Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Developmental Delay
Treatment: Genetic Testing
The insurer denied the genetic testing.
The health plan's determination is overturned.

The patient is a female with developmental delays, feeding difficulties and other symptoms suggestive of underlying genetic syndrome or disorder. Despite extensive clinical genetic evaluations and multiple genetic tests, a definitive diagnosis has not been established. The provider ordered Whole exome sequencing test (WES) and the Insurer is questioning the medical necessity of the requested test.

The proposed health service or treatment of genetic diagnostic testing is likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease. The whole exome sequencing (WES) test analyzes the protein coding portion of the human genome and is offered by a number of CLIA-certified diagnostic laboratories. WES does not need Food and Drug Administration (FDA) approval as it is a genetic test based on routine molecular techniques, such as deoxyribonucleic acid (DNA) isolation, enrichment, polymerase chain reaction (PCR), and DNA sequencing. The results of the tests will likely identify the underlying genetic causes of this member's disorder and may offer an opportunity for targeted treatment. Furthermore, WES is in a wide use by clinical geneticists and is current standard of care for patients with similar complex genetic syndromes of unknown causes. Despite extensive genetic clinical and molecular evaluations no definitive diagnosis was established for this patient. The disease is presumed to have genetic etiology based on the clinical symptoms. The WES has the potential to identify a mutation a gene responsible for this member's disease. Recent recommendations by the American College of Medical Genetics (see http://www.acmg.net/StaticContent/PPG/Clinical_Application_of_Genomic_Sequencing.pdf) determines the indications for exome sequencing that are listed below: " Indications for Diagnostic Testing 1. WGS /WES should be considered in the clinical diagnostic assessment of a phenotypically affected individual when:
a. The phenotype or family history data strongly implicate a genetic etiology, but the phenotype does not correspond with a specific disorder for which a genetic test targeting a specific gene is available on a clinical basis (as in the case of this member), 
b. A patient presents with a defined genetic disorder that demonstrates a high degree of genetic heterogeneity, making WES or WGS analysis of multiple genes simultaneously a more practical approach,
c. A patient presents with a likely genetic disorder but specific genetic tests available for that phenotype have failed to arrive at a diagnosis (this is also the case of this member),
d. A fetus with a likely genetic disorder in which specific genetic tests, including targeted sequencing tests, available for that phenotype have failed to arrive at a diagnosis.
Recent developments in high-throughput sequence capture methods and next-generation sequencing technologies have now made WES a viable approach that has become a standard of care in order to elucidate the genetic basis of Mendelian disorders with hitherto unknown etiology. Currently, there is compelling evidence that exome sequencing is an efficient and direct diagnostic tool for identifying the causes of complex and genetically heterogeneous neurodegenerative diseases, early-stage disease or cases with limited clinical data. The diagnostic yield for finding a causative deleterious gene mutation using WES ranges from around 20 percent (%) to 30% in patients in whom biochemical, chromosomal, microarray, metabolic, and targeted gene sequencing studies have yielded normal or equivocal results. Based on these facts the requested WES test can be justified as medically necessary.