Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis
Background: Primary ciliary dyskinesia (PCD; MIM 242650) is a rare genetic disorder characterized by malfunction of the motile cilia resulting in reduced mucociliary clearance of the airways. Together with recurring infections of the lower respiratory tract, chronic rhinosinusitis (CRS) is a hallmar...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-10-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1258374/full |
| _version_ | 1797667811572580352 |
|---|---|
| author | Andre Schramm Johanna Raidt Anika Gross Maik Böhmer Achim Georg Beule Heymut Omran |
| author_facet | Andre Schramm Johanna Raidt Anika Gross Maik Böhmer Achim Georg Beule Heymut Omran |
| author_sort | Andre Schramm |
| collection | DOAJ |
| description | Background: Primary ciliary dyskinesia (PCD; MIM 242650) is a rare genetic disorder characterized by malfunction of the motile cilia resulting in reduced mucociliary clearance of the airways. Together with recurring infections of the lower respiratory tract, chronic rhinosinusitis (CRS) is a hallmark symptom of PCD. Data on genotype–phenotype correlations in the upper airways are scarce.Materials and methods: We investigated the prevalence, radiologic severity, and impact on health-related quality of life (HrQoL) of CRS in 58 individuals with genetically confirmed PCD. Subgroup analysis was performed according to the predicted ultrastructural phenotype based on genetic findings.Results: Among 58 individuals harboring pathogenic variants in 22 distinct genes associated with PCD, all were diagnosed with CRS, and 47% underwent sinus surgery. A total of 36 individuals answered a German-adapted version of the 20-item Sinonasal Outcome Test (SNOT-20-GAV) with a mean score of 35.8 ± 17, indicating a remarkably reduced HrQoL. Paranasal sinus imaging of 36 individuals showed moderate-to-severe opacification with an elevated Lund–Mackay Score (LMS) of 10.2 ± 4.4. Bilateral agenesis of frontal sinus (19%) and sphenoid sinus (9.5%) was a frequent finding in individuals aged 16 years or older. Subgroup analysis for predicted ultrastructural phenotypes did not identify differences in HrQoL, extent of sinus opacification, or frequency of aplastic paranasal sinuses.Conclusion: PCD is strongly associated with CRS. The high burden of disease is indicated by decreased HrQoL. Therefore, the upper airways of PCD individuals should be evaluated and managed by ear–nose–throat (ENT) specialists. Genetically determined PCD groups with predicted abnormal versus (near) normal ultrastructure did not differ in disease severity. Further studies are needed to gain evidence-based knowledge of the phenotype and management of upper airway manifestations in PCD. In addition, individuals with agenesis of the frontal and sphenoid paranasal sinuses and chronic respiratory symptoms should be considered for a diagnostic evaluation of PCD. |
| first_indexed | 2024-03-11T20:19:56Z |
| format | Article |
| id | doaj.art-f3f02a465c4341dabe4d6251a9bd602d |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-11T20:19:56Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-f3f02a465c4341dabe4d6251a9bd602d2023-10-03T08:57:51ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-10-011010.3389/fmolb.2023.12583741258374Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitisAndre Schramm0Johanna Raidt1Anika Gross2Maik Böhmer3Achim Georg Beule4Heymut Omran5Department of General Pediatrics, University Hospital Muenster, Muenster, GermanyDepartment of General Pediatrics, University Hospital Muenster, Muenster, GermanyDepartment of General Pediatrics, University Hospital Muenster, Muenster, GermanyClinic for Radiology, University Hospital Muenster, Muenster, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Muenster, Muenster, GermanyDepartment of General Pediatrics, University Hospital Muenster, Muenster, GermanyBackground: Primary ciliary dyskinesia (PCD; MIM 242650) is a rare genetic disorder characterized by malfunction of the motile cilia resulting in reduced mucociliary clearance of the airways. Together with recurring infections of the lower respiratory tract, chronic rhinosinusitis (CRS) is a hallmark symptom of PCD. Data on genotype–phenotype correlations in the upper airways are scarce.Materials and methods: We investigated the prevalence, radiologic severity, and impact on health-related quality of life (HrQoL) of CRS in 58 individuals with genetically confirmed PCD. Subgroup analysis was performed according to the predicted ultrastructural phenotype based on genetic findings.Results: Among 58 individuals harboring pathogenic variants in 22 distinct genes associated with PCD, all were diagnosed with CRS, and 47% underwent sinus surgery. A total of 36 individuals answered a German-adapted version of the 20-item Sinonasal Outcome Test (SNOT-20-GAV) with a mean score of 35.8 ± 17, indicating a remarkably reduced HrQoL. Paranasal sinus imaging of 36 individuals showed moderate-to-severe opacification with an elevated Lund–Mackay Score (LMS) of 10.2 ± 4.4. Bilateral agenesis of frontal sinus (19%) and sphenoid sinus (9.5%) was a frequent finding in individuals aged 16 years or older. Subgroup analysis for predicted ultrastructural phenotypes did not identify differences in HrQoL, extent of sinus opacification, or frequency of aplastic paranasal sinuses.Conclusion: PCD is strongly associated with CRS. The high burden of disease is indicated by decreased HrQoL. Therefore, the upper airways of PCD individuals should be evaluated and managed by ear–nose–throat (ENT) specialists. Genetically determined PCD groups with predicted abnormal versus (near) normal ultrastructure did not differ in disease severity. Further studies are needed to gain evidence-based knowledge of the phenotype and management of upper airway manifestations in PCD. In addition, individuals with agenesis of the frontal and sphenoid paranasal sinuses and chronic respiratory symptoms should be considered for a diagnostic evaluation of PCD.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1258374/fullciliopathyPCDgenotype phenotype correlationsinusitishealth related quality of life |
| spellingShingle | Andre Schramm Johanna Raidt Anika Gross Maik Böhmer Achim Georg Beule Heymut Omran Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis Frontiers in Molecular Biosciences ciliopathy PCD genotype phenotype correlation sinusitis health related quality of life |
| title | Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis |
| title_full | Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis |
| title_fullStr | Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis |
| title_full_unstemmed | Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis |
| title_short | Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis |
| title_sort | molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis |
| topic | ciliopathy PCD genotype phenotype correlation sinusitis health related quality of life |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1258374/full |
| work_keys_str_mv | AT andreschramm moleculardefectsinprimaryciliarydyskinesiaareassociatedwithagenesisofthefrontalandsphenoidparanasalsinusesandchronicrhinosinusitis AT johannaraidt moleculardefectsinprimaryciliarydyskinesiaareassociatedwithagenesisofthefrontalandsphenoidparanasalsinusesandchronicrhinosinusitis AT anikagross moleculardefectsinprimaryciliarydyskinesiaareassociatedwithagenesisofthefrontalandsphenoidparanasalsinusesandchronicrhinosinusitis AT maikbohmer moleculardefectsinprimaryciliarydyskinesiaareassociatedwithagenesisofthefrontalandsphenoidparanasalsinusesandchronicrhinosinusitis AT achimgeorgbeule moleculardefectsinprimaryciliarydyskinesiaareassociatedwithagenesisofthefrontalandsphenoidparanasalsinusesandchronicrhinosinusitis AT heymutomran moleculardefectsinprimaryciliarydyskinesiaareassociatedwithagenesisofthefrontalandsphenoidparanasalsinusesandchronicrhinosinusitis |