Handbook of Genetic Counseling/Cystic Fibrosis - Prenatal Diagnosis-1
Cystic Fibrosis - Prenatal Diagnosis
Introduction and Contracting
edit- What are your main reasons for seeking genetic counseling?
- Do you have any particular questions or concerns you would like to discuss?
- Address any immediate concerns or indicate that they will be addressed later during the discussion
- Outline the session including the information they want to know
- First I'll obtain more information about medical and family history to determine if there is anything else that we may want to discuss today
- Then we can discuss cystic fibrosis and answer any questions you have
Obtain Medical and Family History
editReview Genes and Chromosomes
edit- Sometimes it is helpful to review some basic genetics principles because it is not something most people think about every day.
- Review genes and chromosomes and explain autosomal recessive inheritance
FACTS ABOUT CF
CF Overview
edit- CF is one of the most common inherited diseases (affects 1 in 3300 live births in US)
- occurs in individuals of all races and ethnicities, but is most common in Caucasians
- Due to changes in both copies of a gene that instructs the body about how to make a protein channel that transports sodium and chloride into cells that line certain organs
- These channels are either not made or don't work properly
- This leads to production of thick mucus in the lungs which then leads to an increased risk of infections and pneumonia that may require periods of hospitalization
- It can also cause interference with digestion, which can lead to diarrhea and poor growth
- It also often causes infertility in males and may cause decreased fertility in females
Features of CF
edit- normal intelligence
- features may include
- chronic sino-pulmonary disease: cough, sputum production, wheezing, obstructive lung disease, chronic chest radiograph abnormalities, digital clubbing
- gastrointestinal/ nutritional abnormalities: malabsorption/ pancreatic insufficiency (foul, bulky, fatty stools) distal intestinal obstructive syndrome, rectal prolapse, recurrent pancreatitis, chronic hepatobiliary disease, failure to thrive, hypoproteinemia, fat soluble vitamin deficiencies
- infertility: 98% of males with CF infertile due to unilateral or bilateral agenesis of vas deferens
decreased fertility in females due to abnormal cervical mucus that can contribute to infertility
Diagnosis
edit- median age diagnosed is 6-8 months (2/3 dx before age 1)
- diagnoses established in people with one or more phenotypic features and one of following
- presence of 2 disease-causing mutations in the CFTR (cystic fibrosis transmembrane regulator) gene
- two abnormal quantitative sweat chloride values (the "gold standard")
- painless, relatively inexpensive, definitive answer)
- abnormal value for the transepithelial nasal potential difference (NPD)
- diagnosis established in absence of phenotypic characteristics when
- confirmed dx of sibling and abnormal sweat chloride value or presence of same two mutations as in the sibling
Prognosis
edit- survival increased from 18 years 1976 to 30.1 years 1995 currently approximated at 33 yrs (geneclinics)
- pulmonary disease major cause morbidity and mortality
- patients with pancreatic sufficiency (<10%) have milder course and greater survival (56 yrs 1995 CFF Patient Registry
- wide variability in disease expression
Incidence
edit- Caucasians 1/2,500
- African-Americans 1/18,000
- Asian Americans 1/90,000
- 30,000 affected in US 8,000,000 carriers in US
- carrier rates see chart in visual aids
CF gene and common mutations
edit- located on 7q
- 250,000 bp, 27 exons and 1,480 aa's
- functions as a regulated chloride channel in epithelial cells
- over 900 known mutations (most point mut. or small del.)
- genotype/phenotype correlation (both severe and mild mutations)
- delta F508 most common (30-80% of mutations)
CF Carrier Screening
edit- As mentioned CF occurs more frequently in Caucasians than other ethnicities (one in 25,000 Caucasians affected and 1 in 28 are carriers)
- AR inheritance, both parents must be carriers to have child with CF
- a blood test is offered that can determine if an individual is a carrier of CF
- assess whether interested in this testing
- testing at CHMC now offered and screens for 25 of most common mutations
- now CHMC does the panel for ________????
- GENZYME panel of 87
- carrier detection rate with the panel is 90% if of Northern European Descent and 70% if of Southern European descent.
- The 87 mutation analysis by genzyme detects 85-90% of carriers if Caucasian
- cost was $265 when done through CHMC, but sent to genzyme CHMC added on a lab fee
Results take about 2 weeks according to genzyme
Options for Pregnancy and Future Pregnancies if Both Were Carriers
edit- Testing can determine if a fetus is affected before they are born
- Amnio can be performed to test and see if fetus has CF and it is greater than 99% accurate if the mutations that parents carry are known
- Future pregnancies also have option of CVS performed earlier than amnio 10-12 weeks
- Describe if interested
- preimplantation genetic diagnosis-Where they perform genetic testing on embryos obtained using in vitro fertilization techniques. Then only implant those that don't have CVS
- If interested would be important to review costs and success rates
Review
edit- Assess if there are any questions or other concerns throughout the session
- Assess how they feel about carrier testing
- Offer patient literature on CF
Psychosocial Considerations
edit- May be nervous about pregnancy due to earlier loss
- Normalize early losses
- May not know much about partner's history
- Check to determine who she has for support family friends
- Assess their experience with CF and make certain to explain that the symptoms and how affected someone is varies even among family members with same mutation
- May think risk is higher than it is for CF so get a feel for how likely she thinks it is
References
edit- www.geneclinics.org
- Bianchi, D.W., Crombleholme T.M., D'alton, M.E. Fetology: Diagnosis & Management of the Fetal Patient. McGraw Hill, New York, 2000
- Kuller, J.A., Chescher, N.C., Cefalo, R.C. Prenatal Diagnosis and Reproductive Genetics. Mosby Year Book Inc. 1996.
- http://www.reproductivegenetics.com/preimplantation.shtml
- www.geneclinics.com
Notes
editThe information in this outline was last updated in 2002.