CFvantage® Cystic Fibrosis Expanded Screen

Diagnosis is based on evidence of an abnormality in cystic fibrosis transmembrane conductance regulator (CFTR) function and the presence of ≥1 characteristic phenotypic feature.¹ Such evidence may be based on 1 of the following:

• Presence of 2 disease-causing pathogenic variants (mutations) in the CFTR gene or
• 2 abnormal quantitative pilocarpine iontophoresis sweat chloride values (>60 mEq/L) or
• Transepithelial nasal potential difference (NPD) measurements characteristic of CF

Phenotypic features of CF include, but are not limited to, the following:

• Chronic sinopulmonary disease (chronic cough and sputum production, chronic wheeze and air trapping, obstructive lung disease on lung function tests, persistent colonization with pathogens commonly found in individuals with CF, chronic chest radiograph abnormalities, chronic pansinusitis, digital clubbing)
• Gastrointestinal/nutritional abnormalities (meconium ileus, rectal prolapse, malabsorption/pancreatic insufficiency, steatorrhea, hypoproteinemia, fat-soluble vitamin deficiencies, failure to thrive, distal intestinal obstructive syndrome, recurrent pancreatitis, biliary sludging, elevation of transaminases and gamma-glutamyl transferase, direct hyperbilirubinemia, chronic hepatobiliary disease)
• Obstructive azoospermia
• Salt-loss syndromes(acute salt depletion, chronic metabolic alkalosis, hyponatremic hypochloremic dehydration)

• Heterozygous means the individual carries 1 copy of a pathogenic variant (mutation) on 1 chromosome. If the mutation is associated with a recessive disease such as cystic fibrosis (CF), these individuals are called carriers. Carriers are typically unaffected; that is, they show no symptoms of the disease. 
• Homozygous means the individual carries 2 copies of the same pathogenic variant, 1 on each chromosome. If the mutation is associated with a recessive disease such as CF, these individuals are typically affected; that is, they show symptoms of the disease. However, the diagnosis is made based on clinical features and other laboratory studies.
• Compound heterozygous means the individual carries 1 copy each of 2 different pathogenic variants, 1 on each chromosome. If the mutations are associated with a recessive disease such as CF, these individuals are typically affected; that is, they show symptoms of the disease. However, the diagnosis is made based on clinical features and other laboratory studies.

It depends on the indication for the CF test.

For patients who are pregnant or planning pregnancy, guidelines recommend performing a CF screen on the reproductive partner.²

• If the partner is also a CF carrier, the couple has a 25% risk of having a child affected with CF. Guidelines recommend offering the couple genetic counseling and prenatal testing if both partners are CF carriers. 
• If the partner’s result is negative, the residual risk to be a CF carrier is reduced, and the risk for the couple to have a child affected with CF is also reduced. 

For patients suspected of having CF, additional genetic testing may be considered to determine whether a second rare pathogenic variant that may not be detected by the standard CF screen is present. Rare mutations in the CF gene may be detectable through full gene sequencing and/or gene deletion/duplication testing. Please call Quest Genomics Client Services at 866-436-3463 to discuss the case and additional testing options. 

Yes, the risk to offspring of this couple is 25%. CF is a recessive disease, so when offspring inherit any 2 disease-causing CF pathogenic variants, there is an increased risk to be affected with CF and CF-related conditions (eg, male infertility). It does not matter if the 2 CF pathogenic variants are the same or different; if a child inherits a CF pathogenic variant from each parent, the child does not inherit a normal, working gene. However, since some CF pathogenic variants may be less severe and cause milder symptoms, the exact symptoms of the child may be difficult to predict.

Providing patient ethnicity does not change the CF result. A positive result is still positive, and a negative result is still negative, regardless of ethnicity provided.

For negative results, the residual risk that a patient is a CF carrier is provided in a table in the report, which is broken down by ethnicity. So, one can look up the residual carrier risk by a patient’s specific ethnic group. The percent risk reduction is based on ethnicity, because the CF screen detection rate varies by ethnic group.

No, please call Quest Genomics Client Services at 866-GENE-INFO to discuss this case with a genetic counselor. Documentation of the specific CF mutations in the family will be necessary to accurately interpret the results of the testing that was performed on the patient. 

For patients with a clinical diagnosis of CF, additional genetic testing may be considered to determine whether rare pathogenic variants (mutations) that are not detected by this CF screen are present. Rare pathogenic variants in the CF gene may be detectable through full-gene sequencing and/or gene deletion/duplication testing.

Please call Quest Genomics Client Services at 866-436-3463 to discuss the case and additional testing options.