CPT 81228, 81229, S3870 - Chromosomal microarray analysis

Coding   Code Description CPT

81228 Cytogenetic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (eg, Bacterial Artificial Chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis)

81229 Cytogenetic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities

HCPCS
S3870 Comparative genomic hybridization (CGH) microarray testing for developmental delay, autism spectrum disorder and/or mental retardation



Genetic Testing for Developmental Delay/Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies


Introduction

Chromosomal microarray analysis (CMA) is one way of testing chromosomes. It focuses on parts of a chromosome that are too small to see with a microscope. CMA can detect small areas of extra or missing parts of a chromosome. CMA can find genetic changes that are connected to developmental disabilities. This policy describes when CMA may be covered for developmental delay, or intellectual disability, autism spectrum disorder, or certain other types of health problems called congenital anomalies. This policy also discusses next-generation sequencing. This type of genetic testing can look at millions of DNA strands all at once. Next-generation sequencing produces a lot of information, but it’s unknown how all of this information relates to developmental delay. For this reason next-generation sequencing is considered unproven for developmental delay, intellectual disability, autism spectrum disorders, or congenital anomalies.

Note:   The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered. 
Policy Coverage Criteria   type of Testing Medical Necessity  hromosomal microarray nalysis (CMA)

Chromosomal microarray analysis (CMA) may be considered medically necessary as first-line testing in the initial evaluation (see Additional Information) of individuals with any one of the following: * Apparent nonsyndromic developmental delay/intellectual
disability OR * Autism spectrum disorder OR * Two or more congenital anomalies not specific to a well- delineated genetic syndrome  Chromosomal microarray analysis (CMA) is considered investigational for the evaluation of all other conditions of delayed development, including but not limited to idiopathic growth or language delay.
ype of Testing Investigational

Next-generation equencing panels

Additional Information

Panel testing using next-generation sequencing is considered investigational in all cases of suspected genetic abnormality in children with developmental delay/intellectual disability, autism spectrum disorder, or congenital anomalies.

Use of CMA testing as outlined in this policy is not intended for use in the prenatal period. A 2013 guidelines update from American College of Medical Genetics (Schaefer et al, 2013)


Additional Information

stated that a stepwise (or tiered) approach to the clinical genetic diagnostic evaluation of autism spectrum disorder is recommended, with the recommendation being for first tier to include fragile X syndrome and chromosomal microarray (CMA) testing.

* Recommendations from the 2010 American College of Medical Genetics guidelines (Manning et al 2010) on array-based technologies and their clinical utilization for detecting chromosomal abnormalities include the following: “Appropriate follow-up is recommended in cases of chromosome imbalance identified by CMA, to include cytogenetic/FISH studies of the patient, parental evaluation, and clinical genetic evaluation and counseling.”

* In some cases of CMA analysis, the laboratory performing the test confirms all reported copy number variants with an alternative technology, such as fluorescent in situ hybridization analysis.

Related Information 


Definition of Terms

Malformation: Defects of organs or body parts due to an intrinsically abnormal developmental process. In this process, a structure is not formed, is partially formed, or is formed in an abnormal fashion.

Major malformation: A structural defect that has a significant effect on function or social acceptability. These often require surgical repair. Example: ventricular septal defect or a neural tube defect such as meningomyelocele or cleft lip.
Minor malformation: A structural abnormality that has minimal effect on function or societal acceptance. They rarely are medically significant or require surgical intervention. Examples: preauricular ear pit or partial syndactyly (fusion) of the second and third toes. 

Syndrome: A recognizable pattern of multiple malformations. Syndrome diagnoses are often relatively straightforward and common enough to be clinically recognized without specialized testing. Examples include Down syndrome and achondroplasia. However, in the very young, or in the case of syndromes with variable presentation, confident identification may be difficult without additional testing.


Consideration of Age

The age range described in this policy considers chromosomal microarray analysis testing in infants and children to be medically necessary for characteristics of developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), and/or congenital anomalies. Coverage is based on published guidelines by the American College of Medical Genetics and the American Academy of Neurology. This testing can detect genetic imbalances in infants or children with the stated characteristics and therefore provide opportunities to impact clinical management decisions.

Genetic Counseling

Genetic counseling is primarily aimed at patients who are at risk for inherited disorders, and experts recommend formal genetic counseling in most cases when genetic testing for an inherited condition is considered. The interpretation of the results of genetic tests and the understanding of risk factors can be very difficult and complex. Therefore, genetic counseling will assist individuals in understanding the possible benefits and harms of genetic testing, including the possible impact of the information on the individual’s  family. Genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by  an individual with experience and expertise in genetic medicine and genetic testing methods.

Evidence Review 

Description
Chromosomal microarray analysis (CMA) testing has been proposed for detection of genetic imbalances in infants or children with characteristics of developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), and/or congenital anomalies. CMA testing increases the diagnostic yield over karyotyping in children with the aforementioned characteristics, and CMA testing may impact clinical management decisions. Next-generation sequencing (NGS) panel testing allows for simultaneous analysis of a large number of genes and, in patients with normal CMA testing, the next-generation testing has been proposed as a way to identify single-gene causes of syndromes that have autism as a significant clinical feature. Use of Common Genetic Variants (Single Nucleotide Variants) to Predict Risk of Non-familial Breast Cancer