HumanaCommercial Clinical Policy

Humana Comparative Genomic Hybridization/Chromosomal Microarray Form


Comparative Genomic Hybridization/Chromosomal Microarray (CGH/CMA)

Notes: For details on more generalized conditions and approved indications for CGH/CMA or specific state mandates, please refer to the medical coverage policy or consult the member’s individual certificate.

Indications

(266966) Is the CGH/CMA being performed to confirm a diagnosis that can be routinely diagnosed by clinical evaluation alone? 
(266967) Is the CGH/CMA being performed for the detection of deletions/duplications for single gene disorders such as BRCA, CFTR, DMD, MECP2, PTEN? 
(266968) Is the indication for CGH/CMA related to advanced maternal age only? 
(266969) Is the CGH/CMA being requested for the evaluation of recurrent pregnancy loss? 
(266970) Are any of the following soft markers present without accompanying fetal structural anomalies: Absent nasal bone, choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, pyelectasis, shortened long bones? 

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Effective Date

09/28/2023

Last Reviewed

NA

Original Document

  Reference



Description

Comparative genomic hybridization (CGH) (also known as array CGH [aCGH]) is a laboratory method to aid in the detection of extra (duplicated) or missing (deleted) chromosomal segments, often referred to as copy number variants (CNVs). CGH may also be referred to as chromosomal microarray analysis (CMA).

CGH is a microchip-based test that provides analysis of many pieces of deoxyribonucleic acid (DNA). The technique works by comparing the DNA content of an individual undergoing testing to that of a reference sample. A difference between the two samples indicates a variant. aCGH offers a higher resolution than conventional CGH.

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023
Revision Date: 09/28/2023
Review Date: 09/28/2023
Policy Number: HUM-0515-018

Page: 1 of 28

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Two common microarray platforms include oligonucleotide (oligos) and single nucleotide polymorphism (SNP) arrays. Oligonucleotides are short single strands of chemically synthesized (laboratory-made) DNA or RNA. SNP arrays are used to detect DNA variations that occur when a single nucleotide (adenine, thymine, cytosine or guanine) in the genome sequence is altered.

The design of microarrays include whole genome and targeted arrays. Whole genome arrays cover the entire human genome while targeted arrays analyze specific regions of the genome.

CGH can be used for a variety of indications including, but may not be limited to, the evaluation of autism spectrum disorder (ASD), hematologic malignancies, hereditary myeloid malignancy predisposition syndromes (HMMPS), global developmental delay (GDD), intellectual disability (ID) (eg, intellectual development disorder), melanoma, microcephaly, microdeletion/microduplication syndromes, multiple congenital anomalies, pregnancy loss and prenatal assessment of fetal structural anomalies.

FMR1 gene testing for fragile X syndrome is often ordered adjunctively with CGH for the evaluation of individuals diagnosed with ASD, GDD or ID. For information regarding gene testing for fragile X syndrome, please refer to Genetic Testing for Diagnosis of Noncancer Indications Medical Coverage Policy.

CGH has been suggested for preimplantation genetic testing for aneuploidy (PGT-A). For information regarding PGT-A, please refer to Preimplantation Genetic Testing Medical Coverage Policy.

For information regarding genetic testing for the following, please refer to Genetic Testing Medical Coverage Policy:

  • DNA banking or preservation
  • General population screening
  • Individual 17 years of age or younger for adult-onset conditions
  • Interpretation and reporting for molecular pathology procedure
  • Polygenic risk score (PRS) and single nucleotide polymorphisms (SNPs)
  • Repeat germline or somatic genetic testing
  • Retrieved archival tissue

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Page: 3 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Humana recognizes that the field of genetic testing is rapidly changing and that other tests may become available.

Coverage Determination

Pregnancy Loss and Prenatal Indications

Any state mandates for CGH/CMA take precedence over this medical coverage policy.

Genetic testing may be excluded by certificate. Please consult the member’s individual certificate regarding Plan coverage.

Apply General Criteria for Genetic and Pharmacogenomics Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding general criteria for genetic tests, please refer to Genetic Testing Medical Coverage Policy.

Humana member may be eligible under the Plan for CGH/CMA for the following pregnancy loss and prenatal indications when criteria are met:

  • Evaluation of fetal tissue (amniotic fluid, placenta or products of conception) for intrauterine fetal demise or stillbirth when karyotype has been performed and a specific cause cannot be determined (If viable tissue is not available, karyotype prior to CGH/CMA is not required); OR
  • Evaluation of one or more major fetal structural anomalies (which include brain abnormalities, cleft lip and/or palate and heart defects) detected on prenatal ultrasound. If a structural abnormality is strongly suggestive of a particular aneuploidy in the fetus (eg, duodenal atresia which is characteristic of trisomy 21), karyotype with or without fluorescence in situ hybridization (FISH) is indicated prior to CGH/CMA; OR
  • Noninvasive prenatal screening (NIPS) using cfDNA for any of the following:
    • No-call result due to low fetal fraction if maternal blood for NIPS was drawn at an appropriate gestational age; OR
    • Positive for microdeletions and/or microduplications or smaller copy-number change

Maternal cell contamination (MCC) studies (81265) is considered integral to the primary procedure and not separately reimbursable.

Coverage Limitations

Humana members may NOT be eligible under the Plan for CGH/CMA for any pregnancy loss and prenatal indication other than those listed above including, but may not be limited to:

  • Confirmation of diagnosis of a syndrome that can be routinely diagnosed by clinical evaluation alone
  • Detection of deletions/duplications and/or gene or genomic sequencing for single gene disorders (eg, BRCA, CFTR, DMD, MECP2, PTEN)
  • Evaluation of any of the following indications:
    • Advanced maternal age only
    • Pregnancy losses by parental blood samples
    • Recurrent pregnancy loss
  • Any of the following soft markers:
    • Absent nasal bone
    • Choroid plexus cysts
    • Echogenic bowel
    • Echogenic intracardiac focus
    • Pyelectasis
    • Shortened long bones (eg, femur, humerus)
  • Evaluation of the following without the presence of fetal structural anomalies:
    • Abnormal serum screening
    • Hydrops fetalis
    • Nuchal translucency

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023

Revision Date: 09/28/2023

Review Date: 09/28/2023

Policy Number: HUM-0515-018

Page: 4 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023

Revision Date: 09/28/2023

Review Date: 09/28/2023

Policy Number: HUM-0515-018

Page: 5 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Prenatal invasive diagnostic genetic testing

  • NIPS using cfDNA is positive for T13, T18, T21, sex chromosome aneuploidy (SCA), other aneuoploidy, triploidy and karyotype confirmed results
  • Known family history of chromosomal rearrangement

These are considered experimental/investigational as they are not identified as widely used and generally accepted for any other proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Coverage Pediatric and Postnatal Indications

Pediatric and Postnatal Indications

Any state mandates for CGH/CMA take precedence over this medical coverage policy.

Coverage Determination

Genetic testing may be excluded by certificate. Please consult the member’s individual certificate regarding Plan coverage.

Apply General Criteria for Genetic and Pharmacogenomics Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding general criteria for genetic tests, please refer to Genetic Testing Medical Coverage Policy.

Humana members may be eligible under the Plan for CGH/CMA (eg, 0209U) for the following pediatric and postnatal indications when criteria are met:

  • At least one major congenital anomaly (eg, brain abnormalities, cleft lip and/or palate and heart defects); OR
  • ASD in an individual who exhibits developmental delays or persistent deficits in social communication and social interaction across multiple contexts (see testing strategy for adjunctive fragile X gene testing)*; OR
  • NIPS using cell-free DNA (cfDNA) is positive for trisomy 13 (T13), trisomy 18 (T18), trisomy 21 (T21), other aneuploidy or triploidy; AND

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023
Revision Date: 09/28/2023
Review Date: 09/28/2023
Policy Number: HUM-0515-018

Page: 6 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

  • Neonatal physical examination indicates abnormal clinical phenotype; AND
  • Cytogenetic analysis (eg, fluorescence in situ hybridization (FISH) or karyotype) is normal; OR
  • NIPS using cfDNA is positive for smaller copy-number changes; OR
  • Unexplained significant GDD (see Coverage Limitation section regarding developmental delay [DD]) (see testing strategy for adjunctive fragile X syndrome gene testing)*; AND
  • Delays of six months or more in two or more developmental areas (domains).

Developmental domains include: cognitive skills, social and emotional skills, speech and language skills, fine and gross motor skills and activities of daily living; OR

  • Unexplained ID (see testing strategy for adjunctive fragile X syndrome gene testing)*; AND
    • Limitations of adaptive functioning affecting at least one of three domains: conceptual, practical, social; AND
    • Limitations of intellectual functioning (eg, abstract thinking, judgment, learning, problem solving, reasoning); AND
    • No family history of chromosomal rearrangement or recurrent pregnancy loss; OR
  • Microcephaly in an individual 5 years of age or younger; AND
    • Occipitofrontal circumference (OFC or head circumference) greater than two standard deviations (SD) below the mean (less than 3rd percentile) for age and sex determined by a standardized head circumference chart (eg, Centers for Disease Control and Prevention [CDC], World Health Organization [WHO]); OR
  • Serial OFC measurements demonstrate progressive decrease in head size (downward crossing of at least two major percentiles [eg, 90th, 75th, 25th, 10th]) for age and sex determined by a standardized head circumference chart (eg, CDC, WHO) between health supervision visits; OR
  • Microdeletion or microduplication syndromes (eg, DiGeorge syndrome, Kleefstra syndrome) (for information regarding coverage determination/limitations for Angelman and Prader-Willi syndromes, please refer to Genetic Testing for Angelman and Prader-Willi Syndromes Medical Coverage Policy); AND
    • Individual to be tested presents with clinical findings suggestive of a known microdeletion or microduplication syndrome and FISH is normal; OR
    • Individual to be tested has a first-degree relative with a known microdeletion or microduplication syndrome that is too small to be detected by FISH

*Testing strategy: FMR1 gene testing for fragile X syndrome may be ordered adjunctively with CMA for ASD, GDD or ID if criteria for fragile X syndrome testing are met. For information regarding coverage determination/limitations for fragile X syndrome, please refer to Genetic Testing for Diagnosis of Noncancer Indications Medical Coverage Policy.

Coverage Limitations

Humana members may NOT be eligible under the Plan for CGH/CMA for pediatric or postnatal indications other than those listed above including, but may not be limited to:

  • Confirmation of diagnosis of a syndrome that can be routinely diagnosed by clinical evaluation alone
  • Detection of deletions/duplications and/or gene or genomic sequencing for single gene disorders (eg, BRCA, CFTR, DMD, MECP2, PTEN)
  • Evaluation of any of the following indications when not part of a more generalized condition (ASD, GDD or ID):
    • Delayed puberty

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023
Revision Date: 09/28/2023
Review Date: 09/28/2023
Policy Number: HUM-0515-018

Page: 7 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023
Revision Date: 09/28/2023
Review Date: 09/28/2023
Policy Number: HUM-0515-018

Page: 8 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

  • Epilepsy
  • Hearing loss
  • Hypogonadism
  • Klinefelter syndrome
  • Language delay
  • Turner syndrome

Known family history of chromosomal rearrangement

NIPS using cfDNA is positive for T13, T18, T21, sex chromosome aneuploidy (SCA), other aneuoploidy, triploidy and neonatal physical exam indicates normal clinical phenotype

These are considered experimental/investigational as they are not identified as widely used and generally accepted for any other proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Humana members may NOT be eligible under the Plan for CGH/CMA for developmental delay (DD). This is considered not medically necessary as defined in the member's individual certificate. Please refer to the member's individual certificate for the specific definition.

Coverage Determination

Cancer

Any state mandates for CGH/CMA take precedence over this medical coverage policy.

Genetic testing may be excluded by certificate. Please consult the member's individual certificate regarding Plan coverage.

Apply General Criteria for Genetic and Pharmacogenomics Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding general criteria for genetic tests, please refer to Genetic Testing Medical Coverage Policy.

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023

Revision Date: 09/28/2023

Review Date: 09/28/2023

Policy Number: HUM-0515-018

Page: 9 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Humana members may be eligible under the Plan for CGH/CMA for the evaluation of the following cancer indications when criteria are met:

  • Acute lymphoblastic leukemia (ALL) (adult and pediatric) in cases of aneuploidy or failed karyotype (chromosome analysis); OR
  • HMMPS when any of the following indications are present:
    • Allogeneic sibling donor is a hematopoietic stem cell transplant (HSCT) candidate when HSCT recipient is diagnosed with acute leukemia or myelodysplastic syndrome (MDS); OR
    • Personal history of any of the following:
      • Acute myeloid leukemia (AML) or MDS diagnosed before 50 years of age; OR
      • Aplastic anemia; OR
      • Congenital limb anomalies (eg, especially thumb/forearm); OR
      • Hypocellular MDS; OR
      • Immune deficiencies (eg, B lymphopenia, monocytopenia); OR
      • Monosomy 7 and 30 years of age or younger; OR
      • Multiple cancers, two or more; OR
      • Primary fibrosis; OR
      • Severe and/or recurrent infections (eg, atypical mycobacterial, fungal or viral infections); OR
    • First-degree relative diagnosed with any of the following:
      • Acute leukemia; OR

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023

Revision Date: 09/28/2023

Review Date: 09/28/2023

Policy Number: HUM-0515-018

Page: 10 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

  • Bone marrow failure; OR
  • Congenital limb anomalies (especially thumb/forearm); OR
  • Early-onset malignancy; OR
  • Excessive toxicity with chemotherapy or radiation; OR
  • Genetically defined inherited bone marrow failure/acute leukemia/MDS predisposition syndrome; OR
  • Hypocellular marrow; OR
  • Macrocytosis; OR
  • MDS; OR
  • Poor stem cell mobilizer; OR
  • Pulmonary fibrosis; OR
  • Severe and/or recurrent infections (eg, atypical mycobacterial, fungal or viral infections); OR
  • Unexplained cytopenia (eg, anemia, leukopenia and/or thrombocytopenia); AND
  • Concomitant diseases (eg, infection, nutritional deficiencies, medication use and alcohol consumption) have been ruled out as a source of cytopenia; AND
  • Routine tests** have not detected the source of cytopenia

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023
Revision Date: 09/28/2023
Review Date: 09/28/2023
Policy Number: HUM-0515-018

Page: 11 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Spitz Tumor

Humana members may be eligible under the Plan for CGH/CMA to evaluate atypical Spitz tumor to differentiate from melanoma when histological findings are equivocal. **Examples of routine tests to detect cytopenia include, but may not be limited to: complete blood count, platelet count, blood smear, prothrombin time, partial thromboplastin time and/or basic or comprehensive metabolic panel. Refer to reference intervals provided by laboratory.

Coverage Limitations

Humana members may NOT be eligible under the Plan for CGH/CMA for any cancer indications other than those listed above including, but may not be limited to:

  • Detection of deletions/duplications and/or gene or genomic sequencing for single gene disorders (eg, BRCA, CFTR, DMD, MECP2, PTEN)
  • Evaluation of the following malignancies:
    • Chronic lymphoblastic (lymphocytic) leukemia (CLL)
    • Melanoma
    • Multiple myeloma

These are considered experimental/investigational as they are not identified as widely used and generally accepted for any other proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Background

Additional information about autism, fetal demise, global developmental delay, intellectual disability, leukemia or melanoma may be found from the following websites:

  • American Academy of Dermatology
  • American Academy of Neurology
  • American Academy of Pediatrics
  • American Association on Intellectual and Developmental Disabilities

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023
Revision Date: 09/28/2023
Review Date: 09/28/2023
Policy Number: HUM-0515-018

Page: 12 of 28

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

American Cancer Society
Centers for Disease Control and Prevention
Genetics Home Reference
Leukemia & Lymphoma Society
National Library of Medicine
Society for Maternal-Fetal Medicine

Medical Alternatives

Alternatives to CGH/CMA for ASD, GDD and ID include, but may not be limited to, the following:

  • Analysis of single genes (please refer to Genetic Testing for Diagnosis of Noncancer Indications Medical Coverage Policy)
  • Brain imaging
  • FISH
  • Fragile X gene testing (please refer to Genetic Testing for Diagnosis of Noncancer Indications Medical Coverage Policy)
  • Karyotype (chromosome analysis)
  • Metabolic studies

Alternatives to CGH/CMA for congenital anomalies include, but may not be limited to:

  • Analysis of single genes (please refer to Genetic Testing for Diagnosis of Noncancer Indications Medical Coverage Policy)
  • FISH
  • Karyotype (chromosome analysis)

Alternatives to CGH/CMA for prenatal indications include, but may not be limited to:

Comparative Genomic Hybridization/Chromosomal Microarray Analysis

Effective Date: 09/28/2023

Revision Date: 09/28/2023

Review Date: 09/28/2023

Policy Number: HUM-0515-018

Page: 13 of 28