Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital

Abstract

Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20/37 (54.1%) had chronic rhinosinusitis, 28/37 (75.6%) had bronchiectasis, and 29/37 (78.4%) had recurrent pneumonia. A total of 17/37 (45.9%) individuals had transmission electron microscopy or genetic confirmation of PCD; 10 individuals had at least one positive pathogenic genetic variant in the PCD-related genes; however, only seven patients presented a conclusive result according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with two pathogenic variants in homozygous or compound heterozygous. The median age at diagnosis was 13 years, and the median time between suspicion and diagnosis was four years. Sixteen patients had class I electron microscopy alterations, seven had class II alterations, and 14 had normal transmission electron microscopy according to the international consensus guideline for reporting transmission electron microscopy results in the diagnosis of PCD (BEAT-PCD TEM Criteria). Genetic screening for pathogenic variants in PCD-related genes and transmission electron microscopy can help determine the PCD diagnosis; however, they are still unavailable to all individuals with clinical suspicion in Brazil. We described ultrastructural alterations found in our population along with the identification of pathogenic variants in PCD-related genes.

Keywords: Kartagener syndrome; bronchiectasis; ciliary motility disorders; genetic testing; microscopy; sinusitis; transmission electron microscopy.

Figure 1

Included patients’ algorithm and division by the degree of clinical suspicion. PCD: primary ciliary dyskinesia, TEM: transmission electron microscopy, N: number of individuals.

Figure 2

Transmission electron microscopy (TEM) findings as described in the “Better Experimental Approaches to Treat Primary Ciliary Dyskinesia” criteria (BEAT-PCD TEM criteria) from ERS [21] and TEM images of nasal brushing of patients from the study. (A) Normal ultrastructure (Case. 8). (B) TEM showing absence of inner and outer dynein arm combined with microtubular disorganization (Case 13). (C,D) Absent inner dynein and outer dynein arm and compound cilia (Case 15). (E) Two pairs of central microtubules (Case 29). (F) Absent inner dynein arm (Case 19). (G) Absent inner dynein arm (Case 21). (H) Absent inner dynein and outer dynein arm (Case 27). (I) Absence of inner dynein arm combined with microtubular disorganization and central complex defect (Case 28).