Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Limited neck mobility, environmental allergies, conductive hearing loss on the left accompanied by external ear abnormalities and some behavioral and attention issues, heart murmur, stage II chronic kidney disease
Treatment: Panel testing [XomeDxPlus Trio: Whole Exome
Sequencing (WES) with Mitochondrial Genome Sequencing and Deletion Analysis (genetic test, procedure code(s) 81415, 81416, 81460)
The insurer denied: Panel testing [XomeDxPlus Trio: Whole Exome Sequencing (WES) with Mitochondrial Genome Sequencing and Deletion Analysis (genetic test, procedure code(s) 81415, 81416, 81460)
The denial is overturned.

This patient is a school-aged male child that was referred to a genetics clinic due to concerns for a syndromic explanation for his limited neck mobility. He had already been evaluated by a number of physicians, one of whom suspected branchiootorenal syndrome. However, specific genetic testing (for SIX1 and EYA1) was reportedly normal. The patient has environmental allergies, conductive hearing loss on the left accompanied by external ear abnormalities and some behavioral and attention issues. Additionally, he has a heart murmur with a normal echocardiogram and one kidney with a reported history of urosepsis and stage II chronic kidney disease. The patient is followed by Urology and Nephrology.

The health plan should cover the proposed treatment of Panel testing [XomeDxPlus Trio: Whole Exome Sequencing (WES) with Mitochondrial Genome Sequencing and Deletion Analysis (genetic test, procedure code(s) 81415, 81416, 81460).

The requested health service of Panel testing [XomeDxPlus Trio: Whole Exome Sequencing (WES) with Mitochondrial Genome Sequencing and Deletion Analysis (genetic test, procedure code(s) 81415, 81416, 81460) or treatment is considered medically appropriate and is more beneficial than any standard treatment for the patient's condition or disease. Clinical exome sequencing "is rapidly becoming the new standard for sequencing in genetic diagnostics, as all 21,000 genes in the human genome can be evaluated in an essentially unbiased manner." (1) When determining the appropriateness of genetic testing, the first essential step is clinical evaluation. In instances where phenotypic presentation does not yield a diagnosis, rather than embarking on a series of diagnostic tests, "exome sequencing could abbreviate or stop the diagnostic testing cascade by establishing the specific rare diagnosis genetically. A Pediatric Genomic Medicine group found that next-generation sequencing has the potential to truncate the diagnostic odyssey by 5 years." (1) Further, "exome sequencing results can alleviate family member concerns regarding potential risk of transmission or identify individuals in need of more specialized care or surveillance to reduce future disease complications." (1) According to clinical guidelines published by the American College of Medical Genetics (ACMG) and Genomics, "based on the SER [systemic evidence review] there is a strong recommendation based on the available evidence to support the use of ES/GS [exome sequencing/genome sequencing] as either a first- (or second-) line test in patients with CA/DD/ID [congenital anomalies or developmental delay or intellectual disability]." (3) Based on ACMG (American College of Medical Genetics) guidelines, this child meets requirements for whole genome sequencing: multiple anomalies not specific to a well-delineated genetic syndrome apparent before one year of age; results of testing would establish a clinical diagnosis that may lead to changes in management; and genetic counseling has been performed including all steps listed.