Sickle Cell Disease Phenotypes and Obstructive Sleep Apnea; Are They Related?

OBJECTIVE: This study aims to compare the polysomnographic features between Arab-Indian and Benin phenotypes of sickle cell disease (SCD). MATERIALS AND METHODS: This prospective cross-sectional study was conducted in the Children's Hospital at King Fahad MedicalCity, in Riyadhwhere childrenwere recruited fromthe pediatric hematology clinic and pediatric sleepmedicine. All families were approached and patients who met the inclusion criteria and agreed to participate were included in the study. RESULTS: Eighty four children (37 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.65, 11) years and their body mass index z score was -1.45 (-2.195, -1.45). The evidence of obstructive sleep apnea (OSA) was more prominent in the Benin phenotype (66.7%) in comparison to those of the Arab-Indian (35.2%) phenotype ( p = 0.006). Additionally, 56.7% of Benin had moderate to severe OSA whereas Arab-Indian had 18% with a ( p = 0.0003). Controlling for other factors, the odds ratio (confidence interval) of having OSA in Benin phenotype was 4.68 (1.42-15.38) times higher as compared to Arab-Indian phenotype. CONCLUSION: The risk of having OSA as well as the severity of OSA is higher in Benin phenotype as compared to Arab-Indian phenotype which indicates the presence of potential OSA risk factors other than the SCD itself.

Clinical and molecular characteristics of primary ciliary dyskinesia: A tertiary care centre experience.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a ciliopathy with diverse clinical and genetic findings caused by abnormal motile cilia structure and function. In this study, we describe the clinical characteristics of confirmed PCD cases in our population and report the radiological, genetic, and laboratory findings. METHODS: This was a retrospective, observational, single-centre study. We enrolled 18 patients who were diagnosed with confirmed PCD between 2015 and 2019. We then analyzed their data, including clinical findings and workup. RESULTS: In our cohort, 56% of patients had molecularly confirmed PCD, and RSPH9 was the most common gene identified. Transmission electron microscopy (TEM) showed an ultrastructural defect in 64% of samples, all of which matched the genetic background of the patient. Situs inversus (SI) was observed in 50% of patients, and congenital heart disease was observed in 33%. The median body mass index (BMI) was 15.87 kg/m2, with a median z score of -1.48. The median FEV1 value was 67.6% (z score - 2.43). Radiologically, bronchiectasis was noted in 81% of patients at a variable degree of severity. Lung bases were involved in 91% of patients. We were unable to correlate the genotype-phenotype findings. CONCLUSION: We describe the clinical and molecular characteristics of patients with confirmed PCD in a tertiary centre in Saudi Arabia and report 9 new pathogenic or likely pathogenic variants in one of the PCD-associated genes.

An SFTPC gene mutation causes childhood interstitial lung disease: first report in the Arab region.

BACKGROUND: Surfactant protein C dysfunction is one of the causes of childhood interstitial lung disease but has not previously been reported in Arabian countries. CASE PRESENTATION: A six-year-old girl had presented at the age of eight months old with bronchiolitis followed by a persistent cough, dyspnea and hypoxaemia. She was found to have gastroesophageal reflux disease, but her symptoms did not resolve despite her therapy being optimised. Further tests, including a chest computed tomographic scan, lung biopsy and genetic testing, confirmed a diagnosis of surfactant protein C dysfunction. CONCLUSION: We report the first case in the Arab region of childhood interstitial lung disease caused by surfactant protein C deficiency.

Pediatric sickle cell disease and obstructive sleep apnea: A cross-sectional study in a tertiary pediatric center in Saudi Arabia.

OBJECTIVE: The aim of the study was to evaluate snoring and obstructive sleep apnea (OSA) in Saudi children with sickle cell disease (SCD). MATERIALS AND METHODS: This cross-sectional study was conducted among children with SCD attending a hematology clinic were recruited. Demographics, clinical data, and sleep questionnaires were collected and overnight polysomnographies performed. RESULTS: Seventy children (31 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.5, 11) years and their body mass index z-score was -1.2 (-2.0, -0.4). Seventy-four percent of SCD patients snored and 32 (46%) had evidence of OSA (obstructive apnea-hypopnea index [OAHI] ≥2 events per hour of sleep), 13 of whom had moderate OSA (OAHI ≥5 and <10 events per hour of sleep) and 10 had severe OSA (OAHI ≥10 events per hour of sleep). CONCLUSION: Snoring and the proportion of OSA were high in children with SCD. This underlines the importance of screening for OSA in all children with SCD.

Lung disease associated with filamin A gene mutation: a case report.

BACKGROUND: Mutations in the gene encoding filamin A (FLNA) lead to diseases with high phenotypic diversity including periventricular nodular heterotopia, skeletal dysplasia, otopalatodigital spectrum disorders, cardiovascular abnormalities, and coagulopathy. FLNA mutations were recently found to be associated with lung disease. In this study, we report a novel FLNA gene associated with significant lung disease and unique angiogenesis. CASE PRESENTATION: Here, we describe a 1-year-old Saudi female child with respiratory distress at birth. The child then had recurrent lower respiratory tract infections, bilateral lung emphysema with basal atelectasis, bronchospasm, pulmonary artery hypertension, and oxygen and mechanical ventilation dependency. Molecular testing showed a new pathogenic variant of one copy of c.3153dupC in exon 21 in the FLNA gene. CONCLUSIONS: Our data support previous reports in the literature that associate FLNA gene mutation and lung disease.