Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
DESCRIPTION
Hereditary neuropathies are a heterogeneous group of disorders that may be inherited in an autosomal dominant, autosomal recessive, or X-linked dominant manner. These disorders can generally be diagnosed based on clinical presentation, nerve conduction studies, and family history. The most common type of hereditary motor and sensory neuropathy is Charcot-Marie-Tooth (CMT) disorder. CMT is characterized by chronic motor and sensory polyneuropathy resulting in weakness and atrophy of the muscles in the feet and/or hands. This is expressed as weak ankle dorsiflexion, depressed tendon reflexes, and pes cavus foot deformity (i.e., high arched feet). CMT needs to be distinguished from systemic disorders with neuropathy, other types of hereditary neuropathy, distal myopathies, hereditary sensory neuropathies and acquired disorders. Genetic testing has been proposed as a method to establish a specific diagnosis which aids in understanding the prognosis and risk assessment for family members. The majority of CMT cases are related to the PMP22 gene; however, there are more than 80 genes associated with CMT. The more common genes affected include the following:
DNM2 |
GJB1 |
MPZ |
RAB7A |
EGR2 |
HSPB1 |
MTMR2 |
SBF2 |
FGD4 |
HSPB8 |
NDRG1 |
SH3TC2 |
FIG4 |
LITAF |
NEFL |
TRPV4 |
GARS |
LMNA |
PMP22 |
YARS |
GDAP1 |
MFN2 |
PRX |
|
POLICY
Genetic testing for inherited peripheral neuropathy is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Genetic testing for inherited peripheral neuropathy for all other indications is considered investigational.
MEDICAL APPROPRIATENESS
Genetic testing for inherited peripheral neuropathy (e.g., Charcot-Marie-Tooth) is considered medically appropriate if ANY ONE of the following are met:
Known familial mutation (first or second degree relative) and ALL of the following:
Requested testing is ANY ONE of the following:
Single gene analysis
Deletion/Duplication analysis
Documentation of ANY ONE of the following:
Predisposition testing for presymptomatic or asymptomatic individual 18 years or older
Symptomatic individual with ANY ONE of the following:
Distal muscle weakness and atrophy
Weak ankle dorsiflexion (e.g., foot drop)
Distal sensory loss
Depressed or absent tendon reflexes
Foot deformity (e.g., high arches, hammer toes, pes cavus)
Electrodiagnostic studies consistent with a peripheral neuropathy
No known familial mutation related to inherited peripheral neuropathy and ALL of the following:
Acquired causes of peripheral neuropathy (e.g., diabetic neuropathy, vitamin B12 deficiency, chronic inflammatory demyelinating polyneuropathy, known mutation) have been excluded by standard diagnostic evaluation
Documentation of ANY ONE of the following:
Distal muscle weakness and atrophy
Weak ankle dorsiflexion (e.g., foot drop)
Distal sensory loss
Depressed or absent tendon reflexes
Foot deformity (e.g., high arches, hammer toes, pes cavus)
Genetic testing requested is ANY ONE of the following
Single gene
Multi-gene panel when ANY ONE of the following is met:
Electrodiagnostic studies are consistent with an axonal neuropathy or combined axonal and demyelinating neuropathy
Electrodiagnostic studies are consistent with a primary demyelinating neuropathy and PMP22 deletion/duplication analysis was completed and negative
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
ADDITIONAL INFORMATION
Molecular genetic testing can be used to establish a specific diagnosis which aids in understanding the prognosis and risk assessment for family members.
SOURCES
American Academy of Neurology. (2009, reaffirmed January 2022). Practice parameter: Evaluation of distal symmetric polyneuropathy: Role of laboratory and genetic testing (an evidence-based review). Retrieved January 19, 2023 from https://www.aan.com/Guidelines/home/GuidelineDetail/315.
Antoniadi, T., Buxton, C., Davis, G., Forrester, N., Smith, D., Lunt, P., & Burton-Jones, S. (2015). Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability. BMC Medical Genetics, 16, 84. (Level 4 evidence)
Bacquet, J., Stojkovic, T., Boyer, A., Martini, N., Audic, F., Chbrol, B., et al. (2018). Molecular diagnosis of inherited peripheral neuropathies by targeted next-generation sequencing: molecular spectrum delineation. BMJ Open, 8, e021632, doi: 10.1136/bmjopen-2018-021632. (Level 4 evidence)
BlueCross BlueShield Association. Evidence Positioning System. (2:2024). Genetic testing for the diagnosis of inherited peripheral neuropathies (2.04.89). Retrieved March 13, 2024 from www.bcbsaoca.com/eps/. (32 articles and/or guidelines reviewed)
Burgunder, J. M., Schols, L., Baets, J., Andersen, P., Gasser, T., Szolnoki, Z., et al. (2011). EFNS guidelines for the molecular diagnosis of neurogenetic disorders: Motoneuron, peripheral nerve and muscle disorders. European Journal of Neurology, 18 (2), 207-217. (Level 2 evidence)
Cornett, K., Menezes, M., Bray, P., Halaki, M., Shy, R., Yum, S., et al. (2016). Phenotypic variability of childhood Charcot-Marie-Tooth disease. Journal of American Medical Association, 73 (6), 645-651. (Level 4 evidence)
DiVincenzo, C., Elzinga, C., Medeiros, A., Karbassi, I., Jones, J., Evans, M., et al. (2014). The allelic spectrum of Charcot–Marie–Tooth disease in over 17,000 individuals with neuropathy. Molecular Genetics & Genomic Medicine, 2 (6), 522–529. (Level 2 evidence)
Dohrn, M.F., Glöckle, N., Mulahasanovic, L., Heller, C., Mohr, J., Bauer, C., et al. (2017). Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. Journal of Neurochemistry, 143 (5), 507-522. (Level 4 evidence)
eviCore healthcare. (2024, July). Clinical Guidelines. Lab Management Program. Charcot-Marie-Tooth neuropathy testing. Retrieved March 13, 2024 from www.evicore.com. (7 articles and/or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 12/14/2013
MOST RECENT REVIEW DATE: 4/11/2024
ID_EC
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
This document has been classified as public information.