Abstract Background Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal recessive disorder characterized by motile cilia dysfunction. The diagnosis is often delayed, even in children who have characteristic clinical features of PCD, in part related to limitations of available diagnostic tests (1). According to diagnostic guidelines from the American Thoracic Society, a positive result on an extended genetic panel is considered diagnostic of PCD (2). Pathogenic variants in CCDC40 gene account for approximately 9% of PCD cases while DNAH8 mutation is less common, both usually follow a recessive type of inheritance (3). We present a case of PCD diagnosed by confirmed ciliary biopsy, in the setting of PCD genetic panel test revealing two heterozygous variants of unknown significance in the CCDC40 and DNAH8 genes. Case An 18-year-old male presents to our clinic for evaluation and further management of severe persistent asthma. He previously required multiple PICU admissions for asthma-exacerbations being refractory to treatment with one previous intubation due to COVID-19 pneumonia. Past medical history is also significant for chronic sinusitis with recurrent eosinophilic polyposis and allergic fungal sinusitis s/p multiple FESS. Previous work-up imaging with chest CT SCAN demonstrated evidence of bronchiectasis and CFTR full gene sequencing completed with no genes identified. His course was complicated by Pseudomonas aeruginosa infection, adequately treated and eradicated. Upon new visit to our clinic, he reported worsening of symptoms and repeated spirometry showed severely decreased parameters when compared to previous with physical exam remarkable for diffuse rhonchi, expiratory wheezing, poor air entry bilaterally, at that point he was transferred to the inpatient service, a repeated CT SCAN showed signs consistent with necrotizing pneumonia with progression of bilateral lower lobe bronchiectasis and mediastinal lymphadenopathy, sputum positive for Pseudomonas aeruginosa and RVP for influenza. A bronchoscopy was performed, and biopsy of the cilia was obtained; the specimen demonstrated multiple cilia with absent dynein arms, predominantly involving the internal arm and cilia with abnormal structure consistent with a diagnosis of PCD. Discussion Variants of uncertain significance or those not yet reported as disease causing may be identified in patients whose clinical phenotype is strongly suggestive of the disease, we present two heterozygous mutations usually associated with a recessive type of inheritance, raising the question of whether PCD may have an association with a digenic inheritance pattern. This case underscores the persistent limitations in achieving a definitive diagnosis, especially due to overlap with other much more common etiologies. This abstract is funded by: None
Rodriguez et al. (Fri,) studied this question.