CFTR-related disorders include cystic fibrosis (CF) and congenital absence of the vas deferens (CAVD). Cystic fibrosis affects epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, and exocrine sweat glands, resulting in complex multisystem disease. Pulmonary disease is the major cause of morbidity and mortality in CF. Affected individuals have lower airway inflammation and chronic endobronchial infection, progressing to end-stage lung disease characterized by extensive airway damage (bronchiectasis, cysts, and abscesses) and fibrosis of lung parenchyma. Meconium ileus occurs at birth in 15%-20% of newborns with CF. Pancreatic insufficiency with malabsorption occurs in the great majority of individuals with CF. More than 95% of males with CF are infertile as a result of azoospermia caused by absent, atrophic, or fibrotic Wolffian duct structures. CAVD occurs in men without pulmonary or gastrointestinal manifestations of CF. Affected men have azoospermia and are thus infertile.
Most commonly the diagnosis of cystic fibrosis (CF) is established in individuals with one or more characteristic phenotypic features of CF plus evidence of an abnormality in cystic fibrosis transmembrane conductance regulator (CFTR) function based on one of the following: presence of two disease-causing mutations in the CFTR gene or two abnormal quantitative pilocarpine iontophoresis sweat chloride values (>60 mEq/L) or transepithelial nasal potential difference (NPD) measurements characteristic of CF. The CFTR mutation detection rate varies by test method and ethnic background. In some symptomatic individuals, only one or neither disease-causing mutation is detectable; in some carriers, the disease-causing mutation is not detectable. The diagnosis of CFTR-related CAVD is established in males with azoospermia, low volume of ejaculated semen, absence of vas deferens on clinical or ultrasound examination, and at least one disease-causing mutation in CFTR.
CFTR-related disorders are inherited in an autosomal recessive manner. Sibs of a proband with cystic fibrosis and brothers of a proband with CAVD have a 25% chance of being affected, a 50% chance of being asymptomatic carriers, and a 25% chance of being unaffected and not carriers. Molecular genetic testing for disease-causing mutation(s) in the CFTR gene is used for carrier detection in population screening programs. Prenatal testing is available for pregnancies at increased risk for CFTR-related disorders if the disease-causing mutations in the family are known.