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 Obtain Medical and Family History Review Genes and Chromosomes 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 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 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 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 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 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 References 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 The information in this outline was last updated in 2002.