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ACOG/ACMG Recommendations CF Screening
- All women of reproductive age
- do not repeat if done earlier
- NBS results (from previous pregnancy) does not replace maternal carrier screening
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ACOG/ACMG Affected Women
- Affected women wants to become pregnant
- -multidisciplinary team: PF, Wt gain, infections, DM & PTD risk
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ACOG/ACMG Both parents carriers
refer to CG: review testing and reproductive options
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ACOG/ACMG Male with CF or isolated CBAVD
Refer to GC: mutation analysis & consult
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ACOG/ACMG Unaffected parents, + FH
Refer to GC & record review to ID mutations
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CF-Genetics
- AR genetic disorder
- Chrom 7
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CF Genetics
Mutation classes
- Class I-III most severe
- ---non functioning chloride channels
- Class IV-V milder forms
- --at least some functioning chloride channels
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CF-Genetics
- Most common single mutation
- DeltaF508 (65-70% of cases
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CF Genetic Panel (2 types)
Standard Panel (23) detects 75.3%
Pan ethnic battery (64) more $$ detects 81.4%
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CF-Who is at risk in the US
- All White: 1/2500 dis freq & 1/29 carrier (83%)
- Ashkenasi Jew: 1/2300 dis freq & 1/29 carrier (97%)
- Zuni & Pueblo Indian: 1/1580 & 1/3970 dis freq & 1/20 & 1/32 (? %) use Pan ethnic panel
- Hispanic: 1/9200 & 1/52 (56.9%)
- AA: 1/1500 & 1/61 (58%)
- Asian: 1/37,000 & 1/96 (37.5)
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CF-Patho
- Chloride ions pull water via osmotic gradient
- --no channel= dehydration or obstruction
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CF-Patho
Pulmonary: Dehydration
- Upper airway-chronic sinusitis
- Lower airway-thick, tenacious mucus, chronic cough, wheezing, frequent pneumonia and bronchitis
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CF-Patho
GI
- Proenzymes unable to exit pancreatic ducts
- early ongoing: fat malabsorption, poor weight gain, slowed linear growth
- late (2nd decade and beyond)
- gradual autodigestion of pancreas
- CF-rtelated diabetes mellitus (CFRD)
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CF-Reproduction: Obstruction
Male: CBAVD -may be only symptoms
- Female: Thick mucus
- ---impaired fall-decreased fallopian tube function-decreased fertility
- --degree of pulmonary disease highly correlated to pregnancy
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Diagnosis-NB Screening Carrier Testing
- Immune Reactive Trypsinogen (IRT)
- Serum analyte that "seeps" into bloodstream when ducts obstructed
- Results-vary depending on institution (cut offs 90%) or abnormal as top 4-5% other 10% of daily values
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CF-Options (Screening/Testing)
- Test pregnant woman and/or whoever has a the FH first
- NEG= carrier risk reduced NOT zero
- POS= testy partner-refer for GC
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CF-Both partner's positive
- 1:4 chance child has disease
- conduct:
- pregestational diagnostic testing
- prenatal diagnosis (amniocentesis, CVS)
- cord blood
- sweat chloride (>3 month of age)
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CF Testing Timing-A critical issue
Maternal
- Assume 10-14 days to obtain results
- Maternal testing 15 weeks
- Pos in 17 weeks
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CF Testing-Paternal
- Paternal counseling/testing- 18 weeks
- Positive results 20 weeks
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CF Genetic Counseling
20+ weeks
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CF Amonicentesis
- Test 21 weeks
- Results: 23 weeks
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Take home CF test
Ideally with new OB Labs
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CF-Diagnositc Testing
- Clinical Sx's, NBS result or parental genetic status typically prompt testing
- 1. DNA-based=genotype (amnio, cord, serum)
- 2. Sweat chloride=phenotype (<3 months may be false neg)
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CF-Genetic Counseling Critical Point
Reduces the chance that a patient is a carrier but cannot totally exclude it
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CF Carrier Risk
Both Parents carry CF mutation
Risk of offspring w mutation 1:4 or 25%
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CF Carrier Risk
One Parent has CF and one is carrier
- All offspring have at least 1 mutation
- -risk for having an offspring carrier 2:4 or 50%
- -risk for having an affected offspring 2:4 or 50%
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CF Carrier Risk
One parent is a carrier, partner status unknown
- --known carrier (1:1 risk of carrier status)
- --assume partner at high risk (1:29 risk)
- math: 1:1x1:29=1:29x1:1:4=1:116 risk affected offspring
- JUSTIFIES Amnio risk
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CF Carrier Risk
One parent has SIBLING with CF, parent status unknown
What is the parents risk of being a carrier
- --they are not affected
- --their risk of being a carrier 2:3 or 66%
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CF Carrier Risk
One parent has a NEICE/NEPHEW with CF
Don't know their status
What is risk of being carrier
Their risk of being carrier 2:4 or 50%
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CF Risk what all patients should know
- What a recessive condition is?
- What is CF?
- Who is at risk?
- Who is at lower risk?
- What testing options are available?
- Limitations of CF testing
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