Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes.

Fetal abnormalities are detected in 3% of all pregnancies and are responsible for approximately 20% of all perinatal deaths. Chromosomal microarray analysis (CMA) and exome sequencing (ES) are widely used in prenatal settings for molecular genetic diagnostics with variable diagnostic yields. In this study, we aimed to determine the diagnostic yield of trio-ES in detecting the cause of fetal abnormalities within a highly consanguineous population. In families with a history of congenital anomalies, a total of 119 fetuses with structural anomalies were recruited and DNA from invasive samples were used together with parental DNA samples for trio-ES and CMA. Data were analysed to determine possible underlying genetic disorders associated with observed fetal phenotypes. The cohort had a known consanguinity of 81%. Trio-ES led to diagnostic molecular genetic findings in 59 fetuses (with pathogenic/likely pathogenic variants) most with multisystem or renal abnormalities. CMA detected chromosomal abnormalities compatible with the fetal phenotype in another 7 cases. Monogenic ciliopathy disorders with an autosomal recessive inheritance were the predominant cause of multisystem fetal anomalies (24/59 cases, 40.7%) with loss of function variants representing the vast majority of molecular genetic abnormalities. Heterozygous de novo pathogenic variants were found in four fetuses. A total of 23 novel variants predicted to be associated with the phenotype were detected. Prenatal trio-ES and CMA detected likely causative molecular genetic defects in a total of 55% of families with fetal anomalies confirming the diagnostic utility of trio-ES and CMA as first-line genetic test in the prenatal diagnosis of multisystem fetal anomalies including ciliopathy syndromes.

Impact of Technology Use on Behavior and Sleep Scores in Preschool Children in Saudi Arabia.

Background: Pre-school children use digital devices both at home and in kindergarten for communication. However, such technologies can also be used for creativity learning and entertainment. Technology usage might exert a negative impact on the psychosocial development of pre-school children, thus necessitating parental monitoring. Previous studies have recommended early intervention for pre-school children by decreasing the duration of digital devices, spending more time with the family, and participation in motor activities to avoid the ill effects of technology. Aim: To investigate the impact of digital device use on the behavioral and sleep scores of preschool children as perceived by parents in Saudi Arabia (SA). Method: This cross-sectional study was conducted across two regions in SA. It was ethically approved by the ethical review board of Imam Abdulrahman Bin Faisal University. The participants were randomly selected from well-baby hospital records, surveyed and interviewed to obtain data for the following measures: demographic data, technology usage, sleep disturbance scale, and behavior scale. Children with special needs or comorbidities were excluded from the study. Descriptive and multivariate regression analysis were done. Results: We recruited 288 children. Most did not attend schools (63.2%), 22.6% were in kindergarten, and 14.2% were in nursery schools. Smart phones were the most commonly used device by the children (42.4%). Most used the technology for 2-3 h/days (34%). Cartoons were the most commonly sought content (42%). The behavior scores for children aged 18-36 months showed a mean value of 5.1, 3.7, and 4.6 for surgency, negative affect, and effortful control, respectively. Children aged 3-5 years showed a mean value of 4.3, 4, and 4.7 for surgency, negative affect, and effortful control, respectively. Sleep disturbance scores for all children showed a mean value of 12.4, 3.5, 3.8, 8, 7.3, and 2.7 on disorders of initiating and maintaining sleep, sleep-breathing disorders, disorders of arousal, sleep-wake transition disorders, disorders of excessive somnolence, and sleep hyperhidrosis, respectively. The mean total sleep score was 37. Multivariate regression analysis showed significant positive relationship between surgency and three factors namely family income of 10,000-15,000 SR (t = 1.924, p = 0.045), fathers' bachelor's degrees (t = 2.416, p = 0.16), and owning a video game device (t = 2.826, p = 0.005<0.05). Negative affect was significantly associated with fathers' diploma level of education (t = 2.042, p = 0.042). Negative significant relationship between effortful control and fathers' secondary level of education (t = -2.053, p = 0.041). There was a significant negative relationship between effortful control and owning a TV and video game device (t = -2.35, -2.855, p = 0.043, 0.005<0.05, respectively). A significant positive relationship was found between child's sleeping score (worse sleep) and watching technology between 3 and 5 h (t = 2.01, p = 0.045), and mothers' unemployment status (t = 2.468, p = 0.014). Conclusion: In conclusion, technology use is associated with a negative impact on children sleep and behavior. Owning a digital device, using tablets, screen viewing for more than 3-5 h, and watching movies were significantly associated with negative child's behavior and sleep.