BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for the Diagnosis of Inherited Peripheral Neuropathies

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

MEDICAL APPROPRIATENESS

 

IMPORTANT REMINDERS

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. (2013). The role of laboratory and genetic testing in diagnosing distal symmetric polyneuropathy. Retrieved May 8, 2020 from https://www.aan.com/Guidelines/home/GetGuidelineContent/322.

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.

BlueCross BlueShield Association. Evidence Positioning System. (2:2021). Genetic testing for the diagnosis of inherited peripheral neuropathies (2.04.89). Retrieved February 25, 2021 from https://www.evidencepositioningsystem.com/.  (30 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.

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. Abstract retrieved June 21, 2019 from PubMed database.

eviCore healthcare. (2021, January). Clinical Guidelines. Lab Management Program. Charcot-Marie-Tooth neuropathy testing. Retrieved February 25, 2021 from www.evicore.com. (7 articles and/or guidelines reviewed)

ORIGINAL EFFECTIVE DATE:  12/14/2013

MOST RECENT REVIEW DATE:  4/8/2021

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.