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Exome sequencing (ES) has been utilized in diagnosing children with neurodevelopmental manifestations, this study aimed to investigate the utility of ES in children within a highly consanguineous population that presented with neurodevelopmental complaints. A retrospective chart review was performed for 405 children with neurodevelopmental complaints who have had ES and were evaluated in multiple centers in the United Arab Emirates over a four‐year period. Within the cohort of 405 children, consanguinity was reported in 35% (144/405). The primary clinical presentations were developmental delay/cognitive impairment, distinctive facial features, hypotonia, seizures, and weakness. The diagnostic yield was 57% (231/405). Novel variants were identified in 54% (125/231) of positive cases. Within the positive cases, specific treatment was available in 6% (13/231) and copy number variants (CNV) were reported in 3% (8/231) of cases. In eight children, variants in genes that have not yet been linked to human disease that could potentially be the cause of the observed phenotype "candidate genes" were identified. ES was utilized effectively within this cohort with a high diagnostic yield and through the identification of novel gene variants, CNVs, candidate genes and secondary findings as well as the alteration of the treatment plan in cases where treatment was available. [ABSTRACT FROM AUTHOR]

Background: Sleep is a vital physiological function for the maintenance of health and quality of life by ensuring body rest and restoring its energy levels. Remarkably, some children have sleep disordered breathing (SDB) that can disturb their normal sleep and affect the quality of their lives., Objective: The aim of this study was to assess the correlation between SDB and growth impairments and wether the growth parameters vary among genders., Methods: This study was conducted in two steps: 1500 questionnaires were distributed to children aged 3 to 12 years. The questionnaire covered personal information, medical history, and the Pediatric Sleep Questionnaire. The latter was used to evaluate the incidence of sleep-disordered breathing and was completed by parents of the involved children. Growth assessment was then determined for the population to find the correlation between sleep disorders and growth impairments., Results: A total of 931 completed questionnaires were returned (70.7% response rate). Among the respondents, 56.3% were females whereas 43.3% were males. The mean age was 8 years. The result showed that 16.11% of children were at high risk of sleep-disordered breathing. A significant effect of SDB syndrome on growth parameters (weight-for-age parameter z-score and BMI for age z-score) was observed among males. Concerning the weight for age z-score, a significant difference was found between the means of control and SDB individuals (P = 0.0302). In male groups, the difference was significant (P=0.043), while non-significant difference was found in female groups (P = 0.69)., Conclusion: This study highlights a significant effect of SDB on growth parameters among males aged between 3 and 12 years., Competing Interests: There are no conflicts of interest., (© 2023 Micheline Katramiz, Antoine Saadé, Mode Al Ojaimi, Mona Nahas Gholmieh.)

We report four children from three related families who presented with a similar phenotype characterized by developmental delay, hypotonia, seizures, failure-to-thrive, strabismus, drooling, recurrent otitis media, hearing impairment, and genitourinary malformations. They also shared common facial features including arched eyebrows, prominent eyes, broad nasal bridge, low-hanging columella, open mouth, thick lower lip, protruding tongue, large low-set ears, and parietal bossing. Exome sequencing for affected individuals revealed a homozygous frame-shift variant, c.1833del; p.(Thr612Glnfs*22), in PROSER1 which encodes the proline and serine rich protein 1 (PROSER1). PROSER1 has recently been found to be part of the histone methyltransferases KMT2C/KMT2D complexes. PROSER1 stabilizes TET2, a member of the TET family of DNA demethylases which is involved in recruiting the enhancer-associated KMT2C/KMT2D complexes and mediating DNA demethylation, activating gene expression. Therefore, PROSER1 may play vital and potentially general roles in gene regulation, consistent with the wide phenotypic spectrum observed in the individuals presented here. The consistent phenotype, the loss-of-function predicted from the frame-shift, the co-segregation of the phenotype in our large pedigree, the vital role of PROSER1 in gene regulation, and the association of related genes with neurodevelopmental disorders argue for the loss of PROSER1 to be the cause for a novel recognizable syndrome., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)