Appeal type: Experimental/Investigational
Decision: Upheld

Nature of Statutory Criteria/Case Summary: An enrollee has requested authorization and coverage for full exome sequencing (genetic test) services. Findings:  The physician reviewer found that American College of Medical Genetics and Genomics (ACMG) states, Major advances in DNA sequencing technology have made it possible to do large-scale sequencing, up to and including whole-genome sequencing, in an effort to identify a gene mutation that may provide a diagnosis for a patient with an abnormal phenotype. The ACMG definitions note, Whole-genome sequencing (WGS) implies the determination of the sequence of most of the DNA content comprising the entire genome of an individualThe exome is the component of the genome that predominantly encodes protein. The exome comprises about 1% of the genome and is the component most likely to include interpretable mutations that result in clinical phenotypes. Whole exome sequencing (WES) involves determination of the DNA sequence of most of these protein-encoding exons and may include some DNA regions that encode RNA molecules that are not involved in protein synthesis. According to the ACMG indications for diagnostic testing, 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. (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. Lidstone and colleagues describe functional movement disorder (FMD) as a subtype of functional neurological symptom disorder in which the primary symptom is tremor, dystonia, gait disorder, or other abnormal movement. The authors note, Patients with FMD have neurologic symptoms that are incongruent with known neurologic disease but are nevertheless genuine and cause distress and/or psychosocial impairment. The authors further note, Functional tremor is the most common type of FMD Functional tremor typically occurs with rest, posture, and action. Any body part may be involved, but hand tremor, leg tremor, and whole-body tremor are common sites. There are numerous positive signs of functional tremor, including the hallmark signs of distractibility and variability. The authors further note that functional gait disorders may occur, including astasia-abasia, astasia, and abasia. In this case, the patient presents with a complex medical history with multiple diagnoses, and genomic testing by whole exome sequencing was recommended due to the patients cognitive decline and worsening ambulatory capability, with presentation and course suggestive of a primary neurogenetic cause. However, this patient does not meet the ACMG indications for diagnostic testing, as the records do not note a phenotype or family history data indicating a genetic cause, and as the patient does not present with a defined genetic disorder. Neurological evaluations have documented multiple neurologic symptoms, and symptoms consistent with FMD on examination, without diagnostic evidence to suggest an organic central nervous system disorder. Therefore, full exome sequencing (genetic test) services is not likely to be more beneficial for evaluation of the patients condition than any available standard therapy.Findings:  Two of the three physician reviewers found the requested full exome sequencing (genetic test) services is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy.Final Result: The reviewers determined that the requested service is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. Therefore, the Health Plans denial should be upheld. Credentials/Qualifications: Physician reviewer 1 is board certified in clinical genetics and genomics and is actively practicing. Physician reviewer 2 is board certified in neurology and is actively practicing. Physician reviewer 3 is board certified in clinical genetics and genomics and in clinical biochemical genetics and is actively practicing. The reviewers are experts in the treatment of the enrollees medical condition and knowledgeable about the proposed treatment through recent or current actual clinical experience treating those with the same or a similar medical condition.