Genotype and pulmonary function in children with primary ciliary dyskinesia: a cross-sectional cohort study.

Children with molecularly confirmed PCD were diagnosed at a median age of 8.7 years, and most had parental consanguinity.

• The retrospective cross-sectional study included 44 children with biallelic pathogenic or likely pathogenic variants.
• Median age at diagnosis was 8.7 years (IQR 6-13).
• Parental consanguinity was present in 59.1% of patients.

DNAH5 was the most frequently identified gene in the cohort, followed by DNAH11 and CCNO.

• DNAH5 accounted for 22.7% of patients.
• DNAH11 and CCNO each accounted for 13.6%.
• Because gene-level subgroups were small, gene comparisons were labeled exploratory.

Spirometric parameters differed significantly across genotype-based groups, with the DNAH11 group showing the most preserved pulmonary function.

• FEV1% predicted, FEV1 Z-score, FVC Z-score, FEF25-75, FEF25-75% predicted, and FEV1/FVC differed across groups (all p < 0.05).
• The DNAH11 group had the most preserved pulmonary function profile.
• Comparisons were made across genotype-based groups.

In exploratory gene-level comparisons, CCNO and CCDC39/CCDC40 had numerically lower spirometric values, DNAH11 the most preserved, and DNAH5 an intermediate profile.

• Differences were described as numerical in the exploratory gene-level analyses.
• Subgroup sizes were small, so the findings are exploratory.

In adjusted regression, CCDC39/CCDC40 was associated with lower FEV1 z-scores and DNAH11 with higher FEV1 z-scores.

• CCDC39/CCDC40: B = -1.55, p = 0.002.
• DNAH11: B = 1.19, p = 0.023.
• The multivariable linear regression adjusted for age at diagnosis, BMI z-score, and bronchiectasis.
• These analyses were described as exploratory.

Neither DNAH5 nor CCNO was independently associated with FEV1 z-score in adjusted analyses.

• The model included DNAH5, DNAH11, and CCDC39/CCDC40 as described; the abstract reports no independent association for DNAH5 or CCNO.
• Adjustment covariates were age at diagnosis, BMI z-score, and bronchiectasis.

The genotype-phenotype pattern is consistent with previously reported findings from large cohorts, but needs confirmation in larger longitudinal studies.

• Prior large cohorts reported poorer lung function in CCNO and CCDC39/CCDC40 and relatively preserved function in DNAH11.
• This is described as one of the few exclusively pediatric cohorts linking genotype with spirometric phenotype using molecularly confirmed diagnoses.
• Authors call for larger longitudinal multicenter studies because of small subgroup sizes.