Disease Profile: Cystic Fibrosis
For more about
the gene that causes cystic fibrosis, see the CFTR
Gene Profile. The following was taken from NIH
Publication No. 95-3650.
Ages - In medieval folklore, infants
with salty skin, a symptom of cystic fibrosis, are considered "bewitched"
because they routinely die an early death.
- Fanconi refers to the previously nameless condition as "cystic
fibrosis with bronchiectasis."
- Andersen of Columbia University develops the first comprehensive
description of cystic fibrosis symptoms.
- Lowe establishes that cystic fibrosis is a recessive genetic disorder.
- After observing excessive dehydration of cystic fibrosis patients
during a New York City heat wave, di Sant' Agnese of Columbia University
formally reports to the American Pediatric Society that CF patients
secrete excessive amounts of salt in their sweat. This observation
leads to development of the sweat test as a diagnostic standard
for cystic fibrosis.
1980's - Researchers associate organ damage caused by CF with
a malfunction of the epithelial tissue.
- Team led by Tsui and Riordan of the Hospital for Sick Children
in Toronto discover the gene responsible for CF and name its protein
product cystic fibrosis transmembrane conductance regulator (CFTR).
The gene is mapped to chromosome 7q.
1. Online Mendelian Inheritance in Man, OMIM (TM). Johns
Hopkins University, Baltimore, MD. MIM No.: 602421 (September 10,
2001) . <http://www.ncbi.nlm.nih.gov/omim/>
P.M. Quinton. "Physiological Basis of Cystic Fibrosis: A Historical
Perspective." Physiological Reviews 79 (1 Suppl.):
M.J. Welsh and A. E. Smith. "Cystic Fibrosis." Scientific
American 273 (6): 52-59.
fibrosis (CF) is a chronic, progressive, and frequently fatal genetic
(inherited) disease of the body's mucus glands. CF primarily affects the
respiratory and digestive systems in children and young adults. Sweat
glands and the reproductive system also are usually involved. On average,
individuals with CF have a lifespan of about 30 years.
CF is an autosomal
caused by mutations in the CFTR (cystic fibrosis transmembrane conductance
regulator) gene. Heterozygous carriers (those who have inherited only
one copy of the altered gene) are asymptomatic. Two altered genes must
be present for CF to appear. This means that if both parents are CF carriers,
their offspring would only express CF symptoms if they had inherited one
defective copy of the CFTR gene from each parent.
According to data collected by the Cystic Fibrosis Foundation,
about 30,000 Americans, 3000 Canadians, and 20,000 Europeans have CF.
The disease occurs mostly in whites whose ancestors came from northern
Europe, although it affects all races and ethnic groups. Accordingly,
it is less common in African Americans, Native Americans, and Asian Americans.
About 2500 babies are born with CF each year in the United States. Also,
about 1 in every 20 Americans is an unaffected carrier of an abnormal
CF gene. These 12 million people usually are unaware that they are carriers.
CF does not follow the same pattern in all patients but affects different
people in different ways and to varying degrees. The basic problem, however,
is the same—an abnormality in the glands that produce or secrete sweat
and mucus. Sweat cools the body; mucus lubricates the respiratory, digestive,
and reproductive systems and prevents tissues from drying out, protecting
them from infection.
Loss of excessive
amounts of salt in sweat can upset the balance of minerals in the
blood, which may cause abnormal heart rhythms. Shock also is a risk.
Thick accumulations of mucus in the intestines and lungs result in
malnutrition, poor growth, frequent respiratory infections, breathing
difficulties, and eventually permanent lung damage. Lung disease is the
cause of death in most patients.
Various other medical problems may include inflammation of the nasal
sinuses, nasal polyps, clubbing of fingers and toes, pneumothorax (rupture
of lung tissue and trapping of air between the lung and chest wall), coughing
of blood, heart enlargement, abdominal pain and discomfort, gassiness,
and rectal prolapse. Liver disease, diabetes, pancreatic inflammation,
and gallstones also occur in some people with CF.
Diagnosis and Genetic Testing
is the most common test for CF. It measures the amount of salt (sodium
chloride) in the sweat.
Immunoreactive Trypsinogen Test (IRT) is used for newborns who
do not produce enough sweat for the sweat test. In the IRT test, blood
drawn 2 to 3 days after birth is analyzed for a specific protein called
trypsinogen. Positive IRT tests must be confirmed by sweat and other tests.
tests that can assist in the diagnosis of CF include chest X rays,
lung function tests, sputum (phlegm) cultures, and stool examinations
to help identify typical digestive abnormalities.
Molecular Genetic Testing involves carrier screening and direct
DNA analysis. Current tests, however, cannot detect all of the more than
900 gene mutations, and so the tests are only 80% to 85% accurate .
CF once was always fatal in childhood. Better treatment
methods developed over the past 20 years have increased the average lifespan
of CF patients. At present, neither gene therapy nor any other kind of
treatment exists for the basic causes of CF, although several drug-based
approaches are being investigated. In the meantime, doctors can only ease
the symptoms of CF or slow the progress of the disease so the patient's
quality of life is improved. This is achieved by antibiotic therapy combined
with treatments to clear the thick mucus from the lungs. The therapy is
tailored to the needs of each patient. For patients whose disease is very
advanced, lung transplantation may be an option.
Jonathan F., et al. (Updated 12 April 2001). Cystic Fibrosis. In: GeneReviews
at GeneTests·GeneClinics: Medical Genetics Information Resource [database
online]. Copyright, University of Washington, Seattle. 1997-2001. Available
or http://www.genetests.org. Accessed
20 May 2002.
and Support Groups
Fibrosis Research, Inc.
Cystic Fibrosis Foundation
Fibrosis World Wide
Cystic Fibrosis Information and Support
Fibrosis Testing - From GeneCare Medical
Fibrosis Carrier Testing: A Guide for Parents - Publication created
by the Michigan State University DNA Diagnostic Program
NOAH About: Cystic Fibrosis - Links to CF resources by New
York Online Access to Health (NOAH)
Fibrosis Studies - Listed
Trials Information - From the Cystic Fibrosis Foundation
Cystic Fibrosis Clinical Trials Registry - From the Cystic Fibrosis
Other Cystic Fibrosis Resources
Entry for Cystic Fibrosis
Genes and Disease Entry for Cystic Fibrosis
Hopkins Medicine: Cystic Fibrosis
Fibrosis - From the National Institute of Diabetes and Digestive and Kidney Disorders
Last updated: November 27, 2002