Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Central Nervous System/Neuromuscular Disorder. 
Treatment: Genetic Testing. 
The insurer denied: Genetic Testing: Exome Sequence Analysis/WES-Whole Exome Sequencing. 
The denial is overturned in whole. 

The patient is a male with developmental delay, laryngomalacia, and episodic hyperkinetic movement disorder resembling choreiform movements. His symptoms are progressing in frequency. His provider feels that an inherited syndrome is highly likely; however, his genetic testing performed thus far as not revealed a diagnosis. He has also had lab work including thyroid stimulating hormone (TSH), free T4, alpha-fetoprotein (AFP), very long chain fatty acids (VLCFA), Lactate/pyruvate, ammonia, and creatinine kinase that have all been non-diagnostic. Magnetic resonance imaging (MRI) of his brain was normal and also did not reveal a diagnosis. He has also had an electroencephalogram (EEG) capturing these movements, which was normal, ruling out seizures. Family history includes a maternal grandfather with hypertrophic cardiomyopathy. His current treatment includes Gabapentin that initially helped, but did not sustain effectiveness, and Tetrabenazine, which has had no definite benefit. Prior treatments include Oxcarbazepine which was not helpful. The subject under review is whether the proposed genetic testing is likely to be more beneficial for this patient than any standard treatment.

The health plan's determination is overturned.

Whole exome sequencing (WES) is likely to be more beneficial than any standard treatment or treatments for this member. This patient does not yet have an underlying diagnosis for his abnormal movements, thus there is no standard treatment. WES is not considered inappropriate in this case. There are multiple studies in the medical literature that indicate WES testing has significant diagnostic yield that results in more effective treatment approaches.
To illustrate this point: The American College of Medical Genetics and Genomics recommends that exome sequencing is an appropriate test for patients for whom a genetic etiology is suspected but either the patient's phenotype is not consistent with a specific disorder that has more targeted genetic testing currently available, the testing currently available for the patient's phenotype has failed to arrive at a diagnosis, or the suspected genetic condition is associated with a high degree of genetic heterogeneity. For this patient, this statement holds true as his condition is not consistent with a specific disorder and prior testing including lab work, imaging, and an EEG has not revealed a diagnosis.
In addition, Exome sequencing has been shown to lead to direct changes in medical management, including changes to medications, surgical interventions, surveillance regimens, or preventative measures in approximately (~) 9-19% of patients and the majority of these interventions would be indicated in childhood.
For this patient, it is imperative that an accurate diagnosis be established to help guide medical management, screening and avoidance of medications that could worsen the member's condition or unnecessary, possibly invasive testing. Without finding a diagnosis, this patient may be subject to increased morbidity and even early mortality.