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

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 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

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

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

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

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.