Chronic Cough, Dyspnea, and a Novel CCDC39 Variant: A Case Report of Heterotaxy Syndrome Without Cardiac Anomalies and Associated Primary Ciliary Dyskinesia

Heterotaxy syndrome is characterized by abnormal left-right arrangement of thoracoabdominal organs and is frequently associated with complex cardiac anomalies. However, cases with predominant extracardiac manifestations are increasingly recognized. This report describes a 20-year-old female of North African descent with consanguineous parentage, who presented with chronic cough and exertional dyspnea persisting over several years. Clinical examination, biochemical analyses, and vital signs were unremarkable, and there was no reported history of environmental exposures or tuberculosis. Pulmonary function testing revealed severe airway obstruction, reversible with bronchodilators. Imaging studies demonstrated a diffuse bronchiolitis pattern, an enlarged azygos vein, and polysplenia. Abdominal CT (computed tomography) revealed an interrupted inferior vena cava with azygos continuation, an enlarged left liver, a multinodular spleen, and distal pancreatic atrophy. Methicillin-resistant <i>Staphylococcus aureus</i> was identified in bronchoalveolar lavage, and the patient was treated with intravenous vancomycin. Further evaluations, including sinus CT, revealed bilateral frontal sinus aplasia, hypoplasia of other sinuses, and structural abnormalities such as the absence of uncinate processes. Nasal biopsy showed absent ciliary motility, and transmission electron microscopy revealed inner dynein arm defects and central apparatus abnormalities without outer dynein arm involvement. Genetic testing identified a novel homozygous c.2347_2351del (p.Phe783ThrfsTer3) PVS1 null variant in exon 17 of the <i>CCDC39</i> gene, associated with autosomal recessive primary ciliary dyskinesia-14. This case highlights the overlap between heterotaxy syndrome and primary ciliary dyskinesia, suggesting that the ciliary defect contributed to both the patient's organ laterality defects and chronic respiratory symptoms. The findings underscore the importance of a comprehensive evaluation of structural and functional abnormalities and the role of genetic testing in managing atypical presentations of heterotaxy syndrome.