Abstract / Summary
Background/Objectives: Primary ciliary dyskinesia (PCD) caused by biallelic RSPH4A variants is enriched in the Puerto Rican population due to the founder allele c.921+3_921+6delAAGT, a 4-nucleotide deletion affecting the intron 6 splice donor. This study aimed to characterize the genotype–computed tomography (CT) phenotype associated with homozygosity for this founder variant and examine relationships among age, pulmonary function, and structural lung disease. Methods: We performed a cross-sectional analysis of 20 genetically confirmed patients homozygous for RSPH4A c.921+3_921+6delAAGT. Demographic characteristics, spirometry, and chest CT findings were evaluated. Structural disease burden was quantified using a Bhalla-style CT severity score, and regression analyses assessed associations among age, CT severity, sex, and forced expiratory volume in 1 s (FEV1). Results: Mean FEV1 was 48.9% predicted (range, 26–65%) and showed no measurable association with age (slope −0.02% per year; 95% CI, −0.26 to +0.22; p = 0.88). Bronchiectasis was multilobar, with right-middle-lobe involvement in 80% of patients. CT severity showed a modest cross-sectional increase with age, whereas FEV1 remained relatively stable across age groups. In multivariable analysis, greater CT severity showed the strongest association with lower FEV1 (β = −0.56% per CT point; 95% CI, −1.13 to +0.01; p = 0.07), although this association did not reach statistical significance. Conclusions: In this Puerto Rican RSPH4A founder cohort, substantial airflow obstruction was observed across the age spectrum, while structural CT abnormalities were greater in older patients despite relatively stable FEV1. This cross-sectional dissociation suggests that spirometry alone may incompletely reflect structural disease burden. These findings support the complementary role of CT imaging in phenotypic characterization and longitudinal assessment of RSPH4A-related PCD and provide a rationale for earlier identification and future longitudinal studies.