# 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

* 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.