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

Cystic Fibrosis - Prenatal Diagnosis

Introduction and ContractingEdit

  • 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 HistoryEdit

Review Genes and ChromosomesEdit

  • 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 OverviewEdit

  • 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 CFEdit

  • 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


  • 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


  • 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


  • 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 mutationsEdit

  • 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 ScreeningEdit

  • 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 CarriersEdit

  • 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


  • 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 ConsiderationsEdit

  • 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


  • 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


The information in this outline was last updated in 2002.