Pathophysiology

Cystic fibrosis is an autosomal recessive trait caused by mutations at a single gene locus on the long arm of chromosome 7. Cystic fibrosis reflects the loss of function of the CFTR protein. The CFTR protein normally regulates the transport of electrolytes and chloride across epithelial cell membranes.

More than 1,000 mutations of the CFTR gene have been described to date.Phenotypic appearance depends on the type of mutation (ie, class), location of the gene, molecular mechanism, and interaction with other mutations, as well as genetic and environmental influences.

The most common mutation of the CFTR gene is caused by the deletion of phenylalanine at position 508 (DF508, or delta-F508) and occurs with varying frequency in different ethnic groups. Worldwide, this allele is responsible for approximately 66% of all CF chromosomes.

Screening
Of the 1,000 or more infants born yearly with CF, most are diagnosed at a mean age of 3 to 4 years. Of note, nearly 10% of CF cases are diagnosed in individuals older that 18 years. Newborn screening for cystic fibrosis has been instituted in eight states, although national screening plans have not been mandated. In all, 10% of affected infants in the United States are diagnosed at birth either by prenatal diagnosis (3%) or by newborn screening (7%). The currently available genetic screening tools for CF include the Guthrie test, in which measurements of the immunoreactive trypsinogen in dried blood are taken, and measurement of the most common CF mutations, including DF508.

• Screening should be offered to (1) adults with a family history of CF, (2) reproductive partners of individuals with cystic fibrosis, (3) couples in whom one or both individuals are Caucasian (including Ashkenazi Jewish persons) and are planning pregnancy, and
• Screening should be made available to non-Caucasian or Ashkenazi-Jewish individuals or couples.

Issues to keep in mind include the gestational age at which the couple presents for prenatal care, and the feasibility of pregnancy termination. These factors should be included in the CF screening discussion with parents.