Genetic Testing for Limb-Girdle Muscular Dystrophies

POLICY NUMBER

L.2.04.459

DESCRIPTION

The limb-girdle muscular dystrophies are a genetically heterogeneous group of muscular dystrophies characterized by predominantly proximal muscle weakness (pelvic and shoulder girdles). A large number of genetic variants have been associated with limb-girdle muscular dystrophies.

Muscular Dystrophies

Muscular dystrophies are a group of inherited disorders characterized by progressive weakness and degeneration of skeletal muscle, cardiac muscle, or both, which may be associated with respiratory muscle involvement or dysphagia and dysarthria. Muscular dystrophies are associated with a wide spectrum of phenotypes, which may range from rapidly progressive weakness leading to death in the second or third decade of life to clinically asymptomatic disease with elevated creatine kinase (CK) levels. Muscular dystrophies have been classified by clinical presentation and genetic etiology. The most common are the dystrophinopathies, Duchenne and Becker muscular dystrophies, which are characterized by pathogenic variants in the dystrophin gene. Other muscular dystrophies are characterized by the location of onset of clinical weakness and include the limb-girdle muscular dystrophies, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, and humeroperoneal muscular dystrophy (also known as Emery-Dreifuss muscular dystrophy). Congenital muscular dystrophy is a genetically heterogeneous group of disorders, which historically included infants with hypotonia and weakness at birth and findings of muscular dystrophy on biopsy. Finally, myotonic dystrophy is a multisystem disorder characterized by skeletal muscle weakness and myotonia in association with cardiac abnormalities, cognitive impairment, endocrinopathies, and dysphagia.

Limb-Girdle Muscular Dystrophies

The term limb-girdle muscular dystrophy is a clinical descriptor for a group of muscular dystrophies characterized by predominantly proximal muscle weakness (pelvic and shoulder girdles) that may be included in the differential diagnosis of Duchenne muscular dystrophy and Becker muscular dystrophy. Onset can be in childhood or adulthood. The degree of disability depends on the location and degree of weakness. Some limb-girdle muscular dystrophy subtypes are characterized by only mild, slowly progressive weakness, while others are associated with early-onset, severe disease with loss of ambulation. Limb-girdle muscular dystrophies may be associated with cardiac dysfunction, cardiomyopathy (dilated or hypertrophic), respiratory depression, and dysphagia or dysarthria. Of particular note is the risk of cardiac complications, which is a feature of many but not all limb-girdle muscular dystrophies. Most patients have elevated creatine kinase (CK) levels.

Limb-girdle muscular dystrophies have an estimated prevalence ranging from 2.27 to 4 per 100,000 in the general population, constituting the fourth most prevalent muscular dystrophy type after the dystrophinopathies (Duchenne muscular dystrophy and Becker muscular dystrophy), facioscapulohumeral muscular dystrophy, and myotonic dystrophy. The prevalence of specific types increases in populations with founder pathogenic variants (eg, Finland, Brazil).

Genetic Basis and Clinical Correlation

As the genetic basis of the limb-girdle muscular dystrophies has been elucidated, it has been recognized that there is tremendous heterogeneity in genetic variants that cause the limb-girdle muscular dystrophy phenotype. Limb-girdle muscular dystrophies were initially classified based on a clinical and locus-based system. As of 2015, at least 9 autosomal dominant types (designated LGMD1A through LGMD1H) and at least 23 autosomal recessive types (designated LGMD2A through LGMD2W) have been identified. Subtypes vary in inheritance, pathophysiology, age of onset, and severity. The table below summarizes involved gene and protein, clinical characteristics (if known), and proportions of all cases represented by a specific genotype (if known).

Table 1: Summary of Genetic Basis of Limb-Girdle Muscular Dystrophy

AR: autosomal recessive; LGMD: limb-girdle muscular dystrophy. ª Rare recessive cases have been described for IB and IC.

The prevalence of different variants and limb-girdle muscular dystrophy subtypes can differ widely by country, but the autosomal recessive forms are generally more common. Pathogenic variants in CAPN3 represent 20% to 40% of limb-girdle muscular dystrophy cases, and LGMD2A is the most frequent limb-girdle muscular dystrophy in most countries. DYSF pathogenic variants leading to LGMD2B are the second most common limb-girdle dystrophy in many, but not all, areas (15-25%). Sarcoglycanopathies constitute about 10% to 15% of all limb-girdle muscular dystrophies, but 68% of the severe forms.

In an evaluation of 370 patients with suspected limb-girdle muscular dystrophy enrolled in a registry from 6 U.S. university centers, 312 of whom had muscle biopsy test results available, Moore and colleagues reported on the distribution of limb-girdle muscular dystrophy subtypes based on muscle biopsy results as follows: 12% LGMD2A; 18% LGMD2B; 15% LGMD2C-2F; and 1.5% LGMD1C.

Clinical Variability

Other than presentation with proximal muscle weakness, limb-girdle muscular dystrophy subtypes can have considerable clinical variability regarding weakness severity and associated clinical conditions. The sarcoglycanopathies (LGMD2C-2F) cause a clinical picture similar to that of the intermediate forms of Duchenne muscular dystrophy and Becker muscular dystrophy, with the risk of cardiomyopathy in all forms of the disease.

Of particular clinical importance is the fact that while most, but not all, limb-girdle muscular dystrophy subtypes are associated with an increased risk of cardiomyopathy, arrhythmia, or both, the risk of cardiac disorders varies across subtypes. LGMD1A, LGMD1B, LGMB2C-K, and LGMD2M-P have all been associated with cardiac involvement. Sarcoglycan variants tend to be associated with severe cardiomyopathy. Similarly, patients with the limb-girdle muscular dystrophy subtypes of LGMD2I and 2C-2F are at higher risk of respiratory failure.

Many genes associated with limb-girdle muscular dystrophy subtypes have allelic disorders, both with neuromuscular disorder phenotypes and clinically unrelated phenotypes. Variants in the lamin A/C proteins, which are caused by splice-site variants in the LMNA gene, are associated with different neuromuscular disorder phenotypes, including Emery-Dreifuss muscular dystrophy, a clinical syndrome characterized by childhood-onset elbow, posterior cervical, and ankle contractures and progressive humeroperoneal weakness, autosomal dominant limb-girdle muscular dystrophy (LGMD1B), and congenital muscular dystrophy. All forms have been associated with cardiac involvement, including atrial and ventricular arrhythmias and dilated cardiomyopathy.

Clinical Diagnosis

A diagnosis of limb-girdle muscular dystrophy is suspected in patients who have myopathy in the proximal musculature in the shoulder and pelvic girdles, but the distribution of weakness and the degree of involvement of distal muscles varies, particularly early in the disease course. Certain limb-girdle muscular dystrophy subtypes may be suspected by family history, patterns of weakness, CK levels, and associated clinical findings. However, there is considerable clinical heterogeneity and overlap across the limb-girdle muscular dystrophy subtypes.

Without genetic testing, diagnostic evaluation can typically lead to a general diagnosis of a limb-girdle muscular dystrophy, with limited ability to determine the subcategory. Most cases of limb-girdle muscular dystrophy will have elevated CK levels, with some variation in the degree of elevation based on subtype. Muscle imaging with computed tomography (CT) or magnetic resonance imaging may be obtained to assess areas of involvement and guide muscle biopsy. Magnetic resonance imaging or computed tomography may be used to evaluate patterns of muscle involvement. At least for calpainopathy (LGMD2A) and dysferlinopathy (LGMD2B), magnetic resonance imaging may show patterns distinct from other neuromuscular disorders, including hyaline body myopathy and myotonic dystrophy. In a study that evaluated muscle computed tomography in 118 patients with limb-girdle muscular dystrophy and 32 controls, there was generally poor overall interobserver agreement (κ=0.27), and low sensitivity (40%) and specificity (58%) for limb-girdle muscular dystrophy.

Electromyography has limited value in limb-girdle muscular dystrophy, although it may have clinical utility if there is a clinical concern for type III spinal muscular atrophy. Electromyography typically shows myopathic changes with small polyphasic potentials.

A muscle biopsy may be used in suspected limb-girdle muscular dystrophy to rule out other, treatable causes of weakness (in some cases), and to attempt to identify a limb-girdle muscular dystrophy subtype. All limb-girdle muscular dystrophy subtypes are characterized on muscle biopsy by dystrophic features, with degeneration and regeneration of muscle fibers, variation in fiber size, fiber splitting, increased numbers of central nuclei, and endomysial fibrosis. Certain subtypes, particularly in dysferlin deficiency (LGMD2B) may show inflammatory infiltrates, which may lead to an inaccurate diagnosis of polymyositis.

Following standard histologic analysis, immunohistochemistry and immunoblotting are typically used to evaluate myocyte protein components, which may include sarcolemma-related proteins (eg, α-dystroglycan, sarcoglycans, dysferlin, caveolin-3), cytoplasmic proteins (eg, calpain-3, desmin), or nuclear proteins (eg, lamin A/C). Characteristic findings on muscle biopsy immunostaining or immunoblotting can be seen for calpainopathy (LGMD2A), sarcoglycanopathies (LGMD2C-2F), dysferlinopathy (LGMD2B), and O-linked glycosylation defects (dystroglycanopathies; LGMD2I, LGMD2K, LGMD2M, LGMD2O, LGMD2N). However, muscle biopsy is imperfect: secondary deficiencies in protein expression can be seen in some LGMD. In the Moore study (previously described), 9% of all muscle biopsy samples had reduced expression of more than one protein tested. In some variants, muscle immunohistochemistry results may be misleading because the variant leads to normal protein amounts but abnormal function. For example, Western blot analysis for calpain-3, with loss of all calpain-3 bands, may be diagnostic of LGMD2A, but the test is specific but not sensitive, because some LGMD2A patients may retain normal amounts of nonfunctional protein.

A blood-based dysferlin protein assay, which evaluates dysferlin levels in peripheral blood CD14 (cluster of differentiation 14)-positive monocytes, has been evaluated in a sample of 77 individuals with suspected dysferlinopathy. However, the test is not yet in widespread use.

Treatment

At present, no therapies have been clearly shown to slow the progression of muscle weakness for the limb-girdle muscular dystrophies. Treatment is focused on supportive care to improve muscle strength, slow decline in strength, preserve ambulation, and treat and prevent musculoskeletal complications that may result from skeletal muscle weakness, such as contractures or scoliosis. Clinical management guidelines are available from the American Academy of Neurology and Association of Neuromuscular & Electrodiagnostic Medicine.

Monitoring for Complications

Different genetic variants associated with clinical limb-girdle muscular dystrophy are associated with different rates of complications and the speed and extent of disease progression.

Monitoring for respiratory depression and cardiac dysfunction is indicated for limb-girdle muscular dystrophy subtypes associated with respiratory or cardiac involvement, because patients are often asymptomatic until they have significant organ involvement. When respiratory depression is present, patients may be candidates for invasive or noninvasive mechanical ventilation. Treatments for cardiac dysfunction potentially include medical or device-based therapies for heart failure or conduction abnormalities.

Patients may need monitoring and treatment for swallowing dysfunction, if it is present, along with physical and occupation therapy and bracing for management of weakness.

Investigational Therapies

A number of therapies are under investigation for limb-girdle muscular dystrophy. Glucocorticoids have been reported to have some benefit in certain subtypes (LGMD2D, LGMD2I, LGMD2L). However, a small (N=25) randomized, double-blind, placebo-controlled trial of the glucocorticoid deflazacort in patients with genetically confirmed LGMD2B (dysferlinopathy) showed no benefit and a trend toward worsening strength associated with therapy. Autologous bone marrow transplant has been investigated for limb-girdle muscular dystrophy, but is not in general clinical use. Adeno-associated virus-mediated gene transfer to the extensor digitorumbrevis muscle has been investigated in LGMD2D, and in a phase 1 trial in LGMD2C. Exon-skipping therapies have been investigated as a treatment for dysferlin gene variants (LGMD2B) given the gene’s large size.

Molecular Diagnosis

Because most variants leading to limb-girdle muscular dystrophy are single nucleotide variants, the primary method of variant detection is gene sequencing using Sanger sequencing or next-generation sequencing methods. In cases in which a limb-girdle muscular dystrophy is suspected, but gene sequencing is normal, deletion and duplication analysis through targeted comparative genomic hybridization or multiplex ligation-dependent probe amplification may also be obtained.

A number of laboratories offer panels of tests for limb-girdle muscular dystrophy that rely on Sanger sequencing or next-generation sequencing. The following list is not exhaustive.

• GeneDx offers the Limb-Girdle Muscular Dystrophy Panel. This panel uses next-generation sequencing and reports only on panel genes, with concurrent targeted array comparative genomic hybridization analysis to evaluate for deletions and duplications for most genes (exceptions, GMPPB and TNPO3). Multiplex polymerase chain reaction assay is performed to assess for the presence of the 3′ untranslated region insertion in the FKTN gene. All reported sequence variants are confirmed by conventional di-deoxy DNA sequence analysis, quantitative polymerase chain reaction, multiplex ligation-dependent probe amplification, repeat polymerase chain reaction analysis, or another appropriate method.

• Prevention Genetics offers several limb-girdle muscular dystrophy tests. They include an autosomal dominant limb-girdle muscular dystrophy Sanger sequencing panel, which includes MYOT, LMNA, DNAJB6, and CAV3 sequencing either individually or as a panel, followed by array comparative genomic hybridization for deletions and duplications. The company also offers an autosomal recessive limb-gridle muscular dystrophy Sanger sequencing panel, which includes sequencing of SGCG, SGCA, SGCB, SGCD, TRIM32, CAPN3, DYSF, FKRP, TTN, TCAP, GMPPB, ANO5, and TRAPPC11, either individually or as a panel, followed by array comparative genomic hybridization for deletions/duplications. Also, Prevention Genetics offers two next-generation sequencing panels for limb-girdle muscular dystrophy, which involve next-generation sequencing followed by array comparative genomic hybridization if the variant analysis is negative. Additional Sanger sequencing is performed for any regions not captured or with an insufficient number of sequence reads. All pathogenic, undocumented and questionable variant calls are confirmed by Sanger sequencing.

• Counsyl offers a Foresight™ Carrier Screen, which includes testing for multiple diseases that may require early intervention or cause shortened life or intellectual disability and is designed as a carrier test for reproductive planning. Testing for LGMD2D and LGMD2E may be added to the panel. Testing is conducted by next-generation sequencing, without evaluation for large duplications or deletions.

• Centogene (Rostock) offers a next-generation sequencing panel for Muscular Dystrophy, not specific to limb-girdle muscular dystrophy, which includes sequencing of the included variants

   and deletion and duplication testing by multiplex ligation-dependent probe amplification, with whole genome sequencing if no variants are identified.

• Athena Diagnostics offers next-generation sequencing

   testing for FKRP, LMNA, DYSF, CAV3, and CAPN3 (next-generation sequencing followed by dosage analysis), along with a next-generation sequencing panel, with deletion and duplication testing for SGCA, SGCG, and CAPN3.

Variants included in some of the currently available next-generation sequencing testing panels are summarized in the table below.

Table 2: Limb-Girdle Muscular Dystrophy Variants Included in Commercial Next-Generation Sequencing Test Panels

(a) This panel also includes testing for SMCHD1, which is associated with facioscapulohumeral muscular dystrophy(b) This panel also includes testing for PNPLA2, which is associated with neutral lipid storage disease with myopathy and TOR1AIP1.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Tests from laboratories such as GeneDx, Prevention Genetics, Centogene, Counsyl, and Athena Diagnostics are offered under the auspices of CLIA. Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of these tests.

Related medical policies –

• Genetic Testing for Duchenne and Becker Muscular Dystrophy

POLICY

Genetic testing for genes associated with limb-girdle muscular dystrophy (LGMD) to confirm a diagnosis of LGMD may be considered medically necessary when signs and symptoms of LGMD are present but a definitive diagnosis cannot be made without genetic testing, and when at least one of the following criteria are met:

• Results of testing may lead to changes in clinical management that improve outcomes (eg, confirming or excluding the need for cardiac surveillance); OR

• Genetic testing will allow the affected individual to avoid invasive testing, including muscle biopsy;

Genetic testing for genes associated with limb-girdle muscular dystrophy (LGMD) in the reproductive setting may be considered medically necessary when:

• There is a diagnosis of LGMD in one or both of the parents, AND

• Results of testing will allow informed reproductive decision making.

Targeted genetic testing for a known familial variant associated with LGMD may be considered medically necessary in an asymptomatic individual to determine future risk of disease when the following criteria are met:

• The individual has a close (ie, first- or second-degree) relative with a known familial variant consistent with LGMD

                  AND

• Results of testing will lead to changes in clinical management (eg, confirming or excluding the need for cardiac surveillance).

Genetic testing for genes associated with LGMD may be considered medically necessary in an asymptomatic individual to determine future risk of disease when the following criteria are met:

• The individual has a close (ie, first- or second-degree) relative diagnosed with LGMD whose genetic status is unavailable,AND

• Results of testing will lead to changes in clinical management (eg, confirming or excluding the need for cardiac surveillance).

Genetic testing for genes associated with LGMD is considered investigational in all other situations.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Limb-Girdle Muscular Dystrophy

Clinical signs and symptoms of limb-girdle muscular dystrophy (LGMD) include gradually progressive muscle weakness involving predominantly the proximal arms and legs, with normal sensory examination. Distal muscles may be involved, but usually to a lesser extent. Supportive laboratory test results include an elevated creatine kinase (CK) level.

Evaluation and diagnosis of limb-girdle muscular dystrophy should be carried out by providers with expertise in neuromuscular disorders. The 2014 guidelines from the American Academy of Neurology (AAN) and American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) on treatment of limb-girdle muscular dystrophy recommend that “clinicians should refer patients with muscular dystrophy to a clinic that has access to multiple specialties (eg, physical therapy, occupational therapy, respiratory therapy, speech and swallowing therapy, cardiology, pulmonology, orthopedics, and genetics) designed specifically to care for patients with muscular dystrophy and other neuromuscular disorders in order to provide efficient and effective long-term care.”

Testing Strategy

The 2014 American Academy of Neurology and American Association of Neuromuscular & Electrodiagnostic Medicine joint guidelines have outlined an algorithmic approach to narrowing the differential diagnosis in an individual with suspected limb-girdle muscular dystrophy to allow focused genetic testing. The guidelines have indicated: “For patients with a suspected muscular dystrophy, clinicians should use a clinical approach to guide genetic diagnosis based on the clinical phenotype, including the pattern of muscle involvement, inheritance pattern, age at onset, and associated manifestations.” In general, the guidelines have recommended the use of targeted genetic testing if specific features are present based on clinical findings and muscle biopsy characteristics. If there are no characteristic findings on initial targeted genetic testing or muscle biopsy, then next-generation sequencing panels should be considered.

The evaluation of suspected limb-girdle muscular dystrophy should begin, if possible, with targeted genetic testing of one or several single genes based on the individual's presentation. However, if initial targeted genetic testing results are negative or if clinical features do not suggest a specific genetic subtype, testing with a panel of genes known to be associated with limb-girdle muscular dystrophy may be indicated.

Genetics Nomenclature Update

The Human Genome Variation Society nomenclature is used to report information on variants found in DNA and serves as an international standard in DNA diagnostics. It was implemented for genetic testing medical evidence review updates in 2017 (see Table 1). The Human Genome Variation Society's nomenclature is recommended by the Human Variome Project, the Human Genome Organization, and by the Human Genome Variation Society itself.

The American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines for interpretation of sequence variants represent expert opinion from both organizations, in addition to the College of American Pathologists. These recommendations primarily apply to genetic tests used in clinical laboratories, including genotyping, single genes, panels, exomes, and genomes. Table 2 shows the recommended standard terminology—“pathogenic,” “likely pathogenic,” “uncertain significance,” “likely benign,” and “benign”—to describe variants identified that cause Mendelian disorders.

Table 1. Nomenclature to Report on Variants Found in DNA

Table 2. ACMG-AMP Standards and Guidelines for Variant Classification

Genetic Counseling

Experts recommend formal genetic counseling for individuals who are at risk for inherited disorders and who wish to undergo genetic testing. Interpreting the results of genetic tests and understanding risk factors can be difficult for some individuals. Therefore, genetic counseling helps individuals understand the impact of genetic testing, including the possible effects the test results could have on the individual or their family members. It should be noted that genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. 

POLICY HISTORY

07/16/2015: Approved by Medical Policy Advisory Committee.

08/14/2015: Medical policy revised to add ICD-10 codes.

06/07/2016: Policy number A.2.04.132 added.

06/19/2017: Policy title changed from "Mutation Testing for Limb-Girdle Muscular Dystrophies" to "Genetic Testing for Limb-Girdle Muscular Dystrophies." Policy description updated to change "mutations" to "variants" and to add information regarding laboratory testing. Policy statements updated to change "mutations" to "genes." Medically necessary statement revised to separate "targeted genetic testing for a known familial variant" from "genetic testing for genes associated with LGMD" in asymptomatic individuals. Policy Guidelines updated regarding standard terminology for variant classification and to add genetic counseling information.

06/27/2017: Code Reference section updated to revise code description for CPT code 81404, effective 07/01/2017.

12/22/2017: Code Reference section updated to revise descriptions for CPT code 81404 effective 01/01/2018.

05/02/2018: Policy description updated regarding test panels. Policy statements unchanged. Policy Guidelines updated regarding genetic counseling.

09/26/2018: Code Reference section updated to add new ICD-10 diagnosis codes G71.00, G71.02, and G71.09, effective 10/01/2018.

05/08/2019: Policy reviewed; no changes.

05/18/2020: Policy description updated regarding laboratories and test panels. Policy statements unchanged. Code Reference section updated to remove deleted ICD-10 diagnosis code G71.0 and ICD-9 diagnosis code 359.1.

07/23/2021: Policy description updated. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

05/25/2022: Policy reviewed; no changes.

09/30/2022: Code Reference section updated to add new ICD-10 diagnosis codes G71.031, G71.032, G71.033, G71.0340, G71.0341, G71.0342, G71.0349, G71.035, G71.038, and G71.039, effective 10/01/2022.

05/08/2023: Policy reviewed. Policy statement and Policy Guidelines updated to change "patient" to "individual."

05/13/2024: Policy reviewed; no changes.

07/29/2024: Policy updated to change the medical policy number from “A.2.04.132” to “L.2.04.459.”

10/01/2025: Code Reference section updated to add new ICD-10 diagnosis code G71.036.

SOURCE(S)

Blue Cross and Blue Shield Association Policy # 2.04.132

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

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