Severe Single-Gene Disorders & Multi-System Deletions

Cystic Fibrosis (CF)

Autosomal Recessive Multi-System Exocrine Disorder

Primary risk age: Infancy through Adulthood (Screened at birth; symptoms develop in infancy)

Urgency: Severe
Typical age: Infancy through Adulthood (Screened at birth; symptoms develop in infancy)
Body system: Genetic & Chromosomal

Typical course: This is a lifelong genetic multi-system disorder requiring daily complex treatment.

Reviewed against AAP · CDC · WHO · NHS guidance Last reviewed 2026-06-13

1. Summary & Pathophysiology

Autosomal Recessive Multi-System Exocrine Disorder

Pathophysiology (Development Path)

The mutation disrupts the CFTR chloride channel, preventing chloride transport out of epithelial cells. This leads to increased sodium and water absorption, drying out mucosal surfaces and producing abnormally thick, sticky secretions in the lungs, pancreas, liver, and intestines, which blocks duct channels.

Primary Causes & Etiology

A mutation in the CFTR gene on chromosome 7, most commonly the delta-F508 mutation, which codes for the cystic fibrosis transmembrane conductance regulator protein.

2. Symptom Continuum

Early Onset Signs
Meconium ileus (bowel obstruction) in newborns within 48 hours of birth, or failure to thrive despite a robust appetite in early infancy.
Progressive Phase
Recurrent, wet cough, chronic wheezing, frequent bronchopneumonia (often infected with Pseudomonas aeruginosa), and pale, bulky, foul-smelling greasy stools (steatorrhea due to pancreatic insufficiency).
Severe Indicators
Progressive bronchiectasis, chronic respiratory failure, digital clubbing, nasal polyps, CF-related diabetes, biliary cirrhosis, and male infertility.

3. Clinical Verification

Newborn screening showing elevated immunoreactive trypsinogen (IRT). Confirmed by a Sweat Chloride Test showing chloride levels $ge 60 ext{ mEq/L}$ on two separate occasions.

4. Care & Elements Plan

Primary Care Treatment Plan

Aggressive pulmonary hygiene, including daily chest physiotherapy and nebulized bronchodilators/mucolytics. Administer oral pancreatic enzyme replacement capsules with every meal. Use CFTR modulator drugs if indicated by the genotype.

Home Support Elements

Perform chest percussion or use an airway clearance vest twice daily. Provide a high-calorie, high-fat diet with fat-soluble vitamin supplements (A, D, E, K). Maintain excellent hand hygiene.

Generic Active Ingredients (No Brands)

Pancrelipase (generic active pancreatic enzyme replacement capsules containing lipase, protease, and amylase)
Dornase alfa (nebulized recombinant DNase active ingredient to thin sputum)
Ivacaftor or Lumacaftor (CFTR modulator active ingredients targeting specific mutations).

Lists active elements only. Never administer self-designed therapies.

5. Doctor Critical Lines

Critical Thresholds: When to See a Doctor

Seek prompt care if a child with CF developments a fever, has increased cough, changes in sputum color, shortness of breath, or weight loss (pulmonary exacerbation).

6. Vaccine & Prevention

Routine Prophylaxis (Prevention)

Genetic carrier screening for parents; prenatal testing for known mutations.

Immunization Context

Up-to-date immunizations are critical, including annual influenza and pneumococcal vaccines, to protect the lungs.

7. Timelines & Outlook

Active Timeline

This is a lifelong genetic multi-system disorder requiring daily complex treatment.

Expected Prognosis

Progressive, life-shortening disorder. With modern aggressive therapy and CFTR modulators, median survival has increased to over 40-50 years.

Potential Untreated Complications

Chronic respiratory failure, bronchiectasis, pneumothorax, hemoptysis, distal intestinal obstruction syndrome, CF-related diabetes, and liver failure.

Moderate

Williams Syndrome

Autosomal Dominant Microdeletion Syndrome

Apparent in infancy and early childhood (Lifelong condition)

Severe

Prader-Willi Syndrome (PWS)

15q11-q13 Paternal Chromosomal Deletion Syndrome

Neonates through adulthood (recognized at birth due to hypotonia)