Chronic rhinosinusitis in mom and daughter marked by CF symptoms
Neither had known CFTR gene mutations, but signs of problems with protein
A woman and her daughter were diagnosed with chronic rhinosinusitis, an inflammatory condition of the sinuses and nasal passages, with features matching cystic fibrosis (CF), a case study reports.
However, neither patient carried mutations in the CFTR gene that cause CF.
The pair also presented with signs and symptoms matching two other conditions: primary immunodeficiencies and primary ciliary dyskinesia.
“This case is unique as features of all 3 disorders coexist in a mother-daughter pair,” the scientists wrote.
The case study, “Short Cilia, Immunodeficiency, and Cystic Fibrosis in a Mother-Daughter Pair,” was published in the Ear, Nose & Throat Journal.
Hard-to-treat rhinosinusitis can be due to underlying diseases like CF
Symptoms of chronic rhinosinusitis, or CRS, include nasal congestion, discharge, and a poor sense of smell lasting at least three months. Treatment typically includes antibiotics, immune suppressive corticosteroids, and possible surgery if medical therapy is ineffective.
Potential underlying causes for refractory (hard-to-treat) CRS include CF, a disease caused by inherited mutations in the CFTR gene that result in no or faulty CFTR protein. This deficiency leads to the production of abnormally thick and sticky mucus in various organs, including the airways and lungs.
Other factors that can cause CRS include primary ciliary dyskinesia (PCD), a genetic disease that affects the tiny, hairlike structures (cilia) that line the airways, and primary immunodeficiencies (PID), a group of conditions in which the immune system does not function correctly.
Researchers in Canada described the case of a mother and daughter with refractory CRS presenting with features consistent with CF, PCD, and PID.
The woman, age 58, and her daughter, age 20, presented with chronic nasal blockage associated with fluid or pus discharge, postnasal drip (excessive mucus), loss of sense of smell, and facial pain. Frequent antibiotic courses failed to relieve these symptoms, which then were managed with saline rinses and steroid nasal sprays. Both tested negative for allergies.
Visual examination using endoscopy confirmed fluid discharge, as well as small polyps, or abnormal tissue growth, but only in the mother. CT scans showed signs of inflammation, narrowing of the nasal passages, and smaller-than-normal sinuses. Chest X-rays, CT scans, and lung function tests were all normal.
Based on these findings, the mother was diagnosed with CRS with nasal polyps, and the daughter had CRS without nasal polyps. However, prescribed daily rinses with a corticosteroid (budesonide) failed to improve their condition.
A few years later, both women underwent endoscopic sinus surgery, which involved using a thin, flexible tube with a camera to visualize and remove blockages in the sinuses. While their CRS symptoms eased for the short term, they returned.
CF, primary ciliary dyskinesia, and primary immunodeficiencies in evidence
Scientists evaluated both patients for CF as a potential cause of CRS. Indeed, sweat chloride levels, the gold standard test to diagnose CF, were consistently above the normal value of less than 40 millimolar per liter (mmol/L): 61 mmol/L in the mother and 53 mmol/L in the daughter.
However, both patients tested negative for CFTR gene mutations. Years later, the mother also developed borderline pancreatic insufficiency, a common CF digestive symptom.
Findings suggested “CFTR dysfunction despite the absence of identifiable disease-causing mutations,” the scientists wrote.
When the mother was assessed for PID, her blood levels of certain antibodies — IgA, IgG, and IgG — were low or below the normal range, and remained suppressed one year later. Antibody levels in response to a pneumococcal vaccine also were below the normal range. Together, these results suggested common variable immunodeficiency, the team noted.
After the daughter consented to a mucus membrane biopsy, microscopy images revealed fewer cilia per cell and shorter than normal cilia, both signs of PCD. Genetic testing then uncovered a mutation in her DNAH11 gene, which has been implicated in causing PCD.
“Refractory CRS may be multifactorial, with features of multiple diseases simultaneously contributing,” the scientists wrote. “Patients with refractory CRS should be further evaluated to identify alternative diagnoses and ensure proper management.”
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