Background: Primary ciliary dyskinesia (PCD) due to CCNO mutations is frequently associated with more severe clinical phenotypes. This study reports our experience with three patients and reviews global characteristics of CCNO-related cases, providing insights for early diagnosis. Methods: We conducted a retrospective analysis of PCD patients with CCNO mutations and reviewed genotype-phenotype correlations in the literature. Results: Three pediatric cases of PCD with CCNO mutations were enrolled in our department. All patients were born with respiratory distress and exhibited recurrent wet cough, wheezing, or dyspnea. Bronchial mucosal biopsies from all patients revealed the absence of ciliary structures. Patients exhibited nasal nitric oxide (nNO) levels below the normal range. All three patients had sinusitis; Patient 1 also suffered from otitis media, mastoiditis and hearing loss. Head magnetic resonance imaging (MRI) revealed arachnoid cyst in patient 1 and ventricular enlargement in patient 3. Patient 2 carried a novel homozygous point mutation in exon 3 (c.884T>C/homo; p.L295P), and echocardiography revealed moderate pulmonary hypertension. Our literature review indicated that neonatal onset respiratory symptoms were the major manifestations. Low nNO levels were observed in 89.2% of patients. Heterotaxy was absent in all cases. Bronchiectasis was the most common radiological finding. A total of 20 mutations were identified in 55 patients. Conclusion: Neonatal respiratory distress and reduced nNO levels are common clinical features of CCNO-related PCD.Genetic testing is essential for the early diagnosis of CCNO-related PCD.