The packet lists CFTR, on chromosome 7, as the single known gene, with autosomal recessive inheritance. No ClinGen validity classification beyond the gene symbol is supplied. GeneReviews describes the CFTR chloride channel as needed for ion transport out of the respiratory epithelium.

GeneReviews states that parents of an affected individual are presumed to be heterozygous for a CFTR pathogenic variant, and that when both parents are known heterozygotes each sibling has, at conception, a 25% chance of being affected, a 50% chance of being heterozygous and a 25% chance of inheriting neither variant. It lists increased risk of conditions such as bronchiectasis, asthma and recurrent pancreatitis among heterozygotes. On genotype and phenotype, GeneReviews reports the strongest correlation for pancreatic function, with pancreatic sufficient alleles dominant for that phenotype, while pulmonary severity varies widely among individuals with identical genotypes.

The packet lists newborn screening by immunoreactive trypsinogen (IRT), the sweat chloride test described as the gold standard confirmatory test, and CFTR genetic testing. Cystic fibrosis is a CORE condition on the Recommended Uniform Screening Panel: HHS recommends the condition for inclusion in state newborn-screening panels; actual state panels vary. GeneReviews states that CF newborn screening has been universal in the United States since 2010, uses IRT with follow-up molecular testing that varies by state, and that elevated results require diagnostic sweat chloride testing.

GeneReviews states that the diagnosis is established in a proband with a positive newborn screen, suggestive signs or symptoms, or a first-degree relative with CF, together with a sweat chloride value of 60 mmol/L or higher, biallelic CFTR pathogenic or likely pathogenic variants, or a nasal potential difference measurement consistent with CF. An intermediate sweat chloride of 30-59 mmol/L is described as prompting evaluation with a CF specialist. Its differential diagnosis table includes primary ciliary dyskinesia, X-linked agammaglobulinemia, common variable immunodeficiency and Shwachman-Diamond syndrome.

GeneReviews states that there is no cure for CF and that CFTR modulator targeted therapy is available to mitigate manifestations. The packet's foundational therapies are airway clearance techniques, pancreatic enzyme replacement therapy with meals and snacks, nutritional supplementation including fat-soluble vitamins, inhaled mucolytics (dornase alfa), inhaled hypertonic saline, and inhaled antibiotics for chronic Pseudomonas colonization.

The packet's approved-treatment records with market status ACTIVE, the FDA-approved options documented here, are Alyftrek (vanzacaftor, tezacaftor and deutivacaftor; 2024), Trikafta (elexacaftor, tezacaftor and ivacaftor; 2023), Bronchitol (mannitol; 2020), Orkambi (lumacaftor and ivacaftor; 2018), Symdeko (tezacaftor and ivacaftor; 2018), Kalydeco (ivacaftor; 2015), inhaled tobramycin products (TOBI and related; 1997 to 2014), Cayston (aztreonam; 2010) and Pulmozyme (dornase alfa; 1993). GeneReviews ties modulator indications to age and CFTR variant type. Orphan designations for amphotericin B and alpha1-proteinase inhibitor (human) appear in the packet; designation is not approval.

GeneReviews describes supportive care as multidisciplinary, including care at a CF specialist center, antibiotics for chronic suppression and pulmonary exacerbations, eradication attempts for Pseudomonas aeruginosa, enzyme and vitamin supplementation for pancreatic insufficiency, and management of meconium ileus and salt loss. Lung transplantation is mentioned as a treatment option in severe lung disease.

The packet supplies no certified survival or life expectancy estimate. GeneReviews identifies lung disease as the major cause of morbidity and mortality, states that progression to severe lung disease occurs in many people with CF, and describes bacterial infections and pulmonary exacerbations as contributing to lung function decline. Pulmonary severity is described as varying widely among individuals with identical genotypes. More than 50% of people with CF in the United States are reported as older than 18 years.

The packet reports 219 CF records on ClinicalTrials.gov, all counted as active. Detailed records include NCT07283770, a Phase 1 evaluation of VX-581 in healthy participants and participants with cystic fibrosis, sponsored by Vertex Pharmaceuticals Incorporated (recruiting; start 2025-12-09). NCT07892443 examines type 2 inflammation in adults with CF, sponsored by the University of Virginia (not yet recruiting; start 2026-11-01). NCT07889973, sponsored by Istituto Giannina Gaslini, assesses protein function loss and potential CFTR function restoration (recruiting; start 2024-09-01). NCT07568119, sponsored by Cognita Labs LLC, assesses an airway clearance device (active, not recruiting; start 2024-02-17). Phase information is not supplied for most records.

Research directions in the packet include CFTR modulators for additional rare mutations, gene therapy and gene editing, mRNA therapy, anti-inflammatory strategies and microbiome-based interventions. GeneReviews describes read-through agents and gene therapy, including CRISPR and antisense approaches, for the approximately 10% of individuals not eligible for current therapy because of nonsense or rare variants.