ModifiedCentenePolicy N/A

Concert Genetic Testing: Epilepsy, Neurodegenerative, and Neuromuscular Disorders

Genetic testing to establish or confirm diagnoses for patients with signs/symptoms of hereditary epilepsy, neurodegenerative, and neuromuscular disorders when standard evaluation is non-diagnostic; intended for providers ordering genetic testing under Centene plans.

Policy Summary

PayerCentene

PolicyConcert Genetic Testing: Epilepsy, Neurodegenerative, and Neuromuscular Disorders

Policy CodePolicy N/A

Change TypeCriteria revisions & additions

Effective DateN/A

Next Review DateN/A

Key ActionVerify clinical documentation and prior authorization requirements (including age, symptomatic, and prior testing criteria) when ordering genetic testing.

SourceLink

POLICY UPDATE CHANGES

Updated multiple panel titles and expanded or clarified clinical criteria (examples: changed Neuromuscular NGS Panel to Comprehensive Neuromuscular Disorders Panel; added panels such as Rett syndrome and CADASIL).

Added specific clinical features to the Congenital Myasthenic Syndromes panel (neonatal respiratory insufficiency, joint contractures, stridor, abnormal fatigability, delayed milestones, ptosis, facial/bulbar findings, spinal deformity, abnormal EMG).

Added 'or Periodic Paralysis Multigene Panel' to CACNA1S and SCN4A sequencing titles and criteria.

Added age restriction for HTT Repeat Analysis (18 or older), removed age restriction for ALS multigene panel, and specified FXN repeat analysis requires the member to be symptomatic.

Semi-annual review; coding, reference-table, background and references updated; multiple GeneReviews copyright updates (Date of Last Revision: 11/24; version identifiers updated).

11/24Date of Last Revision

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria — Genetic & Molecular Testing

NOTCH3 Sequencing and/or Deletion/Duplication Analysis (CADASIL)

I. NOTCH3 sequencing and/or deletion/duplication analysis (81406, 81479) to establish or confirm a diagnosis of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is considered medically necessary when:

A. The member/enrollee has a family history of stroke and/or vascular dementia consistent with an autosomal dominant pattern of inheritance, OR

1. Transient ischemic attacks and ischemic stroke, OR
2. Cognitive impairment, manifesting initially with executive dysfunction, with a concurrent stepwise deterioration due to recurrent strokes to vascular dementia, OR
3. Migraine with aura (mean age of onset of 30 years), OR
4. Psychiatric disturbances, most frequently mood disturbances and apathy, OR
5. Characteristic brain MRI findings such as symmetric and progressive white matter hyperintensities often involving the anterior temporal lobes and external capsules, lacunes, dilated perivascular spaces, or cerebral microbleeds.

C. Non-genetic causes of the clinical presentation have been reasonably excluded when appropriate (e.g., small vessel disease related to hypertension, vasculitis, demyelinating disease, or other acquired causes), OR

D. Predictive testing in asymptomatic adults is considered only in the context of pre- and post-test genetic counseling and when there is a known familial NOTCH3 pathogenic variant.

CLCN1 Sequencing and/or Deletion/Duplication Analysis

I. CLCN1 sequencing and/or deletion/duplication analysis (81406, 81479) to establish a genetic diagnosis of myotonia congenita is considered medically necessary when:

1. Episodes of muscle stiffness (myotonia) or cramps beginning in early childhood that are alleviated by brief exercise, OR
2. Myotonic contraction elicited by percussion of muscles, OR
3. Electromyography (EMG) discloses characteristic myotonic discharges (myotonic bursts).

II. CLCN1 sequencing and/or deletion/duplication analysis (81406, 81479) to establish a genetic diagnosis of myotonia congenita is considered investigational for all other indications.

CACNA1S and SCN4A Sequencing and/or Deletion/Duplication Analysis, or Periodic Paralysis Multigene Panel

I. CACNA1S and SCN4A sequencing and/or deletion/duplication analysis, or Periodic Paralysis multigene panel (81406, 81479) to establish a genetic diagnosis of periodic paralysis is considered medically necessary when:

A. Alternative causes of hypokalemia have been excluded (e.g., renal, adrenal, thyroid dysfunction; renal tubular acidosis; diuretic and laxative abuse), AND

B. The member/enrollee has had two or more attacks of muscle weakness with documented serum potassium less than 3.5 mEq/L, OR

C. The member/enrollee has had one attack of muscle weakness, AND has a close relative who has had one attack of muscle weakness with documented serum potassium less than 3.5 mEq/L, OR

1. Onset of symptoms in the first or second decade, OR
2. Muscle weakness involving at least 1 limb lasting longer than two hours, OR

Covered Indications — When Testing Is Medically Necessary

Coding — Example CPT/ICD mappings

Comprehensive Neuromuscular Disorders Panel (example CPTs)CPT

81161	Common CPT code listed for Comprehensive Neuromuscular Disorders Panel
81404	Common CPT code listed for Comprehensive Neuromuscular Disorders Panel
81405	Common CPT code listed for Comprehensive Neuromuscular Disorders Panel
81406	Common CPT code listed for Comprehensive Neuromuscular Disorders Panel
81479	Common CPT code listed for Comprehensive Neuromuscular Disorders Panel

(source note)neutral

No codes listed

Comprehensive Ataxia Panel (example CPTs)CPT

0216U	Genomic Unity Ataxia Repeat Expansion Analysis (Variantyx, Inc.)
0217U	Genomic Unity Comprehensive Ataxia Analysis (Variantyx, Inc.)
81185	CPT for Ataxia Panel (example)
81189	CPT for Ataxia Panel (example)
81286	CPT for Ataxia Panel (example)
81403	CPT for Ataxia Panel (example)
81404	CPT for Ataxia Panel (example)
81479	CPT listed with Ataxia panels

(source note)neutral

No codes listed

Spinal Muscular Atrophy / SMN1/SMN2 (example CPTs)CPT

81329	SMN1 sequencing and/or deletion/duplication analysis (Quest Diagnostics example)
81336	SMN1 sequencing (Fulgent Genetics example)
81405	SMN1 related CPT (example)
0236U	Genomic Unity SMN1/2 Analysis (Variantyx Inc.)
81401	SMN2 deletion/duplication analysis (example)

(source note)neutral

No codes listed

Epilepsy multigene panels (example CPTs)CPT

81185	Epilepsy multigene panel example CPT
81189	Epilepsy multigene panel example CPT
81302	CPT included with epilepsy panels / MECP2 sequencing
81406	Epilepsy multigene panel example CPT
81419	Epilepsy multigene panel example CPT
81479	Epilepsy multigene panel example CPT

(source note)neutral

No codes listed

Neurodegenerative disease gene sequencing (example CPTs)CPT

81406	NOTCH3 sequencing and/or del/dup analysis (example)
81479	NOTCH3 and Alzheimer panels listed
81405	PSEN1/PSEN2/APP sequencing del/dup analysis (example)

(source note)neutral

No codes listed

Various neuromuscular and neurodegenerative testing CPTs (examples)CPT

81179	Listed for ALS multigene panel
81403	Listed for ALS and other panels
81407	Listed for ALS multigene panel
81408	Diagnostic DMD sequencing/deldup (GeneDx example)
0218U	Genomic Unity DMD Gene Analysis (Variantyx) example
81404	D4Z4 haplotype / FSHD testing example CPT
81284	FXN repeat analysis (Athena Diagnostics example)
81285	FXN repeat analysis (Athena Diagnostics example)
81286	FXN sequencing example
0233U	HTT repeat analysis / Huntington's Disease example

1–10 of 15

1/2

(source note)neutral

No codes listed

APOE / single gene examplesCPT

81401	APOE variant analysis CPT listed
81479	APOE listed with 81479

(source note)neutral

No codes listed

Example ICD-10 codes referencedICD-10

G12	Example ICD grouping for neuromuscular disorders
G11.1	Ataxia ICD example
G40.001-G40.919	Epilepsy ICD code range example
G60.0	PMP22 / Charcot-Marie-Tooth ICD example
Z84.81	Family history ICD example used across multiple panels

(source note)neutral

No codes listed

PMP22 / related panel codesCPT

81324	PMP22 Sequencing and/or Deletion/Duplication Analysis or Multigene Panel
0233U	PMP22 Sequencing and/or Deletion/Duplication Analysis or Multigene Panel (alternate HCPCS code listed)
81325	PMP22 related code mapping mentioned
81448	NGS Panel / PMP22 related mapping

(source note)neutral

No codes listed

Other covered epilepsy, neuromuscular, and neurodegenerative codesCPT

81400
81401	SMN2 deletion/duplication analysis
81402
81403
81404
81405
81406
81407
81408
81479

(source note)neutral

No codes listed

Key panel and gene-specific codes referenced in criteriamixed

81161	Comprehensive neuromuscular panel code
81185	Ataxia / epilepsy panel related code
81189	Panel code
81286	Ataxia panel related code
81302	MECP2 / epilepsy related code
81329	SMN1 code
81336	SMN1 related code
81419	Epilepsy panel related code
0236U	SMN1 sequencing/deletion-duplication (HCPCS/other)
0234U	MECP2 sequencing/deletion-duplication (HCPCS/other)

1–10 of 12

1/2

(source note)neutral

No codes listed

Myotonic dystrophy / repeat expansion codesCPT

81234	DMPK repeat expansion testing
81239
81401	Repeat analysis / related code
81187
S3853	Supplemental code mentioned for repeat expansion testing

(source note)neutral

No codes listed

Disease-specific sequencing/panel codesCPT

81405	PSEN1 / panel code
81406	PSEN2/APP/other panel code
81448	NGS panel code

(source note)neutral

No codes listed

NOTCH3 Sequencing/Deletion-DuplicationCPTCovered

81406	NOTCH3 sequencing
81479	Unlisted molecular pathology procedure (used here for deletion/duplication analysis)

(source note)neutral

No codes listed

PSEN1/PSEN2/APP Sequencing/Deletion-DuplicationCPTCovered

81405	PSEN1 sequencing
81406	PSEN2/APP sequencing (as listed)
81479	Deletion/Duplication analysis (listed)

(source note)neutral

No codes listed

APOE Variant AnalysismixedCovered

81401	APOE variant analysis
81479	Supporting molecular procedure code
S3852	APOE testing HCPCS/S-code as listed

(source note)neutral

No codes listed

ALS Multigene PanelmixedCovered

81179	Unlisted multigene panel (ALS)
81403	Targeted sequence analysis
81404	Large gene panel sequencing
81405	Multigene panel variant
81406	Multigene panel variant
81407	Multigene panel variant
81479	Misc molecular pathology
S3800	ALS panel S-code

(source note)neutral

No codes listed

DMD Sequencing/Deletion-DuplicationCPTCovered

0218U	DMD sequencing specific code
81161	DMD specific sequencing/deletion-duplication
81408	DMD panel/large panel

(source note)neutral

No codes listed

FSHD D4Z4 Haplotype and SMCHD1/DNMT3B TestingCPTCovered

81404	D4Z4 haplotype / large panel
81479	SMCHD1/DNMT3B sequencing or deletion/duplication

(source note)neutral

No codes listed

FXN Repeat/Sequencing AnalysisCPTCovered

0233U	FXN repeat analysis
81284	FXN repeat testing
81285	FXN repeat testing
81286	FXN sequencing
81404	Sequencing/panel for FXN

(source note)neutral

No codes listed

HTT Repeat Analysis (Huntington disease)CPTCovered

81271	HTT repeat analysis
81274	HTT repeat analysis variant

(source note)neutral

No codes listed

PMP22 Sequencing/Deletion-Duplication and PanelsCPTCovered

81324	PMP22 sequencing
81325	PMP22 deletion/duplication
81448	Multigene panel for inherited peripheral neuropathy

(source note)neutral

No codes listed

Limb-girdle Muscular Dystrophy PanelsCPTCovered

81405	Limb-girdle panel variant
81406	Limb-girdle panel variant
81408	Limb-girdle panel
81479	Misc molecular pathology

(source note)neutral

No codes listed

DMPK and CNBP (ZNF9) Repeat AnalysismixedCovered

81234	DMPK repeat analysis
81239	DMPK testing variant
81401	CNBP/DMPK related code listed
81404	Large panel or sequencing
S3853	Myotonic dystrophy S-code
81187	CNBP repeat analysis

(source note)neutral

No codes listed

Hereditary Dystonia Multigene PanelCPTCovered

81404	Hereditary dystonia panel
81405	Panel variant
81406	Panel variant
81407	Panel variant
81408	Panel variant
81479	Misc molecular pathology

(source note)neutral

No codes listed

Parkinson Disease Multigene PanelCPTCovered

81479

Parkinson disease multigene panel

(source note)neutral

No codes listed

Hereditary Spastic Paraplegia PanelCPTCovered

81448

Hereditary spastic paraplegia multigene panel

(source note)neutral

No codes listed

Congenital Myasthenic Syndromes PanelCPTCovered

81406	Congenital myasthenic syndromes panel sequencing
81407	Congenital myasthenic syndromes panel variant
81479	Misc molecular pathology

(source note)neutral

No codes listed

CLCN1 Sequencing/Deletion-DuplicationCPTCovered

81406	CLCN1 sequencing
81479	CLCN1 deletion/duplication

(source note)neutral

No codes listed

CACNA1S/SCN4A Sequencing and Periodic Paralysis PanelsCPTCovered

81406	CACNA1S/SCN4A sequencing
81479	Periodic paralysis panel/misc molecular pathology

(source note)neutral

No codes listed

Referenced CPT Codes for sequencing and deletion/duplication analysisCPT

81406	Targeted genomic sequence analysis (as listed in document)
81479	Unlisted molecular pathology procedure (used in document for deletion/duplication analysis)

(source note)neutral

No codes listed

No explicit CPT/HCPCS/ICD codes listed in this excerptmixed

No codes listed

Repeat expansion repeat counts (key values)

DMPK (DM1) repeat threshold

Provider Actions & Authorization Requirements

Prior Authorization

Comprehensive Ataxia Panel — Prior Authorization Required

Comprehensive ataxia panels require prior authorization and are medically necessary only when the member has at least one of the listed ataxia clinical features and non‑genetic causes have been excluded. Comprehensive ataxia panels are investigational for other indications.

Tests referenced (e.g., 0216U, 0217U, 81185, 81189, 81286, 81403, 81404, 81479) are informational — verify coding prior to claim submission (chunk 31, chunk 3)

Prior Authorization

SMN1/SMN2 Testing — Prior Authorization Required

SMN1 (and SMN2 when applicable) sequencing and deletion/duplication analyses require prior authorization and are medically necessary only for the listed clinical scenarios (positive newborn screen or symptomatic findings consistent with SMA, or for SMN2 when the member has a diagnosis of SMA). These tests are investigational for other indications.

Verify CPT/HCPCS codes (e.g., 0236U, 81329, 81336, 81405, 81401) before claim submission (chunk 3)

Not Covered / Investigational

Panels and single‑gene tests described in this policy are considered investigational (not covered) for indications other than those specifically enumerated in each test’s criteria. Examples in the policy (e.g., comprehensive ataxia panel, epilepsy multigene panel) include explicit language that the panel is investigational for all other indications.

All indications not explicitly listed under the medically necessary criteria for a specific test or panel are treated as investigational. Providers should document how the member meets the listed clinical, age, and family‑history criteria for the requested test; absence of those criteria may result in non‑coverage.

Single‑gene testing for CLCN1 (myotonia congenita) and for CACNA1S/SCN4A (periodic paralysis) — or a Periodic Paralysis multigene panel — is considered medically necessary only when the specific clinical features and documentation requirements in the policy are met. Testing for these genes or panels is investigational (not covered) for indications that do not meet the listed clinical criteria.

When molecular testing is appropriate and expected to establish the diagnosis (for example, DMD or myotonic dystrophy), the policy indicates that muscle biopsy should not be performed as a first‑line diagnostic test. The recommended diagnostic sequence prioritizes targeted molecular testing (deletion/duplication and sequencing or repeat analysis) before considering muscle biopsy.

D4Z4 Haplotype Analysis and related SMCHD1/DNMT3B testing were removed from the Policy Reference Table in the most recent updates. The removal implies these tests are no longer listed in the policy’s reference table of example tests, and users should consult the payer platform for the current test registry and coverage status.

Definitions & Key Terms

Diagnostic genetic testing definition

DefinitionGenetic testing used to establish or confirm a diagnosis in a patient with signs and/or symptoms of a genetic disorder when clinical evaluation and other standard laboratory tests/imaging have been non-diagnostic or inconclusive.

PurposeConfirming a genetic diagnosis may inform clinical management and/or eliminate the need for further diagnostic workup.

ScopeApplies to genetic testing for hereditary epilepsy, neurodegenerative, and neuromuscular genetic diseases addressed in this policy.

Comprehensive neuromuscular panel definition

DefinitionMultigene panel testing (example CPTs: 81161, 81404, 81405, 81406, 81479) to establish a genetic diagnosis for neuromuscular disorders when specified clinical criteria are met or prior targeted testing was non-diagnostic.

Eligibility Requirements & Preconditions

Genetic testing under this policy is intended to establish or confirm a diagnosis for individuals with signs and/or symptoms of hereditary epilepsy, neurodegenerative, or neuromuscular disorders when standard clinical evaluation and other laboratory or imaging studies are non‑diagnostic. Documentation must show the clinical rationale and how testing will inform management or avoid further unnecessary workup.

Some tests require explicit exclusion of alternative, non‑genetic causes prior to testing. For example, periodic paralysis testing requires exclusion of non‑genetic causes of hypokalemia, and Friedreich ataxia criteria require that non‑genetic causes of ataxia have been ruled out. The policy lists examples of conditions that should be considered and documented before genetic testing is approved.

Several indications require a compatible family history to meet criteria. Tests such as NOTCH3 (CADASIL) and PSEN1/PSEN2/APP (early‑onset Alzheimer disease) require a family history consistent with autosomal dominant inheritance or an affected close relative in the scenarios described. The policy defines close relatives and describes when family history supports coverage.

The policy consistently references family history when appropriate: many tests require either an autosomal dominant pattern in the family or a close affected relative to support testing in asymptomatic individuals or to establish testing priority. Where familial testing is central, the criteria indicate testing of the affected family member is preferred when available.

For some conditions (for example, Friedreich ataxia), the policy requires exclusion of alternative non‑genetic causes of the phenotype (e.g., acquired causes of ataxia such as alcoholism, vitamin deficiency, MS, vascular disease, tumors). Documentation that non‑genetic causes were considered and excluded is required to meet medical necessity.

Background & Supporting Evidence

Genetic testing is used to establish or confirm diagnoses in symptomatic patients when standard evaluation is inconclusive; a confirmed genetic diagnosis can guide management, enrollment in trials, and counseling, and may obviate additional invasive testing. The background supports using molecular testing as first‑line for several disorders when clinical suspicion is high.

For suspected inherited neuromuscular and neurodegenerative disorders the policy endorses targeted molecular approaches: deletion/duplication testing for DMD (MLPA or CGH array) as first‑line, repeat expansion testing for myotonic dystrophy as first‑line, and reflex sequencing when indicated. These diagnostic pathways align with specialty guidance cited in the policy and are expected to replace routine first‑line muscle biopsy in many scenarios.

GeneReviews guidance for hereditary spastic paraplegia is cited to support use of a multigene panel as a cost‑effective primary testing strategy. The policy reflects that a targeted multigene panel is likely to identify the genetic cause while limiting variants of uncertain significance compared with broader testing in many cases.

The policy added enumerated clinical signs for congenital myasthenic syndromes (neonatal respiratory insufficiency, joint contractures, stridor, feeding difficulties, ptosis, facial/bulbar weakness, abnormal EMG, delayed milestones) to clarify when a congenital myasthenic syndromes panel is appropriate and to support documentation requirements for medical necessity.

The diagnostic evaluation overview emphasizes condition‑specific testing pathways: use multigene panels for limb‑girdle muscular dystrophy and hereditary spastic paraplegia, prioritize deletion/duplication and sequencing for dystrophinopathies, and use targeted repeat testing for repeat expansion disorders (FXN, HTT, DMPK/CNBP). These approaches are consistent with professional society guidance and GeneReviews summaries cited in the policy.

Revision History & Policy Changes

2024-04revision

Semi-annual review: coding, reference table, background and references updated; added Periodic Paralysis Multigene Panel to CACNA1S/SCN4A titles and criteria; replaced 'coverage criteria' wording across policy and updated numerous panel titles (e.g., Neuromuscular NGS Panel to Comprehensive Neuromuscular Disorders Panel) and additions such as Rett syndrome and CADASIL.

(multiple revisions reflected 03/23–04/24)wording_edit

Extensive wording edits emphasizing criteria/panel content (e.g., replacing 'coverage criteria' with 'criteria', adding/clarifying enumerated clinical features) focused on clarifying indications and panel inclusions rather than introducing explicit blanket denials.

2024-11-24

Policy Summary

PayerCentene

PolicyConcert Genetic Testing: Epilepsy, Neurodegenerative, and Neuromuscular Disorders

Policy CodePolicy N/A

Change TypeCriteria revisions & additions

Effective DateN/A

Next Review DateN/A

Key ActionVerify clinical documentation and prior authorization requirements (including age, symptomatic, and prior testing criteria) when ordering genetic testing.

SourceLink

On This Page

Prior Authorization

MECP2 Testing — Prior Authorization Required

MECP2 sequencing and deletion/duplication analysis requires prior authorization and is medically necessary only when clinical criteria for Rett syndrome are met (developmental regression in the specified age ranges, plus ≥1 listed features, and exclusion of alternate causes). Testing outside these criteria is investigational.

Codes cited (e.g., 0234U, 81302, 81304) are provided for reference — confirm coding guidance prior to submission (chunk 3)

Prior Authorization

PSEN1/PSEN2/APP Testing — Prior Authorization & Counseling Required

PSEN1, PSEN2, and APP sequencing and deletion/duplication analyses have specific prior authorization requirements and age/clinical restrictions. Testing is medically necessary only for the defined scenarios related to early‑onset Alzheimer disease (including asymptomatic adults with autosomal dominant family history and symptomatic individuals meeting the age/family history criteria). Predictive testing requires thorough pre‑ and post‑test counseling. Testing outside these criteria or other Alzheimer genes is investigational.

APOE variant analysis has separate, limited indication (see APOE callout) (chunks 38, 39)
Confirm codes (e.g., 81405, 81406, 81479) before billing (chunk 3)

Prior Authorization

APOE Testing — Limited Prior Authorization for Monoclonal Antibody Treatment Evaluation

APOE variant analysis is limited and requires prior authorization when used to evaluate suitability for monoclonal antibody therapy for Alzheimer disease (e.g., Leqembi, Kisunla). APOE testing for other indications is investigational and may be denied.

Codes noted (81401, 81479, S3852) are informational — verify current coding and plan‑specific prior authorization requirements (chunks 3, 39)

Documentation Required

Use of Multigene Panels — Authorization & Documentation Expectations

Use of multigene panels is appropriate when the clinical presentation is not consistent with a single‑gene disorder or when prior targeted/single‑gene testing was non‑diagnostic. For many neuromuscular and LGMD presentations, a recommended strategy is to start with a disease‑specific targeted test (e.g., DMD deletion/duplication) when clinically indicated, then proceed to sequencing or broader panels if negative. Document prior testing and rationale for panel testing.

Document prior targeted/single‑gene testing and non‑diagnostic results when requesting multigene panels (chunks 30, 31)
Verify panels/codes (e.g., 81161, 81404–81406, 81479) and obtain prior authorization as required (chunk 3, 30)

Prior Authorization

Prior Authorization / Medical Review for Selected Tests — Documentation Required

Selected tests and panels are subject to prior authorization and/or medical review. Prior authorization requires submission of supporting clinical documentation that demonstrates the member meets the specific clinical criteria (symptoms, age at onset, family history, prior testing results, laboratory or imaging findings) outlined in the policy. Plan coverage documents govern final authorization and payment decisions.

Provide documentation of listed clinical features (e.g., neonatal signs, abnormal CK, EMG findings, documented serum potassium during attacks, age at onset, wheelchair timing) when requesting authorization (chunks 30, 41, 42, 54, 55)
Include prior targeted testing results (non‑diagnostic) when applicable (chunk 31)
Verify that codes cited in the policy are informational and confirm current coding guidance before claim submission (chunk 3)

Denial Risk

Investigational Indications — Denial Risk

Investigational indications may trigger denial. Tests labeled investigational in the policy (including panels or gene tests when criteria are not met) are not covered and may be denied if documentation does not support a medically necessary indication.

Examples of investigational uses that risk denial: comprehensive neuromuscular panel for indications not meeting criteria; comprehensive ataxia panel for non‑listed indications; CACNA1S/SCN4A and periodic paralysis panels for non‑specified indications; CLCN1 testing for indications other than specified myotonia features; PSEN1/PSEN2/APP testing for other indications (chunks 31, 54, 55, 36, 37, 131)
Providers should supply clinical justification that meets policy criteria to avoid denial (chunks 31, 54, 55)

Documentation Required

Clinical Justification Required — Provide Objective Findings

Clinical justification is required — testing should be performed only after a non‑diagnostic standard evaluation and must include documentation of the clinical findings that meet the policy criteria. Requests lacking sufficient clinical documentation (age/symptom criteria, laboratory values, imaging, family history, prior testing) may be denied.

Be explicit about age and symptom criteria (e.g., DMD onset age, wheelchair timing, CK levels) and include objective data (e.g., EMG, CK, serum potassium during attacks) (chunks 41, 42, 54, 55)
Document exclusion of alternative causes where required (e.g., non‑genetic causes of ataxia, causes of hypokalemia) (chunks 31, 55)

Documentation Required

Clinical Findings Required for Neuromuscular Panels — Document Specific Features

For neuromuscular panels, document the specific clinical findings that meet the policy (neonatal respiratory issues, joint contractures, feeding difficulties, abnormal fatigability, delayed milestones, ptosis/extraocular weakness, elevated CK, abnormal EMG, etc.). Panels are medically necessary only when the presentation is inconsistent with a single‑gene disorder or prior targeted testing was non‑diagnostic.

List the specific signs/symptoms present in the member and attach supporting documentation (clinic notes, EMG report, lab results) (chunk 30)
If prior targeted testing (e.g., SMN1, DMD, PMP22) was performed, include the test performed, lab, date, and non‑diagnostic result (chunk 31)

Documentation Required

Prior Testing Documentation — Required When Specified

Prior targeted/single‑gene testing results must be documented when required by the policy (e.g., if panel coverage is conditional on prior non‑diagnostic testing). Include the name of the test, laboratory, date, and result. Lack of prior testing documentation when required may result in denial.

Examples: DMD deletion/duplication testing by MLPA or CGH followed by sequencing if negative (chunks 73, 41, 42)
Document prior single‑gene testing for SMN1, DMD, PMP22 when applicable (chunk 31)

Documentation Required

DMD/BMD — Required Clinical Documentation & Testing Pathway

DMD/BMD testing requests must include required clinical documentation: age at symptom onset, timing of wheelchair dependency, serum creatine kinase concentrations, and the specific clinical features of DMD or BMD as listed. Use the recommended diagnostic pathway (deletion/duplication testing first, then sequencing if negative) and document prior test results.

Provide CK values (typically >10× normal for DMD, >5× for BMD), age at onset, and wheelchair dependency timing when requesting testing (chunks 41, 42)
If deletion/duplication testing was negative, include those results before requesting sequencing (chunks 73, 41)

Documentation Required

Periodic Paralysis — Documentation Required

For periodic paralysis testing, document exclusion of alternative causes of hypokalemia and provide documentation of attacks with serum potassium measurements. Meeting the listed attack criteria or constellation of features is required before genetic testing will be authorized.

Provide serum potassium values from affected attacks and documentation that renal, adrenal, thyroid causes and diuretic/laxative abuse were excluded (chunks 55, 95)
If only one documented attack, include family history of a similar documented attack (chunk 55)

Documentation Required

Myotonia (CLCN1) — Documentation Required

For myotonia (CLCN1) testing, document clinical myotonia features such as episodes of muscle stiffness beginning in childhood, percussion‑elicited myotonia, or EMG demonstrating myotonic bursts. CLCN1 testing is investigational for indications outside these specified features.

Include EMG reports when available and describe percussion myotonia or clinical history of exercise‑improved stiffness (chunks 54, 92)

Documentation Required

Diagnostic Testing Pathway — Document Prior Steps & Results

Document the diagnostic testing pathway used (e.g., prior targeted tests, sequencing after negative deletion/duplication, use of disease‑specific panels), and attach prior test reports. Failure to document the stepwise diagnostic approach when required by the policy may delay or prevent authorization.

Attach prior deletion/duplication results (MLPA/CGH) before requesting sequencing for DMD when applicable (chunks 73, 41)
For suspected LGMD, document rationale for choosing a broad neuromuscular panel (chunk 84)

Note

Supporting Documentation — Use of Guideline & GeneReviews Evidence

Supporting documentation and expert guidance (e.g., GeneReviews, ACMG, professional society guidance) are cited as background and should be used to support clinical necessity arguments in authorization requests. Include relevant guideline references or summaries when available.

Cite or attach pertinent GeneReviews or society guideline excerpts when they directly support the requested test (chunks 73, 77, 92, 95)

Documentation Required

Counseling Prerequisite for Predictive Testing — Documentation Required

Predictive and presymptomatic testing (including predictive testing for adult‑onset conditions) should only be performed after thorough pre‑ and post‑test counseling. Many predictive tests have age or symptom prerequisites; failure to meet age/symptom criteria or absence of counseling may be grounds for denial.

Document that counseling was provided and that the member meets age/symptom criteria (e.g., predictive testing of minors discouraged; HTT predictive testing requires age ≥18) (chunks 45, 77, 111)
Requests for predictive testing lacking counseling documentation may be returned or denied (chunks 38, 45)

Close relatives definition

DefinitionClose relatives include first-, second-, and third-degree blood relatives on the same side of the family (first-degree: parents, siblings, children; second-degree: grandparents, aunts/uncles, nieces/nephews, grandchildren, half-siblings; third-degree: great-grandparents, great-aunts/uncles, first cousins, etc.).

Use in criteriaClose relative definitions are referenced across criteria (e.g., HTT predictive testing, DMD/BMD asymptomatic carrier testing, periodic paralysis family-history rules).

Example relevanceOne attack in a proband plus one attack in a close relative with documented low potassium can meet hypoPP criteria per policy.

GeneReviews explanation and citation practice

Role of GeneReviewsGeneReviews is an expert-authored, peer-reviewed online resource summarizing current literature on genetic diseases and testing recommendations; cited as supporting clinical background in this policy.

Citation practicePolicy references GeneReviews entries and their version/date (e.g., V1.2025, Date of Last Revision 11/24) as supporting documentation for clinical criteria and testing strategies.

Use in documentationGeneReviews summaries are noted as examples of supporting documentation that can justify testing decisions to meet policy criteria.

Periodic Paralysis Multigene Panel — newly added to CACNA1S/SCN4A options

Change summaryPeriodic Paralysis Multigene Panel was added as an option to CACNA1S/SCN4A sequencing criteria and title (policy update).

Testing optionsPolicy allows CACNA1S and/or SCN4A sequencing or a Periodic Paralysis Multigene Panel for appropriate clinical presentations when alternative causes excluded and attack criteria met.

Documentation requirementRequests must document exclusion of alternative causes of hypokalemia and attacks with documented serum potassium <3.5 mEq/L when applicable.

Diagnostic DMD testing — differentiated from prenatal versions

Definition distinctionDiagnostic DMD testing refers specifically to sequencing and/or deletion/duplication analysis performed to establish or confirm DMD/BMD; policy distinguishes diagnostic testing from prenatal versions.

Testing sequenceFirst-line: MLPA or comparative genomic hybridization array for deletions/duplications; second-line: sequencing if negative; muscle biopsy if genetic testing is nondiagnostic.

Coding examplesExample CPTs associated with diagnostic DMD testing include 0218U, 81161, and 81408 as listed in policy sections.

Clinical policy definition

DefinitionClinical policy: a guide to medical necessity used to assist coverage decisions and administer benefits; it does not constitute medical advice or dictate clinical practice.

Provider responsibilityProviders are expected to exercise professional medical judgment and are responsible for diagnosis and treatment decisions; the policy does not replace clinical judgment.

Coverage precedenceState Medicaid coverage provisions take precedence over this clinical policy when conflicts exist; providers should refer to state Medicaid manuals and plan documents for specifics.