Handbook of Genetic Counseling/Cystic Fibrosis - Prenatal Diagnosis-1

Cystic Fibrosis - Prenatal Diagnosis

Introduction and Contracting

 * 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

Review Genes and Chromosomes
FACTS ABOUT CF
 * 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

CF Overview

 * 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
decreased fertility in females due to abnormal cervical mucus that can contribute to infertility
 * 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

Diagnosis

 * 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

 * 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

 * 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

 * 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
Results take about 2 weeks according to genzyme
 * 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

Options for Pregnancy and Future Pregnancies if Both Were Carriers

 * 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

 * 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

 * 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