utility of aCGH genetic evaluation.  The assessment points out that expert consensus and clinical guidelines state that genetic information is of value because: (1) it establishes a causal explanation that is helpful to families; (2) it avoids additional consultations and various types of diagnostic tests, (3) it assists with early and improved access to community services that may ameliorate or improve behavioral and cognitive outcomes; and (4) it provides estimates of recurrence rates to better guide reproductive decision-making, and enables an understanding of prognosis and future needs.  However, the authors state that little evidence supports these outcomes.  The report concludes that aCGH technology is rapidly evolving and different kinds of arrays with different capabilities of detecting genomic abnormalities are clinically available from different laboratories; it is up to the ordering physician to know the limits of the particular technology employed by the laboratory.

Hochstenback and colleagues (2009) reviewed the outcome of cytogenetic studies in all 36,325 DD/MR referrals in the Netherlands during a period (1996 – 2005) before the advent of array-based genome investigation.  The authors found that in a minimum of 0.78% of all referrals a balanced chromosomal rearrangement would have remained undetected by array-based investigation.  These include familial rearrangements (0.48% of all referrals), de novo reciprocal translocations and inversions (0.23% of all referrals), de novo Robertsonian translocations (0.04% of all referrals), and 69, XXX triploidy (0.03% of all referrals).  The authors concluded that karyotyping, following an initial array-based investigation, would give only a limited increase in the number of pathogenic abnormalities, i.e. 0.23% of all referrals with a de novo, apparently balanced, reciprocal translocation or inversion (assuming that all of these are pathogenic), and 0.03% of all referrals with 69,XXX triploidy.  The authors suggest that the introduction of high resolution, array-based genome examination as the initial genetic test will lead to a detection rate of approximately 19% of the pathogenic aberrations in unselected individuals with idiopathic DD/MR. The authors recommended that, because of its high diagnostic yield, high-resolution array-based genome investigation should be the first investigation performed in cases of DD/MR.

The Hochstenback article also provides a discussion of the value of the early identification of the cause of DD/MR.  The authors state that "Early identification of an underlying genetic aetiology is of great importance to the patient and the family.  First, it will provide appropriate treatment options and enable presymptomatic screening for complications that are associated with the disorder.  Second, a short and long term prognosis can be inferred, enabling educational and other forms of assistance.  Third, an assessment of the recurrence risk, in the context of reproductive counselling, can be given, and carrier identification as well as prenatal diagnosis may become available.  Fourth, the family can be referred to appropriate medical and social services and support groups.  Finally, recognition of the aetiology will eliminate additional, superfluous, time and resource consuming testing.  Despite the availability of an extensive range of diagnostic investigations, the underlying aetiology remains elusive in 50–80% of DD/MR patients."

Sagoo and colleagues (2009) updated the findings of a systematic review and meta-analysis on array CGH in individuals with learning disability (mental retardation) and congenital anomalies.  The analysis included 19 studies (13,926 subjects), of which 12 studies (13,464 subjects) were published since the previous analysis.  The overall diagnostic yield of causal abnormalities was 10% (95% confidence interval: 8-12%).  The overall number needed to test to identify an extra causal abnormality was 10 (95% confidence interval: 8-13).  The overall false-positive yield of noncausal abnormalities was 7% (95% confidence interval: 5-10%).  The authors concluded that the updated meta-analysis provides new evidence to support the use of array-based CGH in investigating individuals with learning disability and congenital anomalies in whom conventional cytogenetic tests have proven negative.  However, the authors cautioned that this technology also identifies false positives at a similar rate to causal variants, so caution in clinical practice is appropriate.

The American Academy of Pediatrics published the findings of a comparison study of 933 individuals who received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008.  The clinical genetic testing included fragile X testing, G-banded karyotype and CMA to test for submicroscopic genomic duplications and deletions.  Based on the findings in this article, genetic diagnosis will be missed in at least 5% of ASD cases without CMA.  The authors expressed that "specific clinical recommendations for including CMA as a first-tier test in the evaluation of patients with ASD have not kept pace with this rapidly evolving technology" and concluded that CMA resulted in the highest detection rate among clinically available genetic tests for individuals with ASD.  The authors discussed the potential added clinical impact of CMA, especially in comparison with G-banded karyotype testing, and they suggest that CMA could lead to the establishment of a diagnosis that may lead to earlier intervention and consequently improved outcomes (for example, in cases where some clinical symptoms of ASD are apparent before the age of 3 years, but the children may not be diagnosed until they are much older).  In this example, the clinical diagnosis of ASD would not change but identifying a clear genetic etiology could be advantageous.  "A clear genetic diagnosis can affect patient management decisions, availability of developmental services, and accuracy of genetic counseling about recurrence risks, which may range from 5% to as high as 50% depending on the cause.  A clear genetic diagnosis also spares the patient and family a diagnostic odyssey involving multiple rounds of diagnostic testing." (Shen, 2010)

The ACMG guidelines were updated in 2010 to address the utility and limitations of array-based technology for utilization in medical genetics practice for detection of chromosome abnormalities.  The guideline acknowledges that aCGH analysis provides sensitive and reliable information in detecting submicroscopic chromosomal abnormalities that are undetectable by current cytogenetic testing methodologies but there are some limitations on the value of the information available from this test.  "Array CGH cannot identify balanced chromosomal rearrangements such as translocations or inversions or differentiate free trisomies from unbalanced Robertsonian translocations.  Some aneuploidies can be missed, such as XYY if the wrong gender control is used.  Marker chromosome may also be missed, depending on the size, marker composition and array coverage of the specific chromosomal region present on the marker … Interpretation of the significance of a rare copy number change can be incomplete if parental samples are unavailable for comparison …  Finally, triploidy will not be detected by some forms of microarray."  The guidelines make the following recommendations:

• CMA testing for CNV is recommended as a first-line test in the initial postnatal evaluation of individuals with the following:
  • Multiple anomalies not specific to a well-delineated genetic syndrome
  • Apparently non-syndromic developmental delay/intellectual disability
  • ASDs
• 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 via prospective studies and aftermarket analysis.

Appropriate follow up is recommended in cases of chromosome imbalance identified by CMA, to include cytogenetic/FISH studies of the child, parental evaluation, and clinical genetic evaluation and counseling (Manning, 2010). 

The International Standard Cytogenomic Array (ISCA) Consortium convened two international workshops and conducted a literature review of 33 studies, including 21,698 individuals who underwent CMA.  The evidence-based summary of clinical cytogenetic testing compared CMA to G-banded karyotyping with respect to the technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation.  The authors concluded that CMA offers a much higher diagnostic yield (15%–20%) for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID) ASD, or multiple congenital anomalies (MCA) than a G-banded karyotype (~3%, excluding Down syndrome and other recognizable chromosomal syndromes).  The ISCA Consortium recommends the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for individuals with DD/ID, ASD, or MCA.  G-banded karyotype analysis should be reserved for individuals with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.  The ISCA notes that geneticists, pediatric neurologists, and developmental pediatricians are increasingly ordering CMA to obtain a genetic diagnosis for children with unexplained DD/ID, ASD, and MCA.  A specific genetic diagnosis facilitates comprehensive medical care and accurate recurrence risk counseling for the family (Miller, 2010). 

Hillman and colleagues (2011) published the findings of a systematic review and meta-analysis designed to determine whether array CGH testing in the prenatal population provides diagnostic information over conventional karyotyping.  Electronic searches of the MEDLINE (1970 to December 2009), EMBASE (1980 to December 2009) and CINAHL (1982 to December 2009) databases were conducted.  Studies were chosen if aCGH was used on prenatal samples or if aCGH was used on postnatal samples following termination of pregnancy for structural abnormalities that were detected on an ultrasound scan.  The researchers found that aCGH detected 3.6% (95% CI, 1.5-8.5) additional genomic imbalances when conventional karyotyping was 'normal', regardless of referral indication.  This increased to 5.2% (95% CI, 1.9-13.9) more than karyotyping when the referral indication was a structural malformation on ultrasound.  The researchers concluded that there appears to be an increased detection rate of chromosomal imbalances, compared with conventional karyotyping, when array CGH techniques are employed in the prenatal population.  However, the fact that some are copy number imbalances which are not clinically significant carries implications for prenatal counseling and maternal anxiety.

It is also worth noting that since the publication of the practice guideline recommending CMA as a first-line test in DD/ID and ASD (Manning et al 2010), the ACMG has published policy statements, standards, and guidelines for the design and performance expectations of CMAs (Kearney, 2011a) and for the interpretation and reporting of CNVs (Kearney, 2011b).

In summary, aCGH technology is rapidly evolving and in its current state of development, does have some limitations.  Abnormalities detected by aCGH are based on a change in the balance of the DNA between the control and sample.  Because of this, aCGH does not detect rearrangements in which there is no balance change in the DNA such as balanced translocations and inversions.  Also, because aCGH cannot identify the cause of changes in the DNA copy number, (duplication; an insertion; a marker chromosome; or an unbalanced translocation), FISH analysis may then be necessary to identify the specific mechanism which caused the change.  However, in spite of these limitations, there may be circumstances when aCGH testing is appropriate.  Studies in the published peer-reviewed scientific literature have reported that when used in conjunction with conventional cytogenetic testing, comparative aCGH identified a higher sensitivity for known chromosomal abnormalities and a diagnostic yield of greater than more sensitive diagnostic tool than pre-existing methods of chromosome analysis.  There is also some evidence that aCGH provides valuable information to clinicians who are attempting to identify a definitive diagnosis in individuals with unexplained DD, ASDs and MR.  The determination of a definitive diagnosis can be helpful in obtaining needed services for the affected individual, empowering families by providing accurate recurrence risk counseling and knowledge of the underlying cause of a relative's disorder.  A clear genetic diagnosis may also spare the affected individual and family multiple rounds of diagnostic testing.  The results of aCGH testing may also provide genetic data which can be used to assist parents to plan future pregnancies to preclude the birth of future affected children.  While there remain questions regarding the clinical utility of aCGH, increasingly, geneticists, pediatric neurologists, and developmental pediatricians are using CMA to obtain a genetic diagnosis for children with unexplained DD, ASD, and MR.  In spite of its limitations, when consideration is given to its potential benefits, aCGH testing may be appropriate in select individuals with unexplained DD, ASD and MR which cannot be confirmed by clinical presentation or through conventional genetic testing.

Comparative Genomic Hybridization Testing (CGH) Microarray Testing 

Numerous disorders associated with birth defects or developmental problems are believed to be caused by copy number variants (the deletion or duplication of genomic material).  Cytogenetic testing may be requested in order to identify genetic imbalances in infants or children with characteristics of developmental delay, autism spectrum disorder (ASD) or mental retardation.

Historically, fluorescence in situ hybridization (FISH) and G-banded karyotyping were the primary tests used to identify genetic imbalances in infants or children believed to have developmental delay, autism spectrum disorder or mental retardation.  FISH utilizes short DNA probe sequences that are labeled with a fluorescent dye that glows (fluoresces) under UV light.  These labeled DNA probes bind only to specific regions within the genome and can identify small chromosomal duplications or deletions.  G-banded karyotyping uses Giemsa stain to identify chromosomal aberrations such as translocations and rearrangements. 

aCGH is a more recently developed cytogenetic technique intended to combine the speed of DNA analysis with a large capacity to scan for genomic abnormalities in a single assay.  aCGH increases the chromosomal resolution and permits the identification of more copy number variations (CNVs).  As a result, aCGH increases the diagnostic yield and permits visualization of genomic detail beyond that of conventional methods and may detect genomic gains or losses not identified by G-banded karyotyping.  aCGH only detects unbalanced chromosomal changes.  Structural chromosome aberrations such as balanced reciprocal translocations or sequence inversions are not identified with comparative genomic hybridization (CGH) because they do not change the copy number.  The terms aCGH, chromosomal microarray analysis (CMA), CGH microarray analysis and microarray-based CGH are often used interchangeably,

There are at a minimum two types of aCGH platforms.  Targeted (constitutional) aCGH provides high-resolution coverage of the genome primarily in areas containing known, clinically significant CNVs.  Whole-genome arrays provide high resolution coverage of the entire human genome and may identify new CNVs for which the clinical significance is not yet known and new genetic syndromes.

Developmental Delay, Autism Spectrum Disorder and Mental Retardation 

Developmental delay occurs when a child has not reached a developmental milestone by the expected time period. For example, if the normal age span for learning to walk is between 9 and 15 months, and a 24-month-old child has still not begun walking, this would be considered a developmental delay.  Developmental delay can occur in one or many areas—for example, thinking (cognitive), gross or fine motor, language or social skills.  Also, developmental growth in one area is related to developmental growth in another area.  For example, if an individual has a delay in one area (e.g., speech and language), it will likely influence development in another area (e.g., social and emotional).

ASDs are a group of neurodevelopmental disorders defined by measurable impairments in communication and social interactions, restricted interests and activities, and stereotypical behaviors.  Abnormalities in these three developmental areas tend to occur together in affected individuals.  The social skills that develop normally in typically-developing children do not do so in children with ASDs.  The cognitive abilities of people with ASDs can vary from gifted to severely challenged.  While autistic disorder is the most commonly known type of pervasive developmental disorder (PDD), PDD's also include

• Autism Spectrum Disorders (or Autistic Spectrum Disorders, ASD) which is a subcategory including autism, Asperger's syndrome, and pervasive developmental disorder not otherwise specified
• Childhood Disintegrative Disorders (CDD)
• Rett syndrome

Mental retardation (intellectual disability, cognitive disability) is characterized by a significantly below-average score on a test of mental ability or intelligence in addition to limitations in the ability to function in areas of daily life, such as self-care, communication, social interactions and school activities.  Individuals with mental retardation can and do learn new skills, but they develop more slowly than children with average intelligence and adaptive skills.  The degree of mental retardation varies from one individual to another and may range from mild to profound.  An individual's level of mental retardation can be defined by their intelligence quotient or by the amount and type of support they need.

Balanced Reciprocal Translocations: An equal exchange of material between chromosomes.

Comparative Genomic Hybridization (CGH): A molecular technique that is used to detect chromosome gain or loss by hybridizing DNA from a target cell and a normal cell.

Congenital Anomaly: A defect that is present at birth and may be the result of either environmental or genetic factors, or both.

Copy Number Variants (CNVs): An alteration of the DNA of a genome that results in the cell having an abnormal number of copies of one or more sections of the DNA.

Cytogenetics: A branch of genetic science that focuses on the study of the structure and function of the cell, especially the chromosomes.  Cytogenetics includes but is not limited to G-banded karyotyping, fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH).

G-banded Karyotyping: A molecular chromosome analysis technique which employs Giemsa dye to stain DNA strands.

Karyotypes:  The number and appearance of chromosomes under a light microscope.

Sequence Inversions: The same sequence is present in reverse base pair order.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Medically Necessary:

When services may be Medically Necessary when criteria are met:
For the procedure codes listed above for all other diagnoses not listed when medically necessary criteria are met.

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above for all other diagnoses not listed when criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding.

Peer Reviewed Publications: 

1. Hillman SC, Pretlove S, Coomarasamy A et al. Additional information from array comparative genomic hybridization technology over conventional karyotyping in prenatal diagnosis: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2011; 37(1):6-14.
2. Hochstenbach R, van Binsbergen E, Engelen J, et al. Array analysis and karyotyping: workflow consequences based on a retrospective study of 36,325 patients with idiopathic developmental delay in the Netherlands. Eur J Med Genet. 2009; 52(4):161-169.
3. Kearney HM, South ST, Wolff DJ, et al. American College of Medical Genetics recommendations for the design and performance expectations for clinical genomic copy number microarrays intended for use in the postnatal setting for detection of constitutional abnormalities. Genet Med. 2011a; 13(7):676-679.
4. Kearney HM, Thorland EC, Brown KK, et al. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 201lb; 13(7):680-685.
5. Sagoo GS, Butterworth AS, Sanderson S, et al. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med. 2009; 11(3):139-146.
6. Shen Y, Dies KA, Holm IA, et al. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. 2010; 125(4):e727-735.

Government Agency, Medical Society, and Other Authoritative Publications:

1. ACOG Committee opinion no.446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol. 2009; 114(5):1161-1163.
2. Blue Cross Blue Shield Association Technology Evaluation Center (TEC). TEC Special Report: Array Comparative Genomic Hybridization (aCGH) for the Genetic Evaluation of Patients with Developmental Delay/Mental Retardation and Autism Spectrum Disorder. TEC Assessments 2009; 24: Tab 10.
3. Johnson CP, Myers SM; American Academy of Pediatrics Council on Children with Disabilities. Identification and evaluation of children with autism spectrum disorders. Pediatrics. 2007; 120(5):1183-1215.
4. Manning M, Hudgins L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med. 2010; 12(11):742-745.  
5. Manning M, Hudgins L. Use of array-based technology in the practice of medical genetics. Genet Med. 2007; 9(9):650-653.
6. 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(5):749-764.
7. Moeschler JB, Shevell M; American Academy of Pediatrics Committee on Genetics. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. 2006; 117(6):2304-2316.
8. Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Genet Med. 2008; 10(4):301-305.

1. Center for Disease Control and Prevention (CDC). Autism Spectrum Disorders. For additional information visit the CDC website: www.cdc.gov.  Accessed on June 30, 2011.
2. Center for Disease Control and Prevention (CDC). Developmental Disabilities.  For additional information visit the CDC website: www.cdc.gov. Accessed on June 30, 2011.

Array comparative genomic hybridization (aCGH)Chro
mosomal microarray analysis (CMA),
Comparative genomic hybridization (CGH) microarray
Cytogenetic microarray (CMA)
G-banded karyotyping
Microarray-based comparative genomic hybridization