Demographic, phenotypic and genotypic characteristics of patients diagnosed with primery ciliary dyskinesia with situs inversus totalis

Demographic, phenotypic and genotypic characteristics of patients diagnosed with Primary Ciliary Dyskinesia with Situs Inversus Totalis. Objective: Primary ciliary dyskinesia is an autosomal recessive disease. The estimated prevalence of PCD is approximately one in 20000 live births. It progresses with chronic upper and lower respiratory tract infections starting from the infantile period due to ciliary dysfunction. It is characterized by decreased ciliary movement (immotile cilia) or deterioration (ciliary dyskinesia). During the embryonic period, asymmetry occurs because the nodal cilia controlling the normal position of the heart and internal organs is defective. Therefore, approximately 50% of patients with primary ciliary dyskinesia have situs inversus totalis. The diagnosis of the disease is based on clinical, radiological, genetic features, video and electron microscopy examinations. Demographic, phenotypic and genotypic characteristics of patients with situs inversus totalis and primary ciliary dyskinesia were investigated. Material and Methods: The demographic, phenotypic and genotypic characteristics of 48 patients with Situs Inversus Totalis and a diagnosis of Primary Ciliary Dyskinesia between the ages of 1-22 who were followed up from Bezmialem Vakif University Pediatric Pulmonology outpatient clinic, were investigated through thorax CT performed in the last 2 years, abdominal USG and echocardiography performed at any period, nasopharyngeal aspirate or sputum culture results, personal history, family history information, drugs used or used for a long time, Respiratory Function Tests performed in the last year, body mass index, genetic test results, radiological findings and examination information made by a pediatric pulmonologist. The data were analyzed in the SPSS program. 14 Results: There were no significant difference between patients with and without genetic mutation in gender, BMI, Bhalla score, PİCADAR score, North American score, family history of asthma, skin findings (atopy, eczema, itching, dryness, etc.), snoring, GER, neonatal respiratory distress, NİCU history, history of hospitalization, consanguineous marriage history, chronic rhinitis, chronic sinusitis, bronchiectasis, chronic otitis and hearing loss, congenital heart anomalies, ENT examination, bronchoscopy history, microbiology, drug use and PFT rates (p>0.05). There were no significant difference between patients with and without DNAH5 mutation in gender, BMI, Bhalla score, North American score, family history of asthma, skin findings (atopy, eczema, itching, dryness, etc.), snoring, GER, history of hospitalization, consanguineous marriage history, chronic rhinitis, chronic sinusitis, bronchiectasis, chronic otitis and hearing loss, congenital heart anomalies, ENT examination, bronchoscopy history, microbiology, drug use and PFT rates(p>0.05). İn the group with DNAH5 mutation neonatal respiratory distress, NİCU history and PİCADAR score rates were significantly (p<0.05) lower than in the group without DNAH5 mutation. Consanguineous marriage was seen in 43 (90%) patients. It was determined that the 47(%98) patients had term births, and 36(%75) of them had neonatal respiratory distress. It was determined that 30(%63) patients had been nicu hospitalisation and 29(60%) of them had at least 2 times lower respiratory tract infections in the following periods. In 5 (10%) of the patients cardiac problems were observed. A history of snoring was obtained from 18 (37%) of the patients. Diagnostic and therapeutic bronchoscopy was performed on 26 (56%) patients. 29 operations were performed on 20 (42%) of patients for 7 different reasons. In 22 (46%) of the patients chronic rhinitis was observed. Chronic sinusitis was detected in 37(77%) patients. Otitis and hearing loss was detected in 31 (65%) patients. Gastroesophageal reflux was detected in 10 (21%) of the patients. Bronchiectasis was seen in 31 (65%) patients. Skin symptoms such as eczema, atopy, pruritus findings detected in 5 (10%) patients. 24 (50%) of the patients were thin according to their body mass index (BMI), 20 (42%) patients were normal and 4 (8%) patients were overweight. 31 patients had PFT. FEV1 values were >80 in 10 (32%) patients, 60-79 in 14 (45%) patients, 40-59 in 6 (20%) patients, and <40 in 1 (3%) patient. FVC value >80 in 10 patients, 13 (42%) patients 60-79, 40-59 in 7 (23%) patients and <40 in 1 (3%) patient. In 42 (87%) patients, 86 growths were 15 seen as 13 different pathogens. İn 30 (35%) patients H. influenzae, in 19 (22%) S. pneumoniae in 10 (%12)patients, M. Catarrhalis, in 10 (12%) patients, P. Aeruginosa in 6 (7%) patients, S. Aureus in 3 (4%) patients, S. Marcescens in 2 (2%) patients, S. Pyogenes and 6 more pathogens, respectively, A. Baumannii, E. Coli, S. Maltophilia, K. Oxytoca, C. Freundii, E. Cloacae detected. Diagnostic PICADAR scoring was applied to the patients included in the study. This score was above 10 points in 34 (71%), 7-9 points in 11 (23%) and 6 points in 3 (6%) patients. According to another North American scoring, 24 (50%) patients received maximum 4 points, 21 (44%) 3 points and 3 (6%) patients 2 points. Modified Bhalla scoring based on CT results of 31 patients taken in the last 2 years done. This score was mild in 12 patients, moderate in 18 patients, and severe in 1 patient. 36 (75%) of the patients were treated with inhaled steroid, 2 (4%) theophylline, 26 (54%) 2 agonists, 20 (42%) nasal steroids, 7 (15%) herbal medicines and it was learned that 31 (65%) of the patientswere used azithromycin for 6 months. Whole exome sequencing genetic analysis was performed on 40 (83%) of the 48 patients included in the study. No mutation was found in 8 of the patients. Since the results of 5 patients were suspicious, and they were directed to medical genetics for reinvestigation and they genetical data were not used in the study. The most common mutation was DNAH5 and it was seen in 8 (25%) patients. Additional mutations that may cause other diseases were detected in 9 patients. Three of them were considered significant. In one of the patients with DNAH5 mutation, a HFE gene mutation was detected, that can cause Hereditary Hemochromatosis. A mutation in the PAH gene, which may cause Phenylketonuria, was found in the patient with another DNAI2 gene mutation. In a patient with CCDC103 mutation, detected mutation in CFTR gene that may cause Cystic Fibrosis. Genetic analysis could not be performed for different reasons in 4 of 37 patients with chronic sinusitis, and mutation in 5 patients not detected. Chronic sinusitis was observed in all patients carrying the DNAH5(8), DNAi2(2), CCDC151(2), ARMC4(1), CCDC39(3) and CCDC40(2) mutation. Chronic sinusitis was detected in 75% of patients with CCDC103(3) mutation. Since the genetic results were suspicious in 4 patients, they were required for genetic analysis again. Bronchiectasis was detected in 31 (65%) patients. Most common mutation in these patients was DNAH5(7(23%)). İn 7(%23) patients for different reasons genetic analysis could not be performed. No mutation was detected in 4 16 (13%) of the patients. CCDC103 mutation was detected in 3 (10%) patients. Bronchiectasis was seen in all our patients with mutations CCDC151(2(6.5%)) and DNAI2(2(6.5%)). In patients with rhinitis the most common mutation was DNAH5. No mutation was detected in 3 of the patients. İn 3 patients for different reasons genetic analysis could not be performed. CCDC103 mutation was detected in 3 patients. Rhinitis is present in both of our patients with DNAI2 mutations. Conclusion: It was observed that there was no significant difference in demographic, phenotypic, clinical, and radiological findings of patients with PSD and SİTdiagnosed with positive and negative genetic results. When patients with DNAH5 mutations were compared with patients with other mutations, it was seen that newborns had fewer respiratory distress complaints, had fewer NICU admissions, and had lower PICADAR scores. İn the genetic results obtained, it was seen that there was no significant difference compared to the results in other literature and studies. Key words: situs inversus totalis; primary ciliary dyskinesia; child; bronchiectasis; chronic cough