Prior authorization required for listed CPT codes

Prior authorization is required for the listed multigene panel and single-gene CPT codes and coverage is limited to clinically indicated situations per the disorder-specific criteria.

• Applies to CPT codes including 81400–81408, 81410, 81411, and 81479 as listed in the coding table.
• If a panel is performed, the appropriate panel CPT code (e.g., 81410, 81411) should be used.

Prior authorization for genetic panels is subject to coverage review

Genetic testing for the listed connective tissue disorders and heritable thoracic aortic disease (HTAD)—whether single-gene or multigene panels—is subject to coverage criteria and may require prior authorization per the payer's General Approach to Genetic and Molecular Testing.

• Panel testing should be guided by phenotype and GeneReviews/ACMG guidance.
• Multigene panels are recommended where phenotype/family history suggest HTAD (see GeneReviews Table 1).

Coding updates affect prior authorization

Certain multigene panel and single-gene tests in the coding/reference table were modified (individual CPTs listed rather than ranges); prior authorization requirements follow the policy's updated coding/reference table.

• Policy edits removed some prior grouped codes and replaced them with specific CPT listings—prior authorization must reference the current coding table.
• Providers should confirm the exact CPT code(s) submitted match the policy's coding list to ensure appropriate prior auth processing.

Operational and policy-change reminder (provider impact)

Providers should note policy updates may change coverage and authorization procedures; consult the current policy and payer resources for operational changes.

Panel‑first approach recommended (informational)

Multigene panels are recommended as a first‑line approach in many clinical scenarios where phenotype and family history suggest a hereditary connective tissue disorder or HTAD, consistent with GeneReviews and guideline recommendations (informational only).

• GeneReviews and ACMG guidance support use of multigene panels rather than serial single‑gene testing when clinical findings suggest disorders such as LDS or HTAD.
• This is informational and does not replace disorder‑specific medical necessity criteria in the policy.

Confirm current panel content and coding before ordering

Providers should verify coding and criteria details against the current policy when ordering, as prior panel configurations and minimum gene lists were revised; confirm test content meets policy expectations.

Document aortic root Z‑score, ectopia lentis, or systemic score for Marfan (FBN1) testing

For FBN1 testing to confirm Marfan syndrome, documentation must support aortic root enlargement (Z‑score ≥2) or dissection, ectopia lentis, or a systemic score ≥7 using the policy's listed systemic features.

• Aortic root enlargement is defined as a Z‑score ≥2, standardized to age and body size.
• If systemic score pathway is used, document the component features and point totals per the policy (≥7 required).

Document ≥2 LDS clinical features or qualifying family history

Documentation for Loeys‑Dietz testing must show the member meets at least two listed clinical features OR has a first‑degree relative with a clinical diagnosis of LDS.

• List qualifying features (e.g., characteristic facial features, bifid uvula/cleft palate, arterial tortuosity, aortic dilatation/dissection, joint hypermobility).
• If family history is used, document relation (first‑degree) and the relative's clinical diagnosis.

Document clinical aortic disease and AD family history for TAAD panels

For TAAD multigene panel coverage, document a history of aortic root enlargement, thoracic aneurysm, or type A/B aortic dissection, absence of diagnostic criteria for another connective tissue disorder, and a family history of dilation/dissection consistent with autosomal dominant inheritance.

• Include imaging or surgical reports documenting aortic enlargement/aneurysm/dissection.
• Document family history details consistent with autosomal dominant inheritance.

Document cEDS clinical features and panel gene content (COL5A1/COL5A2)

For classic EDS (cEDS) panel coverage, document skin hyperextensibility with atrophic scarring plus either generalized joint hypermobility or at least three listed supportive features, and confirm the panel includes at minimum COL5A1 and COL5A2.

• Supportive features include easy bruising, soft doughy skin, skin fragility, molluscoid pseudotumors, subcutaneous spheroids, hernia, epicanthal folds, complications of joint hypermobility, or first‑degree relative with clinical cEDS.
• Confirm test includes COL5A1 and COL5A2 in report or test order.

Document major/minor criteria or family history for vEDS (COL3A1) testing

For COL3A1 testing to evaluate vEDS, documentation must show one major criterion (e.g., arterial rupture/dissection <40 years, spontaneous sigmoid colon perforation, third‑trimester uterine rupture without prior C‑section, CCSF without trauma) or two or more minor criteria, or a close relative with clinical vEDS.

• Major features include arterial rupture/dissection <40 years, spontaneous sigmoid colon perforation, uterine rupture in third trimester without prior C‑section, or carotid‑cavernous sinus fistula without trauma.
• Minor features encompass bruising, thin translucent skin, characteristic facial appearance, spontaneous pneumothorax, tendon/muscle rupture, keratoconus, gingival fragility, early varicose veins, etc.

Provide clinical features and family history to support testing requests

Providers should include clinical details that support the requested genetic test: aortic root Z‑score, presence/absence of ectopia lentis, systemic score components, family history specifics, and major/minor criteria for EDS subtypes as relevant.

• Attach imaging, ophthalmology, surgical, or genetic family history documentation to the prior authorization or test order.
• Document rationale for single‑gene versus multigene panel selection based on phenotype and GeneReviews/ACMG guidance.

Include vEDS‑specific presenting features and plan for CNV testing when indicated

For vEDS testing specifically, include documentation of presenting features suggestive of vEDS (family history, arterial rupture/dissection <40 years, unexplained sigmoid colon rupture, spontaneous pneumothorax with other vEDS features) and the rationale for molecular testing of COL3A1 (and COL1A1 when relevant).

• If sequencing is negative, document plan or performance of CNV detection (deletion/duplication) to identify large deletions/duplications.
• Note that diagnosis rests on identification of a causative variant in one allele of COL3A1.

Indications outside specified criteria may be denied as investigational

Multigene panels and single‑gene tests performed for indications outside the policy's disorder‑specific medical necessity criteria (for example isolated hypermobility or evaluation solely for hEDS) are considered investigational and may be denied.

• hEDS is diagnosed clinically and genetic testing solely for hEDS is not appropriate per GeneReviews.
• Panel requests for indications not supported by the policy should be expected to be denied as investigational.

Testing outside disorder‑specific criteria may be denied

Testing performed outside the specified medical necessity criteria for each disorder (single‑gene or panel) may be denied as investigational; ensure requests meet the gene‑ or syndrome‑specific coverage nodes before ordering.

• Confirm the enrollee meets at least one qualifying node for the disorder being tested (e.g., Marfan, LDS, TAAD, cEDS, vEDS).
• Requests lacking documented criteria are at risk of denial.

Genetic testing solely for hEDS is not appropriate

Requests for genetic testing solely to evaluate for hypermobile Ehlers‑Danlos syndrome (hEDS) are not appropriate and may be denied because hEDS is diagnosed clinically and causative genes are currently unknown.

• Do not order genetic testing solely to evaluate hEDS; document alternative reasons if testing is requested (e.g., suspicion for another EDS subtype).

Missing vEDS clinical indication or complementary testing risks denial

Failure to document clinical features suggestive of vEDS (e.g., family history, arterial rupture/dissection <40 years, unexplained sigmoid colon rupture, spontaneous pneumothorax with other vEDS features) or failure to order appropriate COL3A1 sequencing and complementary CNV testing when indicated may lead to denial.

• Document major/minor criteria or family history when requesting COL3A1 testing.
• If sequencing is negative, document CNV testing or plan to perform deletion/duplication analysis.

Order testing in appropriate clinical context per GeneReviews/ACMG

Order genetic testing in the context of appropriate clinical evaluation and counseling per GeneReviews and ACMG recommendations; testing should be performed when clinical features and family history meet the policy criteria.

• GeneReviews and ACMG guidance support phenotype‑driven test selection and inform panel composition.
• Include pre‑test counseling as implied by guidance given testing implications for treatment and family recurrence risk.

Provide or document genetic counseling when ordering/testing

Given implications for treatment, natural history, and recurrence risk, provide or document genetic counseling (pre‑ and/or post‑test) when ordering testing, as implied by GeneReviews and ACMG references.

• Counseling is implied though not explicitly mandated in the policy; document that counseling was provided or offered in the medical record or prior auth submission.
• Consider referral to genetics specialists when available.

Order testing following evaluation by experienced providers

Order testing only after appropriate clinical evaluation by providers experienced in diagnosing connective tissue disorders; the policy expects professional judgment in selection of single‑gene versus panel testing.

• Document the evaluating provider's specialty or clinical rationale when relevant.
• Policy does not prescribe which specialties may order testing; providers are expected to use clinical judgment.

Policy does not replace clinical judgment — providers must use professional judgment

Providers are expected to exercise professional medical judgment; the policy is guidance and does not replace clinician judgment when deciding to order genetic testing.