| Coverage Policy Manual | |
| Policy #: | 2013012 |
| Category: | Laboratory |
| Initiated: | March 2013 |
| Last Review: | April 2024 |
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| Genetic Test: Duchenne and Becker Muscular Dystrophy | |
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| Description: |
Variants in the Duchenne muscular dystrophy (DMD) gene, which encodes the protein dystrophin, may result in a spectrum of X-linked muscle diseases, including the progressive muscle diseases Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) and dilated cardiomyopathy. Genetic testing can confirm a diagnosis of a dystrophinopathy and distinguish the less and more severe forms, as well as identify female carriers at risk.
Background
The dystrophinopathies include a spectrum of muscle diseases. The mild end of the spectrum includes asymptomatic increases in serum concentration of creatine phosphokinase and clinical symptoms such as muscle cramps with myoglobinuria and/or isolated quadriceps myopathy. The severe end of the spectrum includes progressive muscle diseases that lead to substantial morbidity and mortality. When skeletal muscle is primarily affected, the disease is classified as Duchenne or Becker muscular dystrophy and when the heart is primarily affected, as DMD-associated dilated cardiomyopathy (left ventricular dilation and congestive heart failure).
Duchenne Muscular Dystrophy
DMD, the most common muscular dystrophy, is a severe childhood X-linked recessive disorder that results in significant disability due to skeletal myopathy and cardiomyopathy. The disease is characterized by progressive, symmetric muscle weakness and gait disturbance resulting from a defective dystrophin gene (Verma, 2010). According to a 2022 systematic review and meta-analysis, the global prevalence of DMD is estimated at 4.8 cases (95% confidence interval [CI], 3.6 to 6.3) per 100,000people (Salari, 2022). Approximately one-third of DMD cases arise from de novo variants and have no known family history (Verma, 2010). Infant males with DMD are often asymptomatic. Manifestations may be present as early as the first year of life in some patients, but clinical manifestations most often appear during preschool, from years 2 to 5. Affected children present with gait problems, calf hypertrophy, positive Gower sign, and difficulty climbing stairs. The affected child’s motor status may plateau between 3 and 6 years of life with deterioration beginning at 6 to 8 years. Most patients will be wheelchair bound by ages 9 to 12 years but will retain preserved upper-limb function until a later period. Cardiomyopathy occurs after 18 years of age. Late complications are cardiorespiratory (e.g., decreased pulmonary function as a result of respiratory muscle weakness and cardiomyopathy). These severe complications commonly appear in the second decade of life and eventually lead to death (Verma, 2010). Few individuals with DMD survive beyond the third decade.
Becker muscular dystrophy
Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. Individuals remain ambulatory into their 20s. Despite the milder skeletal muscle involvement, heart failure from cardiomyopathy is a common cause of morbidity and the most common cause of death in these patients, with a mean age of death in the mid-40s (Darras, 2014). According to a 2022 systematic review and meta-analysis, the global prevalence of BMD is estimated at 1.6 cases (95% CI, 1.1 to 2.4) per 100,000 people (Salari, 2022).
Female carriers
Females heterozygous for a DMD mutation can manifest symptoms of the disease (Yoon, 2011). An estimated 2.5% to 7.8% of female carriers are manifesting carriers who develop symptoms ranging from a mild muscle weakness to a rapidly progressive DMD-like muscular dystrophy (Soltanzadeh, 2010). Female carriers are at increased risk for dilated cardiomyopathy. Most heterozygous women do not show severe myopathic features of DMD possibly due to compensation by a normal X chromosome with inactivation of the mutated DMD gene in the affected X chromosome (Bonilla, 1998). In some cases, this compensation can be reversed by a non-random or skewed inactivation of X chromosome resulting in greater expression of the affected X chromosome and some degree of myopathic features (Yoshioka, 1998). Other mechanisms of manifesting female carriers include X chromosome rearrangement involving the DMD gene and complete or partial absence of the X chromosome (Turner syndrome) (Yoon, 2011).
Clinical diagnosis
DMD
Suspicion of DMD should be considered irrespective of family history and is most commonly triggered by an observation of abnormal muscle function in a male child, the detection of an increase in serum creatine kinase tested for unrelated indications, or after the discovery of increased serum transaminases (aspartate aminotransferase and alanine aminotransferases). Clinical examination by a neuromuscular specialist for DMD includes visual inspection of mechanical function such as running, jumping, climbing stairs and getting up from the floor. Common presenting symptoms include abnormal gait with frequent falls, difficulties in rising from the floor or in tip-toe walking, and pseudo hypertrophy of the calves. A clinical examination may reveal decreased or lost muscle reflexes and commonly a positive Gower sign. An elevation of serum creatine kinase (CK), at least 10-20 times normal levels (between 5000 and 150,00 IU/L), is non-specific to DMD but is always present in affected patients (Verma, 2010). Electromyography and nerve-conduction were traditional parts of the assessment of neuromuscular disorders but now these tests are no longer believed to be necessary for the specific assessment of DMD (Bushby, 2010). An open skeletal muscle biopsy is needed when a negative test for deletions or duplications to the DMD gene is negative. The biopsy will provide general signs of muscular dystrophy including muscle fiber degeneration, muscle regeneration, and increased content of connective tissue and fat. Dystrophin analysis on a muscle biopsy will always be abnormal in affected patients but is not specific to DMD.
BMD
BMD has a clinical picture similar to DMD but is milder than DMD and has a later onset. BMD presents with progressive symmetric muscle weakness, often with calf hypertrophy, although weakness of quadriceps femoris may be the only sign. Activity-induced cramping may be present in some individuals, and flexion contractures of the elbows may be present late in the course. Neck flexor muscle strength is preserved, which differentiates BMD from DMD. Serum creatine kinase shows moderate-to-severe elevation (5-100 times the normal level).
Molecular diagnosis
DMD is the only gene in which mutations are known to cause DMD, BMD and DMD-associated cardiomyopathy. Molecular genetic testing of DMD can establish the diagnosis of a dystrophinopathy without muscle biopsy in most patients with DMD and BMD.
The dystrophinopathies are x-linked recessive and penetrance is complete in males. The gene that codes for dystrophin is the largest known human gene (Verma, 2010). A molecular confirmation of DMD and BMD is achieved by confirming the presence of a pathogenic variant in this gene by a number of available assays. The large size of the dystrophin gene results in a complex mutational spectrum with over 5000 reported disease-associated variants, as well as a high spontaneous de novo variant rate (Mah, 2011).
Treatment of Duchenne Muscular Dystrophy
There is no cure for Duchenne or Becker muscular dystrophy and treatment is aimed at control of symptoms to improve quality of life. However, the natural history of the disease can be changed by several strategies such as corticosteroid therapy, proper nutrition or rehabilitative interventions. Glucocorticoids were shown in a 1991 randomized controlled trial to prolong the period of independent ambulation by 3 years (Griggs, 1991). The goal of this therapy is to preserve ambulation and minimize later respiratory, cardiac, and orthopedic complications. Glucocorticoids work by decreasing inflammation, preventing fibrosis, improving muscle regeneration, improving mitochondrial function, decreasing oxidative radicals, and stopping abnormal apoptosis pathways (Verma, 2010). Bone density measurement and immunization are prerequisites for corticosteroid therapy initiation which typically begins at 2 to 5 years of age although there has been no demonstrated benefit of earlier therapy before 5 years of age (Verma, 2010).
New therapeutic trials require accurate diagnoses of these disorders, especially when the therapy is targeted at specific pathogenic variants (Abbs, 2010). Exon-skipping is a molecular therapy aimed at skipping the transcription of a targeted exon to restore a correct reading frame using antisense oligonucleotides. Exon-skipping may result in a DMD protein without the mutated exon and a normal, nonshifted reading frame. Exon-skipping may also restore DMD protein function so that the treated patient’s phenotypic expression more closely resembles BMD. Several therapies are currently in clinical trials. Exon-skipping therapies using antisense oligonucleotides approved by the U.S. Food and Drug Administration include: eteplirsen (Exondys 51) for treatment for patients who have a confirmed variant of the dystrophin gene amenable to exon 51 skipping, and golodirsen (Vyondys 53), and viltolarsen (Viltepso) for patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. These approvals were based on improvements in the surrogate outcome of increased dystrophin production in skeletal muscle and benefits in clinical outcomes have not yet been established (FDA, 2016; FDA, 2019; FDA, 2020).
Regulatory Status
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; such tests must meet the general regulatory standards of the Clinical Laboratory Improvement Act (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 this test.
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Policy/ Coverage: |
EFFECTIVE APRIL 2017
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Genetic testing for DMD gene variants meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes under the following conditions:
Note: At-risk females are defined as first- and second-degree female relatives and include the proband’s mother, female siblings of the proband, female offspring of the proband, the proband’s maternal grandmother, maternal aunts, and their offspring. An at-risk male is defined as an asymptomatic male offspring of a female carrier or an asymptomatic male sibling of a patient with a DMD-associated dystrophinopathy.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Genetic testing for DMD gene variants in any other circumstance does not meet member benefit primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, genetic testing for DMD gene variants in any other circumstances is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage
EFFECTIVE PRIOR TO APRIL 2017
Genetic testing for DMD gene mutations meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes under the following conditions:
Genetic testing for DMD gene mutations in any other circumstance does not meet member benefit primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, genetic testing for DMD gene mutations in any other circumstances is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
Analytic validity (refers to the technical accuracy of the test in detecting a mutation that is present or in excluding a mutation that is absent)
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
DMD is the only gene of which variants are known to cause DMD, BMD, and DMD-associated cardiomyopathy. Molecular genetic testing of DMD can establish the diagnosis of a dystrophinopathy without muscle biopsy in approximately 95% of patients with DMD and BMD (Andrews, 2023).
Deletions of one or more exons account for 60-70% of mutations in individuals with DMD and BMD (Takeshima, 2010). Duplications account for 5-10% of mutations in DMD and BMD(Takeshima, 2010).
Multiplex PCR may be used to amplify exons known to be most frequently deleted in DMD affected patients. Results obtained from testing two PCR multiplex sets suggest a detection rate of approximately 98% with this methodology (Beggs, 1990; Chamberlain, 1988). Multiplex PCR is the most widely available testing choice, but is only able to detect deletions. In addition, this method does not cover the whole gene so a deletion might not always be fully characterized (Bushby, 2010). An alternative to multiplex PCR is the use of a quantitative assay (e.g. multiplex ligation-dependent probe amplification or comparative genomic hybridization [also called chromosomal microarray or CMA]) of all exons. These methods have the advantage of being able to detect whole exon deletions as well as duplications.
Point mutations (small deletions or insertions, single-base changes, and splicing mutations) account for approximately 25-35% of mutations in males with DMD and about 10-20% of males with BMD. If deletion/duplication detection is negative, then dystrophin gene sequencing should be done to look for point mutations or small deletions/insertions (Bushby, 2010). Sequencing of the entire DMD gene to detect point mutations can be performed by traditional PCR and Sanger sequencing, or by more automated methods such as universal long PCR combined with massive pyrosequencing.
There is a lack of published studies in the peer-review literature that evaluate analytic validity. According to information from the website of a large reference laboratory, deletion/duplication analysis by CMA and point mutations by full gene sequencing detects 98-99% of mutations in both males and females (Emory Genetics Laboratory).
Certain types of assays may cause false positive results if the method identifies an apparent single exon deletion or duplication based on the absence or increased amplification, respectively, of a single PCR amplification, or hybridization- when this occurs, the result must be confirmed using an alternative assay. This different assay will verify whether the initial result could have been caused by a sequence variant preventing hybridization of a primer, probe, etc., or for duplications, if the result was an anomaly. Therefore, false positives are expected to be infrequent.
Clinical validity (refers to the diagnostic performance of the test- sensitivity, specificity, positive and negative predictive values)
Virtually all males with DMD/BMD have identifiable DMD mutations, indicating a high clinical sensitivity for genetic testing. In males with DMD and BMD, phenotypes are best correlated with the degree of expression of dystrophin, largely determined by the reading frame of the spliced message obtained from the deleted allele.
A reading frame is the way in which a messenger RNA sequence of nucleotides can be read as a series of base triplets, and affects which protein is made. In DMD, the function of the dystrophin protein is completely lost due to mutations that disrupt the reading frame. Therefore, prematurely truncated, unstable dystrophins are generated. In contrast, patients with BMD have low levels of full-length dystrophin or carry in-frame mutations that allow for the generation of partially functional proteins. This so-called reading frame rule explains the phenotypic differences between DMD and BMD patients. Since this rule was postulated in 1988 (Monaco, 1988), thousands of mutations have been reported for DMD and BMD, of which an estimated 90% fit this rule (Aartsma-Rus, 2006).
Testing strategy
To establish the diagnosis of a proband with DMD or BMD in a male with clinical findings that suggest a dystrophinopathy:
For carrier testing in at-risk female relatives:
The evaluation of relatives at risk includes females who are the sisters or maternal female relatives of an affected male and females who are a first-degree relative of a known or possible carrier female.
Clinical utility (how the results of the diagnostic test will be used to change management of the patient and whether these changes in management lead to clinically important improvements in health outcomes)
The clinical utility of testing for DMD gene mutations for the index case includes:
The clinical utility of testing for DMD gene mutations for at-risk female relatives includes
Summary
The analytic and clinical validity of genetic testing for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are high. DMD is the only gene in which mutations cause the dystrophinopathies, and molecular genetic testing can establish the diagnosis in most patients. Nearly all affected individuals will be found to have a DMD mutation, and false positives are expected to be rare. The clinical utility of DMD gene testing can be established for the index case and for at-risk female relatives. For the index case, utility lies in confirmation of the diagnosis without a muscle biopsy, initiation of effective treatment, and in distinguishing between DMD and the less severe BMD. For at-risk female relatives, the test can confirm or exclude the need to undergo routine cardiac surveillance, and can indicate the likelihood of an affected offspring in women considering children.
Practice Guidelines and Position Statements
A meeting of 29 senior scientists from Europe, the USA, India and Australia established consensus Best Practice Guidelines for the molecular diagnosis of DMD/BMD. The recommendations for testing are, if there is a clinical suspicion of a dystrophinopathy, first screen for deletions and duplications. If no deletion or duplication is detected, but the clinical diagnosis is verified, screening for point mutations should be performed (Abbs, 2010).
2014 Update
A literature search conducted through February 2014 did not identify any new information that would prompt a change in the coverage statement.
2015 Update
A literature search conducted through February 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Wang and colleagues used next generation sequencing (NGS) of the entire DMD gene to detect point mutations in 10 males with DMD, 5 of whom were negative and 5 of whom were positive for deletions and duplications (Wang, 2014). In the 5 deletion/duplication-negative patients, all identified mutations considered pathogenic were validated by Sanger sequencing, including 4 novel variants. In the 5 deletion/duplication-positive patients, NGS detected deletions and duplications by breakpoint analysis. Because NGS breakpoint analysis requires development of precise primers to identify and verify breakpoints, clinical use of NGS for this purpose is limited.
2016 Update
A literature search conducted through January 2016 did not reveal any new information that would prompt a change in the coverage statement.
March 2017 Update
This update focuses on testing male offspring of a female carrier or male sibling of a patient with a DMD-associated dystrophinopathy.The purpose of genetic testing of male offspring of a female DMD familial variant carrier or male sibling of a patient with a DMD-associated dystrophinopathy is to diagnose at-risk males prior to manifestation of disease and initiate medical and cardiac surveillance. At-risk males with an identified DMD familial variant will undergo surveillance for cardiac and myopathic manifestations. Males who do not have the DMD familial variant can avoid surveillance that would be indicated by knowledge of family history alone.
Clinical Validity
In male offspring of a female DMD familial variant carrier or male sibling of a patient with a DMD-associated dystrophinopathy, the presence of a DMD familial variant is predictive of future developing clinical manifestations of a DMD-associated dystrophinopathy (Ross, 2013).
Testing Strategy
For DMD familial variant testing in at-risk male offspring or sibling:
The evaluation of relatives at risk includes male offspring of a female DMD familial variant carrier or a male sibling of a patient with DMD-associated dystrophinopathy.
Summary: Clinical Validity
Evidence from studies have indicated that the clinical sensitivity of genetic testing is high given that DMD is the only gene for which variants are known to cause DMD, BMD, and DMD-associated cardiomyopathy. For male offspring of female carriers or male siblings of an affected male with a DMD-associated dystrophinopathy, targeted DMD familial variant testing confirms or excludes diagnosis of a DMD-associated dystrophinopathy prior to manifestation of disease.
Clinical Utility
Clinical utility is how the results of the diagnostic test will be used to change management of the patient and whether these changes in management lead to clinically important improvements in health outcomes.
No published studies showing the clinical utility of testing for DMD gene variants were identified. As outlined next, clinical utility is established based on the benefits of testing for asymptomatic male offspring of a female DMD familial variant carrier or an asymptomatic male sibling of a patient with a DMD-associated dystrophinopathy is to confirm or exclude diagnosis of a DMD-associated dystrophinopathy prior to manifestation of disease.
The clinical utility of testing at-risk male offspring or male siblings for DMD gene variants includes:
Section Summary: Clinical Utility
Direct evidence of the clinical utility of genetic testing in individuals who are asymptomatic male offspring of a female DMD familial variant carrier or asymptomatic male siblings of a patient with DMD-associated dystrophinopathy is lacking. A chain of evidence exists in that confirmation or exclusion of a DMD familial variant predicts clinical manifestations in asymptomatic at-risk males and necessitates or eliminates the need for medical and cardiac surveillance.
SUMMARY OF EVIDENCE
The purpose of genetic testing of male offspring of a female DMD familial variant carrier or male sibling of a patient with a DMD-associated dystrophinopathy is to diagnose at-risk males prior to manifestation of disease and initiate medical and cardiac surveillance. At-risk males with an identified DMD familial variant
For individuals who are asymptomatic male offspring of a female DMD familial variant carrier or an asymptomatic male sibling of a patient with a DMD-associated dystrophinopathy, the evidence includes case series and database entries. Relevant outcomes are test accuracy and validity, symptoms, change in disease status, morbid events, quality of life, medication use, and resource utilization. Published data for the analytic and clinical validity of testing for a known familial variant are lacking, but the validity is expected to be high. Direct evidence on the clinical utility of DMD gene testing in asymptomatic male offspring of a female DMD familial variant carrier or male sibling of a patient with a DMD-associated dystrophinopathy is lacking. However, the chain of evidence is strong, because detection of the DMD familial variant necessitates or eliminates the need for increased medical surveillance or cardiac surveillance in an asymptomatic male of a female carrier or the asymptomatic male sibling of a patient with a DMD-associated dystrophinopathy. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. The policy statement has been changed to reflect this determination.
2018 Update
A literature search conducted using the MEDLINE database did not reveal any new information that would prompt a change in the coverage statement.
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2019. No new literature was identified that would prompt a change in the coverage statement.
2020 Update
A literature search was conducted through January 2020. There was no new information identified that would prompt a change in the coverage statement.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2021. No new literature was identified that would prompt a change in the coverage statement.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
In 2018, the DMD Care Considerations Working Group updated its Care Considerations recommendations (Birnkrant, 2018). Their recommendations for genetic testing utilization in DMD diagnosis remained similar to their 2010 recommendations, with a recommendation to first screen for deletions and duplications, followed by genetic sequencing if no deletion or duplication is detected. A muscle biopsy is only recommended if genetic testing does not confirm a clinical diagnosis and DMD is still considered likely. The working group also recommended genetic counseling to family members of an individual with DMD to establish who is at risk of being a carrier. Carrier testing is recommended for female relatives of a male who has been genetically confirmed to have DMD.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2023. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
In 2020, the best practice guidelines were updated to summarize current recommended technologies and methodologies in DMD gene analysis (Fratter, 2020). The guideline's recommendations for testing are similar to 2010 recommendations. In terms of an initial screen, a diagnostic test that detects whole-exon deletions or duplications should be offered to detect copy number variations. Use of RNA-based analysis is recommended in patients with a clinical diagnosis of dystrophinopathy but no copy number variations or small variants that were identified.
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
DMD is the only gene of which variants are known to cause DMD, BMD, and DMD-associated cardiomyopathy. Molecular genetic testing of DMD can establish the diagnosis of a dystrophinopathy without muscle biopsy in approximately 95% of patients with DMD and BMD (Andrews, 2023).
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
DMD is the only gene of which variants are known to cause DMD, BMD, and DMD-associated cardiomyopathy. Molecular genetic testing of DMD can establish the diagnosis of a dystrophinopathy without muscle biopsy in approximately 95% of most patients with DMD and BMD (Andrews, 2023).
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| References: |
Aartsma-Rus A, Van Deutekom JC, Fokkema IF et al.(2006) Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve 2006; 34(2):135-44. Abbs S, Tuffery-Giraud S, Bakker E et al.(2010) Best practice guidelines on molecular diagnostics in Duchenne/Becker muscular dystrophies. Neuromuscul Disord 2010; 20(6):422-7. Andrews JG, Galindo MK, Thomas S, et al.(2023) DMD Gene and Dystrophinopathy Phenotypes Associated With Mutations: A Systematic Review for Clinicians. J Clin Neuromuscul Dis. Jun 01 2023; 24(4): 171-187. PMID 37219861 Beggs AH, Koenig M, Boyce FM et al.(1990) Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 1990; 86(1):45-8. Birnkrant DJ, Bushby K, Bann CM, et al.(2018) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, andneuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. Mar 2018; 17(3):251-267. PMID 29395989 Bonilla E, Schmidt B, Samitt CE et al.(1998) Normal and dystrophin-deficient muscle fibers in carriers of the gene for Duchenne muscular dystrophy. Am J Pathol 1988; 133(3):440-5. Bowles DE, McPhee SW, Li C et al.(2012) Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther 2012; 20(2):443-55. Bushby K, Finkel R, Birnkrant DJ et al.(2010) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010; 9(1):77-93. Chamberlain JS, Gibbs RA, Ranier JE et al.(1988) Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 1988; 16(23):11141-56. Chen WJ, Lin QF, Zhang QJ et al.(2013) Molecular analysis of the dystrophin gene in 407 Chinese patients with Duchenne/Becker muscular dystrophy by the combination of multiplex ligation-dependent probe amplification and Sanger sequencing. Clin Chim Acta 2013; 423:35-8. Darras BT, Miller DT, Urion DK.(2014) Dystrophinopathies. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews.Seattle, WA: University of Washington; 2014. Emory Genetics Laboratory. Duchenne/Becker Muscular Dystrophy: DMD Gene Deletion/Duplication. http://geneticslab.emory.edu/tests/EG. Accessed February 23, 2015. Emory Genetics Laboratory. Duchenne/Becker Muscular Dystrophy: DMD Gene Sequencing. http://geneticslab.emory.edu/tests/EE. Accessed February 23, 2015. Food and Drug Administration (FDA).(2016) FDA News Release: FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. 2016; https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm. Accessed February 2, 2018. Food and Drug Administration (FDA).(2016) FDA News Release: FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. 2016; https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm. Accessed February 2, 2018. Food and Drug Administration.(2019) VYONDYS 53 (golodirsen) Prescribing Information. 2019 https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211970s000lbl.pdf Accessed January 15, 2021. Food and Drug Administration.(2020) VILTEPSO (viltolarsen) Prescribing Information. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212154Orig1s000lbl.pdf. Accessed January 14, 2021 Fratter C, Dalgleish R, Allen SK, et al.(2020) EMQN best practice guidelines for genetic testing in dystrophinopathies. Eur J HumGenet. Sep 2020; 28(9): 1141-1159. PMID 32424326 Griggs RC, Moxley RT, 3rd, Mendell JR, et al.(1991) Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. Arch Neurol. Apr 1991;48(4):383-388. PMID 2012511 Griggs RC, Moxley RT, 3rd, Mendell JR, et al.(1991) Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. Arch Neurol. Apr 1991;48(4):383-388. PMID 2012511 http://genetics.emory.edu/egl/tests/?testid=120 Kalman L, Leonard J, Gerry N et al.(2011) Quality assurance for Duchenne and Becker muscular dystrophy genetic testing: development of a genomic DNA reference material panel. J Mol Diagn 2011; 13(2):167-74. Koo T, Wood MJ.(2013) Clinical trials using antisense oligonucleotides in duchenne muscular dystrophy. Hum Gene Ther 2013; 24(5):479-88. Laing NG.(2012) Genetics of neuromuscular disorders. Crit Rev Clin Lab Sci 2012; 49(2):33-48. Mah JK, Korngut L, Dykeman J, et al.(2014) A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. Jun 2014;24(6):482-491. PMID 24780148 Mah JK, Korngut L, Dykeman J, et al.(2014) A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. Jun 2014;24(6):482-491. PMID 24780148 Mah JK, Selby K, Campbell C et al.(2011) A population-based study of dystrophin mutations in Canada. Can J Neurol Sci 2011; 38(3):465-74. Monaco AP, Bertelson CJ, Liechti-Gallati S et al.(1988) An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 1988; 2(1):90-5. Ross LF, Saal HM, David KL, et al.(2013) Technical report: Ethical and policy issues in genetic testing and screening of children. Genet Med. Mar 2013;15(3):234-245. PMID 23429433 Salari N, Fatahi B, Valipour E, et al.(2022) Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis. J Orthop Surg Res. Feb 15 2022; 17(1): 96. PMID 35168641 Sansovic I, Barisic I, Dumic K.(2013) Improved detection of deletions and duplications in the DMD gene using the multiplex ligation-dependent probe amplification (MLPA) method. Biochem Genet 2013; 51(3-4):189-201. Soltanzadeh P, Friez MJ, Dunn D et al.(2010) Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscul Disord 2010; 20(8):499-504. Takeshima Y, Yagi M, Okizuka Y et al.(2010) Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J Hum Genet 2010; 55(6):379-88. Verma S, Anziska Y, Cracco J.(2010) Review of Duchenne muscular dystrophy (DMD) for the pediatricians in the community. Clin Pediatr (Phila) 2010; 49(11):1011-7. Wang Y, Yang Y, Liu J, et al.(2014) Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy. Mol Genet Genomics. Oct 2014;289(5):1013-1021. PMID 24770780 Yang J, Li SY, Li YQ et al.(2013) MLPA-based genotype-phenotype analysis in 1053 Chinese patients with DMD/BMD. BMC Med Genet 2013; 14:29. Yoon J, Kim SH, Ki CS et al.(2011) Carrier woman of Duchenne muscular dystrophy mimicking inflammatory myositis. J Korean Med Sci 2011; 26(4):587-91. Yoshioka M, Yorifuji T, Mituyoshi I.(1998) Skewed X inactivation in manifesting carriers of Duchenne muscular dystrophy. Clin Genet 1998; 53(2):102-7. |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association. |
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