Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders Form

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

Revision log
Coding Implications

# CONCERT GENETIC TESTING: SKELETAL DYSPLASIA AND RARE BONE DISORDERS

See Important Reminder at the end of this policy for important regulatory and legal information.

## OVERVIEW

Skeletal dysplasias are a category of rare genetic disorders that affect bones and joints and are estimated to affect 2.4 per 10,000 births, and some forms of skeletal dysplasia can be suspected based on prenatal ultrasound. There are more than 350 distinct skeletal disorders that have been described, and some skeletal dysplasias can be lethal, often due to a significantly small rib cage that restricts lung development. The osteogenesis imperfecta group of disorders are sometimes classified as skeletal dysplasias, while other times they are considered bone fragility disorders.

Genetic testing has allowed for gene identification in more than two thirds of the skeletal dysplasias. Testing allows for more precise diagnosis facilitating health care providers’ care based on the established natural history of the individual disorder. For some skeletal dysplasias, knowing the specific disease causing variant or variants can impart prognostic information. A few skeletal dysplasias are currently amenable to pharmacologic therapy, though such therapies may be reserved for patients with confirmed genetic diagnosis. The familial recurrence risk and long term natural history differs based on the underlying genetic basis of disease.

Per GeneReviews*, osteogenesis imperfecta (OI) should be distinguished from child physical abuse/non-accidental trauma (NAT). The prevalence of physical abuse is much greater than the prevalence of OI, and on rare occasions, the two can be present concurrently. Patient history, family history, physical examination, radiographic imaging, fracture investigation, and the clinical course all contribute to distinguishing OI from NAT. The overlap in clinical features includes multiple or recurrent fractures, fractures that do not match the history of trauma, and the finding of fractures of varying ages and at different stages of healing. Rib fractures are much more common in NAT than in osteogenesis imperfecta.

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

*GeneReviews is an expert-authored review of current literature on a genetic disease, and goes through a rigorous editing and peer review process before being published online.

# POLICY REFERENCE TABLE

## Coding Implications

This clinical policy references Current Procedural Terminology (CPT®). CPT is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2023, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

The tests, associated laboratories, CPT codes, and ICD codes contained within this document serve only as examples to help users navigate claims and corresponding criteria; as such, they are not comprehensive and are not a guarantee of coverage or non-coverage. Please see the Concert Platform for a comprehensive list of registered tests.

| Criteria Sections | Example Tests (Labs) | Common CPT Codes | Common ICD Codes | Ref |
|-------------------|---------------------|-----------------|-----------------|-----|
| Osteogenesis Imperfecta | Osteogenesis imperfecta COL1A1 & COL1A2 NGS Panel (HNL Genomics) | 81406, 81408, 81479 | Q78.0, Z82.79 | 3 |
|                   | Osteogenesis Imperfecta Panel (PreventionGenetics, part of Exact Sciences) |                 |                 |     |
|                   | Osteogenesis Imperfecta NGS Panel - Dominant & Recessive (HNL Genomics) |                 |                 |     |
| Multigene Panel Analysis for Skeletal Dysplasia | Skeletal Disorders Panel (Invitae) | 81400, 81401, 81402, 81403, 81404, 81405, | M85, Q77, Q78 | 1, 7, 8 |

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

| or Rare Bone Disorder | Skeletal Dysplasia Core & Extended NGS Panel (HNL Genomics) | 81406, 81407, 81408, 81479 |                 |     |
|                      | Comprehensive Skeletal Dysplasias and Disorders Panel (Blueprint Genetics) |                 |                 |     |
|----------------------|--------------------------------------------------------|---------------------------|-----------------|-----|
| Other Covered Skeletal Dysplasias and Rare Bone Disorders | varies                                                | 81400, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408, 81479 | M85, Q77, Q78 | 2, 4, 5, 6 |

## OTHER RELATED POLICIES

This policy document provides criteria for Genetic Testing for Skeletal Dysplasia and Rare Bone Disorders. Please refer to:

- Genetic Testing: Aortopathies and Connective Tissue Disorders for criteria related to Ehlers-Danlos syndrome and other connective tissue disorders.
- Genetic Testing: Multisystem Inherited Disorders, Intellectual Disability, and Developmental Delay for criteria related to diagnostic testing for disorders that affect multiple systems.
- Genetic Testing: General Approach to Genetic and Molecular Testing for criteria related to skeletal dysplasias and rare bone disorders that is not specifically discussed in this or another non-general policy, including known familial variant testing.

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation





*Clinical features for a specific disorder may be outlined in resources such as GeneReviews, OMIM, National Library of Medicine, Genetics Home Reference, or other scholarly sources.

## DEFINITIONS

1. Non-accidental Trauma (NAT) refers to injury that is purposely inflicted upon a child (e.g., child abuse). NAT often occurs as injury to the skin and soft tissue, but approximately a third of NATs are fractures.

## BACKGROUND AND RATIONALE

### Osteogenesis Imperfecta

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation



## Other Covered Skeletal Dysplasia and Rare Bone Disorders

### International Skeletal Dysplasia Society

The International Skeletal Dysplasia Society published an updated categorization of skeletal dysplasias (Unger, 2023):

“The ‘Nosology of genetic skeletal disorders’ has undergo its 11th revision and now contains 771 entries associated with 552 genes reflecting advances in molecular delineation of new disorders thanks to advances in DNA sequencing technology....As with the previous versions, the list of disorders and genes in the Nosology may be useful in considering the differential diagnosis in the clinic, directing bioinformatic analysis of next-generation sequencing results, and provide a basis for novel advances in biology and medicine.” (p. 1165)

| Reviews, Revisions, and Approvals | Revision Date | Approval Date |
|----------------------------------|--------------|--------------|
| Policy developed.                | 03/23        | 03/23        |
| Semi-annual review. Updated title to reflect V1.2024 version. Overview, coding, reference-table, background and references updated. Throughout policy: replaced “coverage criteria” with “criteria”. For Policy Reference Table: added “81401, 81402, 81403, 81404, 81405, 81406, 81407”. For Other Related Policies: added “and Molecular”. For Criteria: under Multigene Panel Analysis for Skeletal Dysplasia or Rare Bone Disorder Panel: added “post-natal”; for Other Covered Skeletal Dysplasia and Rare Bone Disorders Panel: under I.O.1. removed “(also in Metabolic Policy)”; under II. added “and Molecular”. | 10/23        | 10/23        |
| Semi-annual review. Updated title to reflect V2.2024 version. In Overview and Clinical Considerations, policy overview updated to include information from the Clinical Considerations section, which has been consolidated into the Overview | 04/24        | 04/24        |

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders V1.2025 Date of Last Revision: 11/2024

Important Reminder

11

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders V1.2025 Date of Last Revision: 11/2024

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care and are solely responsible for the medical advice and treatment of member/enrollees. This clinical policy is not intended to recommend treatment for member/enrollees. Member/enrollees should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited.

12

Concert Genetic Testing: Skeletal Dysplasia and Rare Bone Disorders V1.2025 Date of Last Revision: 11/2024

Providers, member/enrollees, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, member/enrollees to member/enrollees and/or be bound by such terms and conditions by providing services to member/enrollees and/or submitting claims for payment for such services.

Note: For Medicaid member/enrollees, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

Note: For Medicare member/enrollees, to ensure consistency with the Medicare National Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs and LCDs and Medicare Coverage Articles should be reviewed prior to applying the criteria set forth in this clinical policy. Refer to the CMS website at http://www.cms.gov for additional information.

©2018 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene® and Centene Corporation® are registered trademarks exclusively owned by Centene Corporation.

back to top

13