Motile cilia dysfunction causes Primary Ciliary Dyskinesia (PCD), situs inversus totalis, and a spectrum of laterality defects, yet the prevalence of laterality defects other than situs inversus totalis in PCD has not been prospectively studied.
In this prospective study, participants with suspected PCD were referred to our multi-site consortium. We measured nasal nitric oxide (nNO), examined cilia with electron microscopy (EM), and analyzed PCD-causing gene mutations. Situs was classified as (1) Situs Solitus (SS), (2) Situs Inversus Totalis (SI), or (3) Situs Ambiguus (SA), including heterotaxy. Participants with hallmark EM defects and/or biallelic gene mutations were labeled “classic PCD.”
Of 767 participants (median age 8.1 years, range 0.1-58), classic PCD was defined in 305, including 143 (46.9%), 125 (41.0%), and 37 (12.1%) with SS, SI, and SA, respectively. A spectrum of laterality defects was identified with classic PCD, including 2.6% and 2.3% with SA plus complex or simple cardiac defects, respectively, 4.6% with SA but no cardiac defect, and 2.6% with an isolated possible laterality defect. Participants with SA and classic PCD had higher prevalence of PCD-associated respiratory symptoms versus SA controls (year-round wet cough (p<0.001), year-round nasal congestion (p=0.015), neonatal respiratory distress (p=0.009), digital clubbing (p=0.021)) and lower nNO levels (median 12 nL/min vs 252 nL/min, p<0.001).
At least 12.1% of classic PCD have SA and laterality defects ranging from classic heterotaxy to subtle laterality defects. Specific clinical features of PCD and low nNO help identify PCD in patients with laterality defects.