What counseling is recommended for a pregnant individual who is a carrier of the cystic fibrosis transmembrane conductance regulator (CFTR) gene?

Counseling a Pregnant CFTR Carrier

Immediately test the partner for CFTR mutations and provide genetic counseling, as the couple has a 1 in 4 (25%) risk of having a child with cystic fibrosis if both are carriers. 1, 2

Immediate Actions

Partner testing is the critical next step. Once a pregnant woman is identified as a CFTR carrier, her partner must be offered carrier screening immediately using CFTR mutation analysis. 1, 2 This is time-sensitive given the pregnancy, as it determines reproductive risk and available options. 1

Genetic counseling must be provided to all CFTR carriers - this is a guideline requirement, not optional. 1, 2 The counseling should occur regardless of symptoms, family history, or pregnancy status. 1

Key Counseling Points

Carrier Status Explanation

• The pregnant woman carries one copy of a CFTR mutation and will not develop classic cystic fibrosis herself (assuming asymptomatic). 2
• Document the specific mutation identified (e.g., ΔF508, R117H, W1282X) as this impacts counseling. 2
• If R117H mutation is detected, reflex testing for 5T/7T/9T polythymidine tract variants is mandatory to determine clinical significance. 1, 2

Risk Assessment Based on Partner Testing

If partner tests positive (both carriers):

• 25% (1 in 4) risk with each pregnancy of having a child with cystic fibrosis 1, 2
• 50% (1 in 2) risk the child will be a carrier like the parents 2
• 25% (1 in 4) risk the child will inherit no mutations 2

If partner tests negative:

• Residual risk remains based on ethnicity and detection rate of the testing panel used: 1, 2
  • Ashkenazi Jewish: 1 in 930 residual risk (97% detection rate) 2
  • European Caucasian: 1 in 140 residual risk (80% detection rate) 2
  • African American: 1 in 207 residual risk (69% detection rate) 2
  • Hispanic American: 1 in 105 residual risk (57% detection rate) 2
  • Asian American: 1 in 90 baseline risk with limited detection data 2

Special Variant Considerations

For R117H carriers specifically:

• Mandatory reflex testing for 5T/7T/9T variants must be performed. 1, 2
• If R117H and 5T are in cis (same chromosome): Associated with variable CF phenotype when compound heterozygous with another CFTR mutation. 1, 2
• If R117H and 5T are in trans (opposite chromosomes): Relatively benign mutation associated with male infertility (CBAVD) but not classic CF; no known clinical features in females. 1, 2
• Parental testing is recommended to determine cis versus trans configuration. 1

Reproductive Options if Both Partners Are Carriers

Discuss all available options with the couple: 1, 2

• Prenatal diagnosis: Chorionic villus sampling (CVS) or amniocentesis to determine fetal genotype. 1, 3
• Preimplantation genetic testing (PGT-M): With IVF to select unaffected embryos for future pregnancies. 2
• Continuation of pregnancy: With preparation for potential CF diagnosis and management. 4
• Pregnancy termination: If prenatal diagnosis confirms affected fetus and couple chooses this option. 4
• Donor gametes: From non-carrier donors for future pregnancies. 2

Family Cascade Testing

Recommend carrier testing for at-risk family members: 1, 2

• Siblings of the carrier 2
• Parents if of reproductive age 2
• Extended family members of reproductive age 2
• The patient should be encouraged to inform relatives of their risk and availability of screening. 5

Common Pitfalls to Avoid

• Never assume a negative partner test eliminates all risk - residual carrier risk persists based on panel sensitivity and ethnicity. 1, 2
• Do not overlook R117H reflex testing - failure to test for 5T/7T/9T variants leads to incomplete counseling and missed clinical implications. 1, 2
• Avoid reassuring male R117H carriers about fertility without discussing CBAVD (congenital bilateral absence of vas deferens) risk. 1, 2
• Do not forget to modify residual risk calculations when family history of CF is present - the standard population-based calculations do not apply. 1, 2
• Never provide carrier screening results without offering genetic counseling - this violates guideline requirements. 1, 2, 5

Documentation Requirements

Document in the medical record: 2

• Specific CFTR mutation identified 2
• Patient's ethnicity for residual risk calculation 2
• Partner testing recommendation and results 2
• Genetic counseling provided 2
• Family cascade testing recommendations 2
• Reproductive options discussed if both partners are carriers 2

Timing Considerations

Couples identified during pregnancy face limited time for decision-making. 1 Most carrier couples who are pregnant at the time of screening choose prenatal diagnosis as the "next step," though this decision should be made after comprehensive genetic counseling. 4 Couples should be prepared that learning both are carriers can be emotionally overwhelming and unexpected. 4