ModifiedAmbetter NevadaPolicy N/A

Genetic and molecular testing for neurological conditions

This policy addresses use and coding implications of laboratory genetic and molecular tests (panels and single-gene assays) for evaluation of neurological conditions; it informs providers about referenced CPT/ICD codes and example panels and affects providers submitting claims and ordering/testing labs for Ambetter Nevada members.

Policy Summary

PayerAmbetter Nevada

PolicyGenetic and molecular testing for neurological conditions

Policy CodePolicy N/A

Change TypeMultiple wording revisions and material criterion adjustments (age limits, title updates, removals of minimum gene lists)

Effective DateN/A

Next Review DateN/A

Key ActionProviders should reference up-to-date professional coding guidance prior to claim submission.

SourceLink

POLICY UPDATE CHANGES

Age restriction for HTT repeat analysis added (testing limited to 18 or older) and multiple panel titles and criterion wording were revised; numerous non-clinical wording and title updates recorded.

APOE variant analysis updated to evaluate suitability for monoclonal antibody therapy and added diagnostic criterion for Alzheimer's disease; test names in the policy reference table updated.

Removed minimum gene list requirement for PMP22 sequencing/deletion/duplication analysis or multigene panel.

multiplePanels referenced

manyCPT examples

70%

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.

DMD deletion/duplication yield

20%Diagnostic yield (Winder et al)

03/23 & 10/23Revision/approval dates cited

Coverage Criteria for Genetic and Molecular Testing

Coverage and coding disclaimer

Codes referenced in this policy are informational; inclusion or exclusion does not guarantee coverage.

Codes referenced are for informational purposes only; inclusion or exclusion of any codes does not guarantee coverage.

Providers should reference the most up-to-date professional coding guidance prior to claim submission.

Referenced test examples

Examples of tests and panels referenced in this policy (not exhaustive):

Comprehensive Neuromuscular Disorders Panel (example billing codes: 81161, 81404, 81405).

Epilepsy Multigene Panel / Comprehensive Epilepsy Panel (example billing codes: 81185, 81189, 81406, 81419, 81479).

MECP2 sequencing and deletion/duplication analysis (example tests: MECP2 Full Gene Sequencing & Del/Dup).

SMN1 sequencing and SMN2 deletion/duplication analysis (SMA testing; referenced for newborn screening confirmation).

FXN repeat analysis (Friedreich ataxia) and HTT CAG repeat analysis (Huntington disease).

Ataxia-related genetic testing

Covered when ALL of the following are met:

ALL of the following

Clinical suspicion (need one of)
- Progressive gait and limb ataxia (cerebellar ataxia)
- Dysarthria
- Decrease or loss of position and/or vibration sense in lower limbs
- Pyramidal weakness of the legs
- Extensor plantar responses/Babinski signs

HTT Repeat Analysis

HTT repeat analysis is considered medically necessary when ONE of the following applies:

ANY of the following

The individual displays clinical features of Huntington disease (progressive motor disability featuring chorea).
The individual has a clinical diagnosis of Huntington disease.
Predictive testing conditions
- The individual is presymptomatic/asymptomatic.
- The individual is 18 years of age or older.
- Either the individual has a close relative with HTT CAG repeat expansion (≥27 repeats) OR the individual has a first-degree relative with a clinical diagnosis of HD without prior genetic testing.

Movement disorder and neuromuscular criteria

Multigene panel testing is considered medically necessary for the following movement disorder and neuromuscular presentations when clinical features are consistent:

Hereditary dystonia panel: clinical presentation consistent with dystonia or patterns of abnormal repetitive dystonic movements (Hereditary Dystonia criteria).

Parkinson's disease panel: clinical diagnosis of Parkinson disease AND a family history of Parkinson disease.

Hereditary spastic paraplegia panel: presence of lower-extremity spasticity and/or weakness, hyperreflexia or extensor plantar responses, and impaired vibration in distal lower extremities.

Congenital myasthenic syndromes panel: neonatal respiratory insufficiency, neonatal joint contractures, stridor, feeding difficulties, poor suck/cry, fatigable weakness, delayed milestones, ptosis, facial/bulbar weakness, spinal deformity, or abnormal EMG consistent with CMS.

CLCN1 testing (myotonia congenita): episodes of muscle stiffness/myotonia beginning in early childhood; percussion or EMG characteristic myotonic bursts.

Miscellaneous covered disorders

Genetic testing for the following disorders is considered medically necessary when clinical features are consistent with the disorder:

AADC deficiency; Hereditary transthyretin amyloidosis; X-linked adrenoleukodystrophy; L1 syndrome; SCN9A neuropathic pain syndromes; familial cerebral cavernous malformation; STAC3 disorder (testing appropriate when clinical presentation matches disorder).

All other epilepsy, neurodegenerative, and neuromuscular disorders not specifically listed will be evaluated using the 'General Approach to Laboratory Testing' criteria.

Clinical feature resources cited include GeneReviews, OMIM, Genetics Home Reference, or other scholarly sources for disorder-specific features.

SMA testing

SMN1/SMN2 testing is recommended in newborn screening follow-up and symptomatic individuals:

ALL of the following

Newborn screen positive for SMA (realtime PCR detecting common SMN1 deletion) should have follow-up molecular confirmation.
Symptomatic individuals with atypical later-onset SMA or infantile-onset SMA without prior treatment: single-gene SMN1 testing or a multigene panel that includes SMN1 and SMN2 is appropriate.
SMN2 copy number (deletion/duplication analysis) may be performed to provide additional clinical correlation when SMA diagnosis is confirmed.

SMA testing criteria

Indications and clinical features that support SMN1/SMN2 testing:

Positive newborn screen for SMA requiring confirmatory molecular testing (SMN1 deletion detection recommended).

Symptomatic individuals with atypical later-onset SMA or untreated infantile-onset SMA: perform SMN1 single-gene testing or multigene panel including SMN1 and SMN2.

Clinical features supporting testing include history of motor difficulties with loss of skills, proximal>distal weakness, hypotonia, areflexia/hyporeflexia, tongue fasciculations, hand tremor, recurrent early respiratory infections, and EMG evidence of motor unit disease.

MECP2 testing criteria

MECP2 testing should be considered for females with characteristic clinical regression and associated features:

Females with regression beginning between ages ~1–4 years followed by recovery or stabilization, plus loss of hand skills or spoken language, gait abnormalities, and stereotypic hand movements — consider MECP2 sequencing and deletion/duplication analysis.

Exclude alternative explanations such as perinatal brain injury, neurometabolic disease, or severe infection, and grossly abnormal development in the first six months of life.

Epilepsy testing criteria

Epilepsy genetic testing guidance (first-tier recommendations):

Individuals with unexplained epilepsy should be offered genetic testing regardless of age; multi-gene comprehensive testing (exome/genome or multigene panel) is strongly recommended as first-tier.

Recommended panels should have a minimum of 25 genes and include copy number analysis; panels with fewer than 25 genes may be considered only in rare situations with alternate criteria.

Alzheimer's testing criteria

Alzheimer's-related testing considerations and therapy-related testing:

PSEN1/PSEN2/APP sequencing is offered for symptomatic individuals with early-onset Alzheimer disease (EOAD), particularly with family history or when a relative has a pathogenic mutation; pediatric and routine prenatal testing not advised.

APOE e4 testing is recommended prior to initiation of certain anti-amyloid monoclonal antibody therapies (per FDA labels) due to increased ARIA risk in e4 homozygotes; APOE variant analysis language was updated to assess suitability for monoclonal antibody therapy and diagnostic considerations for Alzheimer's disease.

ALS testing criteria

ALS genetic testing recommendations:

All persons with ALS should be offered a gene panel that includes C9orf72, SOD1, FUS, TARDBP and other ClinGen-definitive ALS genes; clinical diagnostic criteria (UMN and LMN signs, progressive spread, exclusion of other causes) should be met.

If an affected family member is available, testing that relative first is ideal; asymptomatic persons interested in testing should receive counseling about low likelihood of informative result.

Dystrophinopathy testing criteria

Dystrophinopathy testing workflow and clinical triggers:

Perform deletion/duplication testing (MLPA or comparative genomic hybridization array) first because ~70% of DMD cases have exon deletions/duplications; if negative, proceed to sequencing for point mutations (~25–30%).

Suspect DMD with progressive proximal>distal symmetric weakness, symptoms before age 5, wheelchair dependency before age 13, and CPK >10× normal; suspect BMD with later onset features and CPK >5× normal.

FSHD testing criteria

FSHD testing recommendations:

Genetic testing can confirm FSHD1 via identification of a heterozygous pathogenic contraction of the D4Z4 repeat on a permissive chromosome 4 haplotype; if negative, pursue testing for FSHD2 (SMCHD1/DNMT3B) or other myopathies, especially in atypical or sporadic cases.

Suspect FSHD with weakness predominantly of facial, scapular stabilizer, or foot dorsiflexor muscles (often asymmetric), progression after pregnancy, refractory inflammatory myopathy, or family history.

FXN testing criteria

FXN (Friedreich ataxia) testing indications:

Suspect Friedreich ataxia with typical neurologic signs (onset usually before 25), progressive gait and limb ataxia, dysarthria, loss of position/vibration sense, pyramidal signs, cardiomyopathy, pes cavus, endocrinologic features, optic atrophy/deafness, and compatible family history; exclude non-genetic causes.

Concert interprets 'combination' of clinical features to mean at least two features for suspicion of FRDA.

HTT testing criteria

HTT testing guidance (symptomatic and predictive testing):

HTT CAG repeat analysis is appropriate for symptomatic individuals with progressive chorea, cognitive decline, or family history suggestive of autosomal dominant inheritance; confirmatory testing is offered at or after clinical diagnosis.

Predictive/asymptomatic testing is limited to individuals aged 18 years or older and requires thorough pre- and post-test counseling; predictive testing of minors is generally discouraged unless medically indicated.

PMP22 testing criteria

PMP22 testing criteria for peripheral neuropathy/HNPP/CMT presentations:

Consider PMP22 sequencing and/or deletion/duplication analysis or multigene panel when individuals present with one or more of: distal weakness/atrophy; pes cavus; weak ankle dorsiflexion; depressed reflexes; recurrent focal neuropathies at entrapment sites; painless nerve palsy after minor trauma; exam evidence of prior nerve palsy; complete spontaneous recovery from neuropathies.

HNPP diagnosis established by identification of the 1.5‑Mb recurrent deletion (~80% of cases) or a PMP22 sequence variant (~20%) via molecular testing.

Disease-specific testing criteria and rationale

Disease-specific indications and clinical features cited to support use of genetic testing or panels:

Charcot-Marie-Tooth (CMT): symmetric distal motor neuropathy with distal weakness/atrophy and pes cavus; genetic diagnosis can aid prognosis and counseling.

HNPP: recurrent focal neuropathies, painless nerve palsies after minor trauma; diagnosis by 1.5‑Mb recurrent deletion or PMP22 sequence variant.

Limb-Girdle Muscular Dystrophy (LGMD): slowly progressive symmetrical weakness; multigene panel testing preferred over muscle biopsy.

Myotonic Dystrophy Type 1 (DM1): molecular testing first-line; >50 CTG repeats diagnostic; muscle biopsy not required when clinical suspicion exists.

Myotonic Dystrophy Type 2 (DM2): DNA-based testing first-line; >75 CCTG repeats diagnostic; 28–75 repeats considered gray zone; tissue testing or segregation may help.

Selected revised coverage criteria examples

Examples of notable revisions to coverage criteria in this update:

HTT repeat analysis: age restriction added — testing restricted to individuals 18 years or older for predictive testing contexts.

PSEN1/PSEN2/APP: clarified symptomatic age requirement for early-onset Alzheimer's disease (EOAD) references; additional wording updated to aid rapid medical review.

PMP22 criteria: removed minimum gene list requirement for PMP22 sequencing/deletion-duplication analysis or multigene panel.

APOE variant analysis: language updated to assess suitability for monoclonal antibody therapy; added diagnostic considerations and example therapy (Kisluna).

Comprehensive Neuromuscular Disorders Panel: criteria rephrased to require 'at least one of the following' with enumerated clinical features for clarity.

Application and precedence notes

Important application and precedence notes:

This clinical policy is a guide to medical necessity to assist in coverage decisions and administering benefits; it does not constitute a contract or guarantee of payment or results.

Coverage decisions and administration of benefits are subject to plan documents, state and federal requirements, and applicable Health Plan-level administrative policies and procedures; when Medicaid or Medicare provisions conflict, respective manuals/NCDs/LCDs take precedence.

Providers retain independent medical judgment; this policy is not intended to dictate medical care.

Coding and CPT/ICD References

Example CPT codes referencedCPT

81161	Example comprehensive panel code referenced
81404	Example sequencing/deletion-duplication code referenced
81405	Example sequencing code referenced

Repeat expansion / gene-specific codesCPT

81271	HTT repeat analysis (Huntington)
81284	FXN related testing (Friedreich ataxia)

Ataxia & related genetic testsmixed

D4Z4 haplotype analysis; SMCHD1 and DNMT3B sequencing; FXN repeat analysis referenced

Spinal Muscular Atrophy testingmixedCovered

SMN1 sequencing and/or deletion/duplication analysis and SMN2 copy number determination (recommended for diagnosis and newborn screening confirmation)

DMD testingmixedCovered

Deletion/duplication testing by MLPA or comparative genomic hybridization array recommended as first confirmatory test for DMD; sequencing if negative

Panels renamed/retitledmixed

No codes listed

Policy reference table updatesmixed

Example test name updates in Policy Reference Table (e.g., APOE variant analysis, DMD example test name updates)

Coding informational note

Scope of listed codesCPT codes and descriptions included in this policy are for informational purposes only and are not intended to be all‑inclusive.

No coverage impliedInclusion or exclusion of any code in this policy does not guarantee coverage or non‑coverage.

Provider responsibilityProviders must reference the most up‑to‑date professional coding guidance prior to claim submission.

Reference to current manualsCPT codes and descriptions are from the current AMA manuals and are copyrighted material.

Age threshold for predictive HTT testing

Provider Requirements, Documentation, and Workflow

Documentation Required

Coding guidance and claim submission note — reference up-to-date professional coding guidance prior to claim submission

This policy references current professional coding guidance. Providers must reference the most up-to-date sources of CPT, ICD, and other coding guidance prior to claim submission. Inclusion or exclusion of any codes in this policy does not guarantee coverage.

Providers should verify codes against current CPT/ICD manuals and payer billing rules before submitting claims.
Tests and codes listed are informational and not exhaustive.

Documentation Required

Clinical eligibility and counseling requirements; Predictive testing restrictions

Genetic testing for the listed neuromuscular and neurologic conditions requires clinical documentation of eligibility and evidence that non-genetic causes have been considered or excluded where specified. Predictive (presymptomatic) testing is restricted and should only be offered following thorough pre- and post-test genetic counseling. For Huntington disease (HTT) predictive testing, individuals must be presymptomatic/asymptomatic and at least 18 years old and meet family-history criteria (close relative with CAG expansion ≥27 in HTT or a first-degree relative with clinical HD without prior genetic testing). For other disorders, follow the condition-specific criteria below and local policy for predictive testing.

Definitions and Scope

Neurological genetic/molecular tests

DefinitionGenetic and molecular tests used to evaluate neurological conditions, including single‑gene assays and multigene panels.

PurposeIntended to establish or confirm diagnoses of epilepsy, neuromuscular, and neurodegenerative disorders to guide management.

Scope noteTests discussed across the policy include example panels and single‑gene tests; the list is not exhaustive.

CPT coding note

CPT guidanceCPT codes and descriptions cited in this policy are informational — providers must use current coding guidance when billing.

Not all‑inclusiveCodes included are not intended to be all‑inclusive; see current AMA CPT manuals for authoritative coding.

Policy Summary

PayerAmbetter Nevada

PolicyGenetic and molecular testing for neurological conditions

Policy CodePolicy N/A

Change TypeMultiple wording revisions and material criterion adjustments (age limits, title updates, removals of minimum gene lists)

Effective DateN/A

Next Review DateN/A

Key ActionProviders should reference up-to-date professional coding guidance prior to claim submission.

SourceLink

On This Page

Hypertrophic nonobstructive cardiomyopathy

Glucose intolerance or diabetes mellitus

Optic atrophy and/or deafness

At least two of the listed clinical features are present (per Concert interpretation).

Non-genetic causes of ataxia have been ruled out (e.g., alcoholism, vitamin deficiencies, MS, vascular disease, tumors).

Predictive testing should be performed only with thorough pre- and post-test counseling; predictive testing of minors is generally discouraged unless medically indicated (defer when results do not impact childhood medical management).

Periodic paralysis panel (CACNA1S/SCN4A)

Alternative causes of hypokalemia have been excluded (renal, adrenal, thyroid dysfunction; renal tubular acidosis; diuretic/laxative abuse).
Two or more attacks of muscle weakness with documented serum potassium <3.5 mEq/L OR one attack plus a close relative with an attack with K+ <3.5 mEq/L OR three or more supportive clinical/laboratory features (onset in first/second decade; attacks >2 hours; triggers; improvement with potassium; family history; positive long exercise test).

Hereditary dystonia and Parkinson disease: GeneReviews and literature support multigene testing when clinical features/family history warrant testing and for research/trial eligibility.

Congenital Myasthenic Syndromes (CMS): neonatal and childhood presentations described; multigene panels referenced for diagnosis.

Myotonia congenita (CLCN1): genetic testing is gold standard; EMG is supportive; no consensus clinical diagnostic criteria published.

Hypokalemic periodic paralysis (CACNA1S/SCN4A): consensus diagnostic criteria require documented serum potassium <3.5 mEq/L for attacks and exclusion of other causes; when criteria met, multigene panel recommended.

Predictive HTT testing age limitPredictive (presymptomatic) HTT repeat testing is limited to individuals 18 years of age or older.

Context for predictive testingPredictive testing applies to presymptomatic/asymptomatic individuals undergoing predictive evaluation.

Counseling requirementPredictive testing should only be performed with thorough pre‑ and post‑test counseling.

Serum potassium threshold — periodic paralysis

Serum potassium thresholdDocumented serum potassium less than 3.5 mEq/L during attacks is required to support periodic paralysis genetic testing.

Attack frequency criterionTwo or more attacks with documented K+ <3.5 mEq/L qualifies, or one attack plus a relative with a documented attack.

Exclusion of other causesAlternative causes of hypokalemia (renal, adrenal, thyroid dysfunction; renal tubular acidosis; diuretic/laxative abuse) must be excluded.

Epilepsy panel minimum genes

Minimum gene countRecommended minimum of 25 genes for an epilepsy multigene panel (panel should include copy number analysis).

First‑tier testingMulti‑gene comprehensive testing (exome/genome or multigene panel) is strongly recommended as first‑tier for unexplained epilepsy regardless of age.

Panels <25 genesPanels with fewer than 25 genes may be considered only in rare situations using alternate criteria.

DM1 repeat threshold

DM1 diagnostic thresholdMore than 50 CTG repeats in the DMPK gene (3' UTR) are considered diagnostic for myotonic dystrophy type 1 (DM1).

First‑line testMolecular genetic testing is recommended as the first‑line investigation for suspected DM1; muscle biopsy is not required when clinical suspicion is clear.

False‑negative cautionFalse‑negative results can occur; expert referral is recommended when results are discordant with clinical suspicion.

DM2 repeat threshold

DM2 diagnostic thresholdMore than 75 CCTG repeats in CNBP (ZNF9) are considered diagnostic for myotonic dystrophy type 2 (DM2).

Gray‑zone rangeRepeat sizes of 28–75 CCTG are considered a gray zone for DM2 and may require testing of other tissues or segregation studies.

First‑line testingDNA‑based molecular testing is the recommended first‑line investigation for suspected DM2; muscle biopsy should not be used when clinical suspicion is clear.

HTT testing age threshold

HTT testing age requirementHTT repeat analysis (Huntington disease testing) is limited to individuals 18 years of age or older for predictive testing and testing guidance reflects this age restriction.

Symptomatic testing contextHTT testing is appropriate for symptomatic individuals with clinical features of Huntington disease or a clinical diagnosis regardless of age considerations for predictive testing.

Counseling for predictive testingPredictive HTT testing must be performed with thorough pre‑ and post‑test counseling.

Documented clinical features and family history are required when indicated (see condition-specific criteria).
Predictive testing only after documented pre- and post-test counseling; include counselor/provider name and date in request.
Age restrictions (e.g., HTT ≥18 years) must be documented when applicable.

Documentation Required

Laboratory documentation for periodic paralysis testing — requirement to exclude alternative causes of hypokalemia and documented serum potassium thresholds

For hypokalemic periodic paralysis (hypoPP), laboratory documentation must demonstrate exclusion of alternative causes of hypokalemia (e.g., renal, adrenal, thyroid dysfunction; renal tubular acidosis; diuretic or laxative abuse) and at least one of the following: two or more attacks of muscle weakness with documented serum potassium <3.5 mEq/L; one attack with a close relative with documented serum potassium <3.5 mEq/L; or three or more supportive clinical/laboratory features (onset in first/second decade, prolonged attacks, known triggers, improvement with potassium, family history, positive long exercise test). When phenotypic and laboratory findings suggest hypoPP, a multigene periodic paralysis panel is the recommended testing approach.

Include serum potassium values with date/time relative to attack in documentation.
Document investigations performed to exclude alternate causes (lab results, medication list).
Include family member testing/results or family history when applicable.

Documentation Required

DMD testing workflow — perform deletion/duplication testing first (MLPA or CGH array); if negative proceed to sequencing (NGS) for point mutations

For Duchenne muscular dystrophy (DMD) evaluation, perform deletion/duplication testing of the DMD gene first (eg, MLPA or comparative genomic hybridization array) because ~70% of individuals have exon-level deletions/duplications. If deletion/duplication testing is negative and clinical suspicion remains, proceed to sequencing (eg, next-generation sequencing) to detect point mutations, small insertions or deletions. If molecular testing is nondiagnostic but clinical suspicion persists, consider muscle biopsy for dystrophin protein analysis (immunohistochemistry or western blot).

Document method and results of deletion/duplication testing (MLPA or CGH array) before proceeding to sequencing.
If sequencing is performed after negative deletion/duplication testing, provide rationale and prior test dates.
If molecular testing is negative and biopsy is performed, include reason for biopsy and dystrophin testing results.

Documentation Required

APOE testing before anti-amyloid therapy — APOE e4 testing recommended prior to initiation of certain monoclonal antibody treatments due to ARIA risk stratification

APOE e4 testing is recommended prior to initiation of certain anti-amyloid monoclonal antibody therapies (per FDA labeling) because APOE genotype (especially e4 homozygosity) is associated with higher risk of amyloid-related imaging abnormalities (ARIA). Document APOE testing and results in the medical record when treatment with these agents is planned.

Include APOE genotype (e.g., e4 carrier status) and date of test in authorization documentation when applicable.
If APOE testing is unavailable or declined, document clinical rationale and informed consent discussion.

Documentation Required

Consolidation of familial variant criteria — criteria for known familial variant tests moved to 'Genetic Testing: General Approach to Genetic and Molecular Testing' to consolidate requirements

Criteria for testing a known familial variant have been consolidated into the policy 'Genetic Testing: General Approach to Genetic and Molecular Testing.' When requesting testing for a known familial variant, reference that policy and include documented evidence of the familial pathogenic/likely pathogenic variant (test report or laboratory documentation) and relationship to the proband. Requests for targeted familial-variant testing must include the specific variant, laboratory that identified it, and confirmation that the variant segregates in the family as reported.

Attach copy of relatives' genetic test report showing the familial pathogenic/likely pathogenic variant.
Indicate proband's relationship to the relative with the known variant and provide pedigree information.
If the familial variant is reported only in a non-clinical source, provide confirmatory clinical laboratory documentation.

Predictive testing counseling note

Counseling requirementPredictive genetic testing should only be performed in the setting and context of thorough pre‑ and post‑test counseling.

HTT predictive specificsFor HTT predictive testing, individuals must be presymptomatic and meet age/family‑history criteria (e.g., age ≥18, close relative with CAG expansion).

Provider responsibilityProviders should ensure counseling is documented and the patient understands implications prior to predictive testing.

Scope for other disorders

Evaluation standardGenetic testing for epilepsy, neurodegenerative, and neuromuscular disorders not specifically covered in this policy will be evaluated using the General Approach to Laboratory Testing criteria.

Clinical feature resourcesClinical features for specific disorders may reference resources such as GeneReviews, OMIM, and Genetics Home Reference.

Not exhaustiveLists of disorders in this policy are not meant to be comprehensive; other disorders follow the general evaluation approach.

SMN1/SMN2 testing

SMN1 testing componentsSMN1 sequencing and deletion/duplication analysis are recommended for diagnosis and follow‑up confirmation of SMA (including newborn screen confirmation).

SMN2 copy numberSMN2 copy number determination by deletion/duplication analysis can provide additional clinical correlation when SMA is confirmed.

Newborn screening follow‑upPositive SMA newborn screen (real‑time PCR detection of common SMN1 deletion) should have confirmatory molecular genetic testing.

ALS genetic panel

Recommended genes for ALS panelsPanels should include targeted C9orf72 repeat testing plus multigene coverage of major ALS genes such as C9orf72, SOD1, FUS, and TARDBP.

Offer to all ALS patientsAll persons with ALS should be offered a genetic panel including the genes listed by ClinGen as strongly/definitive for ALS.

Clinical diagnostic criteriaTesting should be considered in the context of established ALS clinical diagnostic criteria (UMN/LMN signs, progressive spread, exclusion of other causes).

Hypokalemic periodic paralysis — diagnostic criteria

Primary diagnostic criteria (summary)Primary hypokalemic periodic paralysis diagnostic criteria include two or more attacks with K+ <3.5 mEq/L OR one attack in proband plus one in relative with K+ <3.5 mEq/L OR three or more specified clinical/laboratory features.

When to use panelWhen phenotypic and laboratory findings suggest hypoPP, use a multigene periodic paralysis panel (CACNA1S, SCN4A, etc.).

Exclude other causesDiagnosis requires exclusion of other causes of hypokalemia (renal, adrenal, thyroid dysfunction; RTA; diuretic/laxative abuse).

Childhood definition

Childhood definitionChildhood is defined as the period of development until the 18th birthday.

Usage contextThis definition is applied across policy criteria where age distinctions (e.g., neonate, child, adult) affect testing recommendations.

Related termsDefinitions section also defines neonate and close relatives for clinical criteria use.

Close relatives definition

Definition of close relativesClose relatives include first‑, second‑, and third‑degree blood relatives (examples provided: parents, siblings, children; grandparents, aunts/uncles; great‑grandparents, first cousins).

Clinical applicationClose relative definitions are used in criteria requiring family history (e.g., HTT predictive testing, periodic paralysis criteria).

Degree examplesFirst‑degree: parents/siblings/children; Second‑degree: grandparents/aunts/uncles/nieces/nephews/half‑siblings; Third‑degree: great‑aunts/uncles, first cousins.

Neonate definition

Neonate definitionNeonate is defined as a baby who is four weeks old or younger.

Clinical relevanceNeonate criteria are applied where panels specify neonatal presentations (e.g., limb‑girdle panel neonatal triggers, congenital myasthenic syndromes).

Distinction from childhoodNeonate is a subset of childhood (which extends until 18th birthday) used for specific early‑life testing criteria.

Comprehensive Neuromuscular Disorders Panel — defining features

Key clinical features listedComprehensive Neuromuscular Disorders Panel is defined by presence of at least one enumerated clinical feature such as neonatal respiratory insufficiency, neonatal joint contractures, feeding difficulties, abnormal muscle findings, ptosis, facial/bulbar involvement, spinal deformity, or abnormal electromyography.

Use casePanel intended for heterogeneous congenital and early‑onset neuromuscular presentations where one or more listed features are present.

Panel renaming notePanel titles and clinical itemization were reworded in the policy revisions to require 'at least one of the following' features for eligibility.

Health Plan — definition / attribution

Health Plan definition'Health Plan' refers to a plan that has adopted this clinical policy and is operated or administered, in whole or in part, by Centene Management Company, LLC or its affiliates.

Policy contextThe policy is developed by qualified professionals and reflects standards of medical practice current at time of approval.

No liability/guaranteeThe Health Plan makes no representations or guarantees regarding payment or results; coverage is subject to plan documents and legal requirements.

Clinical policy — purpose and limitations

Policy purposeThis clinical policy provides guidance on medical necessity to assist coverage decisions and administering benefits.

Not a contractIt does not constitute a contract, medical advice, or guarantee of payment or results.

Superseding rulesState/federal requirements and Health Plan documents govern coverage; legal/regulatory requirements take precedence if discrepant.