CCDC39 Mutation-Related Primary Ciliary Dyskinesia with Congenitally Corrected Transposition of the Great Arteries: A...

BACKGROUND Primary ciliary dyskinesia (PCD) is an uncommon autosomal recessive disease resulting from dysfunction of motile cilia that causes impaired mucociliary clearance and abnormal embryonic left-right axis differentiation. The CCDC39 gene is a known cause of PCD, which is most commonly associated with inner dynein arm defects and microtubular disorganization. Although heterotaxy-related congenital heart defects are well described in PCD, their presence in patients with CCDC39 mutations, particularly those with congenitally corrected transposition of the great arteries (ccTGA), has not been previously described. CASE REPORT We report a female neonate was born to consanguineous Saudi parents with prenatal findings of dextrocardia, abdominal situs inversus, and ccTGA. Postnatal evaluation confirmed these findings, including a significant ventricular septal defect and moderate tricuspid regurgitation. She presented with early-onset respiratory symptoms of copious secretions and pneumonia requiring oxygen support and hospitalization. The whole-exome sequencing identified a novel homozygous frameshift variant in CCDC39 (c.2230_2233del p.Gln744Aspfs*17) and thus validated the diagnosis of PCD. Despite multidisciplinary management, the patient had cardiopulmonary arrest secondary to sepsis at 4 months of age. CONCLUSIONS This is the first report describing the relationship between CCDC39-related PCD and ccTGA, thereby expanding the phenotypic spectrum of CCDC39 mutations. This report emphasizes the pivotal role of motile cilia in cardiac morphogenesis and underscores the importance of considering PCD in neonates with laterality anomalies and complex congenital heart defects. Early genetic testing and a multidisciplinary approach are critical to timely diagnosis and management.