Cystic Fibrosis
Cystic fibrosis (CF) is a chronic genetic disease that primarily affects the lungs
and digestive system. It is the result of a defective gene that is inherited from
one or both parents. Cystic fibrosis is characterized by thick mucus and
secretions that can block airways and disrupt the function of the digestive
system. Individuals with CF typically have a shortened life expectancy of 20-40
years, although patients with less severe forms of the disease may live
considerably longer. Although the disease has no cure, advances in the
treatment of symptoms associated with CF have improved the quality of life of
patients.
Symptoms of Cystic Fibrosis
The common symptoms of cystic fibrosis include:
 Salty tasting skin
 Malnourishment and inability to gain weight
 Frequent respiratory infections
 Coughing and shortness of breath
Cystic Fibrosis in Children
Cystic fibrosis often becomes apparent during childhood and as early as
infancy.
Parents should speak to their pediatrician if a child exhibits any of these
symptoms:
 Lack of proper growth; malnutrition, low weight
 Persistent cough that produces mucus
 Repeated lung or sinus infections
 Frequent fatty, bad-smelling stools
 Trouble passing first stool; constipation and meconium ileus in infants
 Rectal prolapse
If a child has difficulty breathing, medical care should be sought immediately.
What causes the symptoms of Cystic Fibrosis?
Cystic fibrosis is a complex disorder, involving multiple organ systems. Pathology
stems from the inability of cells and tissues to properly regulate transport of
chloride ions across epithelial membranes. This process is critical to the
production of sweat, mucus and digestive fluids. The inability to properly
regulate chloride and sodium transport results in the thickening of mucus fluids in
affected organs, such as the lungs, pancreas, intestine, liver, and the
reproductive system.
Lungs and Upper Respiratory System: A mucus layer normally coats and
protects the inner surface of the lungs and sinuses. In CF patients, thickening of
the mucus in these tissues causes congestion and difficulty in breathing. Mucus
builds up in the lungs blocks airways and prevents clearance. The mucus can
trap bacteria and other microbes that cause disease leading to frequent
pulmonary and sinus infections. Increased inflammation in the lungs and
airways leads to lung damage. Breathing difficulties and chronic lung infections
are major complications associated with the disease, and are the leading
cause of mortality in CF patients.
Gastrointestinal Tract and Digestion: The cells of the pancreas produce
digestive enzymes that aid in the breakdown and digestion of food. In
individuals with cystic fibrosis these secretions are much thicker than normal and
block the pancreatic and hepatic ducts. This prevents the access of digestive
enzymes to the intestinal tract resulting in constipation, decreased nutrient
absorption and subsequent malnutrition, and weight loss. Obstruction of the
hepatic ducts also leads to liver damage and cirrhosis. Obstruction of the
pancreatic ducts leads the destruction of Langerhans cells, which produce
insulin, and subsequent development of CF-related diabetes.
Infertility: Cystic fibrosis affects fertility in both men and women. Most men with
CF (approximately 97%) have congenital bilateral absence of the vas deferens
(CBAVD). Male patients with CBAVD are able to produce sperm but the ducts
that transport sperm have not developed and, thus, the individual is sterile. In
women with CF, thickening of cervical mucus or malnutrition (leading to
absence of menstruation or the disruption of ovulation) may cause infertility.
Genetics of Cystic Fibrosis
Cystic fibrosis is an autosomal recessive genetic disorder caused by defects
(mutations) in the CFTR gene. An individual with CF has inherited a defective
CFTR gene from each parent. The CFTR gene encodes a protein (Cystic Fibrosis
Transmembrane Conductance Regulator) that forms a channel through cell
membranes that helps move chloride ions in and out of cells. A defective CFTR
protein can cause fluids and secretions (sweat, mucous, digestive juices)
produced by cells to become unusually thick and viscous. Several mutations
have been identified in the CFTR gene. The features and severity of the disease
vary according to the specific mutations and their effect on the CFTR protein.
Each person has two copies of the CFTR gene, one copy inherited from each
parent. An individual with two normal copies (no mutations) does not have CF.
The CFTR mutation is “recessive”. If an individual has one normal and one
defective copy of the CFTR gene, he or she shows no symptoms of CF, but is
considered a “carrier” of CF.
Only those individuals who possess two copies of the mutated CFTR gene exhibit
symptoms associated with CF.
For example, parents who are both carriers of a defective CFTR gene have a 1
in 4 chance (25%) of having children with CF.
These parents have a 50% chance of having children who are carriers of a
defective CFTR gene, but who are unaffected by the disease.
Similarly, carrier parents also have a 25% chance of having children who have
two normal copies of CFTR gene and are hence not carriers and are unaffected
by CF.
Epidemiology
Cystic fibrosis is the most widespread life-limiting autosomal recessive disorder.
The incidence of CF varies according to ethnicity (Table 1). Cystic fibrosis is most
prevalent in Caucasians of European descent; approximately 4% are carriers of
a mutated CFTR gene. Cystic fibrosis is very rare in people of Asian and Middle
Eastern descent; just over 1% of Asians are carriers for a mutated CFTR gene.
Table 1
Ethnic Group
Ashkenazi Jewish
Caucasian
Hispanic American
African American
Asian American
Incidence
Carrier
Frequency
1:2270
1:2500
1:13,500
1:15,000
1:35,100
1:24
1:25
1:58
1:61
1:94
[Palomaki et al 2004]
Who should be tested for CF?
Testing for the presence of CFTR mutations is indicated for individuals in the
following circumstances:
 Presence of symptoms of cystic fibrosis
 Family history of CF (i.e. parents, siblings)
 Individuals whose parent tested positive as a carrier for a defective CFTR
gene
 Those who have a family history of CF, and are considering family
planning options.
Genetic Testing for Cystic Fibrosis:
There are many mutations that can occur in the CFTR gene that can result in CF.
The severity of the disease can vary according to the nature of the defect in the
CFTR gene. Genetic tests can detect the most common CFTR mutations that
cause CF. A physician can obtain a small blood sample that contains patient
DNA, which can be tested for the presence of CFTR mutations.
Treatment of Cystic Fibrosis
Cystic fibrosis is an incurable disease. However, the quality of life and life
expectancy of CF patients has improved considerably largely due to treatment
regimens aimed at diminishing the symptoms of CF:
Improved nutrition under medical supervision
Dietary supplementation with fat-soluble vitamins
Improvement of digestion and absorption with pancreatic enzyme
supplements
High-calorie diet
Clearance of lungs and airways
Medicinal intervention to maintain open airways
(bronchodilators, inhaled steroids, mucolytic agents)
Chest percussion to break up mucus
Control of respiratory infections
Antibiotics
References and Resources
Palomaki GE, Fitzsimmons SC, Haddow JE 2004. Clinical sensitivity of prenatal
screening for cystic fibrosis via CFTR carrier testing in a United States panethnic
population. Genet Med 6(5):405-414.
CFTR-Related Disorders, GeneReviews™ [Internet].
Pagon RA, Bird TD, Dolan CR, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-.
NCI Bookshelf. A service of the National Library of Medicine, National Institutes of
Health.
CF Living: website Helpful information and support for CF patients and their
families regarding diet and nutrition, treatments, and coping with cystic fibrosis.
Website includes many resources for children, teens, young adults, and adults.
Cystic Fibrosis Foundation (www.cff.org)
Cystic Fibrosis Foundation – Genetic Carrier Testing Updated 07/09/07
Center for Disease Control (CDC): Cystic Fibrosis Fact Sheet
American Lung Association: Cystic Fibrosis
Mont Sinai Hospital Health Library: Cystic Fibrosis