Genetic Testing (CFTR-mutations) for Cystic Fibrosis
Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
Cystic fibrosis is an inherited autosomal recessive disease of the exocrine glands associated with a high morbidity. It is characterized by impairment in the transport of chloride and sodium across cell membranes, which can result in an imbalance of water absorption, thereby causing dehydration. The liquid depletion results in the presence of thick and sticky mucus that causes blockage of ducts and tubes in various organs, including the lungs, pancreas, liver and intestines. Symptoms of cystic fibrosis may include chronic sinopulmonary diseases (e.g., chronic cough, bronchiectasis, pneumonia, and sinusitis), digestive complaints (e.g. foul-smelling greasy stools, intestinal blockage, meconium ileus, and failure to thrive, rectal prolapse), and reproductive difficulties (e.g., congenital absence of vas deferens, infertility).
Cystic fibrosis is caused by the presence of a variant on both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Variants in this gene result in impairment of the CFTR protein, which serves as a chloride channel allowing transport of chloride and sodium through the cell membrane. More than 1900 variants have been described in the CFTR gene; however, most of these variants are rare and their functional role has not been elucidated. Genetic testing for CFTR has a number of different applications, which include carrier testing and screening, testing of newborn after a positive screening, and identification of individuals who will benefit from specific drug therapies.
As an autosomal recessive disorder, both parents must carry some form of the CFTR gene mutation to have an affected child. Dual carrier parents have a 25% chance of having an affected child, a 25% chance of having an unaffected child, and a 50% chance of having a carrier child.
Genetic testing for CFTR mutations to determine the carrier status of an individual is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Genetic testing for the diagnosis of CFTR mutation related disorders (e.g. cystic fibrosis) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Pre- and post- genetic counseling as an adjunct to genetic testing is considered medically necessary.
Genetic testing for cystic fibrosis for use in mass screening and routine screening of newborns is considered not medically necessary.
Genetic testing for CFTR mutations using expanded carrier screening panels are considered investigational.
Genetic testing for CFTR mutations is considered medically appropriate if ALL of the following are met:
No previous genetic testing for CFTR mutation, or genetic testing was inconclusive
CFTR mutation analysis for ANY ONE of the following indications:
To determine carrier status in ANY ONE of the following:
Individual of reproductive age with a positive family history of cystic fibrosis
Parent or siblings of individuals in whom CFTR-gene mutations have been identified
Females who are pregnant, or considering pregnancy
Male reproductive partners of women identified as cystic fibrosis carriers
Reproductive partners of individuals with cystic fibrosis who are planning a pregnancy
Reproductive partners of individuals with congenital absence of vas deferens
Prenatal testing for CFTR gene mutation for ANY ONE of the following:
Either biological parent has a diagnosis of cystic fibrosis
Family history of cystic fibrosis in first degree relative (parent, child, brother, sister)
Both parents are carriers of CFTR mutations
Echogenic bowel has been identified on ultrasound in a fetus
Confirmation of a diagnosis of a CFTR gene mutation-related disorder for ANY ONE of the following:
Confirmation of a diagnosis of cystic fibrosis when ALL of the following are met:
Negative or intermediate range/equivocal sweat chloride test (i.e. range: 30-59mmol/L)
Clinical presentation consistent with cystic fibrosis such as ANY ONE of the following:
Idiopathic chronic (acute recurrent) pancreatitis present with inconclusive workup
Bronchiectasis with ALL of the following:
unexplained chronic or recurrent sinusitis
abnormal pulmonary function tests (PFTs)
Newborns too young to produce adequate volumes of sweat for sweat chloride test and ANY ONE of the following:
Congenital absence of vas deferens
Other symptoms indicative of Cystic Fibrosis
Newborn with an elevated level of immunoreactive trypsinogen (IRT) on dry blood spot screening
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
Laboratories that conduct genetic testing must comply with the provisions of the FDA’s Clinical Laboratory Improvement Act (CLIA).
American College of Medical Genetics and Genomics. (2008). Carrier screening in individuals of Ashkenazi Jewish descent. Retrieved August 30, 2017 from http://www.acmg.net/ACMG/Publications.
American College of Medical Genetics and Genomics. (2013). ACMG position statement on prenatal/preconception expanded carrier screening. Retrieved August 15, 2016 from http://www.acmg.net/ACMG/Publications.
American College of Obstetricians and Gynecologists. (2017, March). Carrier screening for genetic conditions. Committee Opinion #691. Retrieved August 11, 2017 from https://www.acog.org.
American College of Obstetricians and Gynecologists. (2017, March). Carrier screening in the age of genomic medicine. Committee Opinion #690. Retrieved September 20, 2018 from https://www.acog.org.
BlueCross BlueShield Association. Medical Policy Reference Manual. (4:2017). Carrier screening for genetic diseases (2.04.107). Retrieved August 7, 2018 from BlueWeb. (31 articles and/or guidelines reviewed)
eviCore® healthcare. (2019, January) Clinical guidelines; lab management program. Retrieved September 20, 2018 from www.evicore.com.
Ong, T., Marshall, S., Karczeski, B., Sternen, D, Cheng, E., & Cutting, G. (2001, March; last update February 2017). Cystic fibrosis and congenital absence of the vas deferens (Gene Reviews [Internet]), Seattle: Pagon, R.A., Adam, M.P., Ardinger, H.H., et al., editors.
ORIGINAL EFFECTIVE DATE: 6/1999
MOST RECENT REVIEW DATE: 1/31/2019
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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