phenylephrine-hydrochloride and Neurodevelopmental-Disorders

To conduct a systematic review and meta-analysis of the association between children and adolescents with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) and ocular characteristics. Systematic review with meta-analysis. Six databases (PubMed, Scopus, APA PsycInfo, Embase, EBSCOhost, and Cochrane library) were selected for a systematic literature search from database inception to July 2022. The observational studies assessing and reporting at least one outcome regarding ocular characteristics in children and adolescents with ADHD or ASD aged 6-17 were included. Studies in languages other than English, studies of adult or elderly human populations, and animal studies were excluded. The results were analyzed following the PRISMA guideline 2020. The findings of 15 studies, including 433 participants with ADHD, 253 participants with ASD, and 514 participants with typical development (TD), revealed that there were no significant differences in retinal nerve fiber layer, ganglion cell complex, and macular thickness between the ADHD group and the TD group. In subgroup analysis, significant differences in inferior ganglion cell (MD = - 3.19; 95% CI = [- 6.06, - 0.31], p = 0.03) and nasal macular thickness (MD = 5.88; 95% CI = [- 0.01, 11.76], p = 0.05) were detected between the ADHD group and the TD group. A significant difference in pupillary light reflex (PLR) was also observed between the ASD group and the TD group (MD = 29.7; 95% CI = [18.79, 40.63], p < 0.001). Existing evidence suggests a possible association between children and adolescents with ADHD or ASD and ocular characteristics. Given the limited number of studies, further research on a larger cohort is necessary to claim a possible diagnosis of ADHD or ASD through ocular characteristics.

Topics: Adolescent; Adult; Aged; Animals; Autism Spectrum Disorder; Child; Face; Humans; Neurodevelopmental Disorders; Nose; Retina

The ubiquitin-proteasome system facilitates the degradation of unstable or damaged proteins. UBR1-7, which are members of hundreds of E3 ubiquitin ligases, recognize and regulate the half-life of specific proteins on the basis of their N-terminal sequences ("N-end rule"). In seven individuals with intellectual disability, epilepsy, ptosis, hypothyroidism, and genital anomalies, we uncovered bi-allelic variants in UBR7. Their phenotype differs significantly from that of Johanson-Blizzard syndrome (JBS), which is caused by bi-allelic variants in UBR1, notably by the presence of epilepsy and the absence of exocrine pancreatic insufficiency and hypoplasia of nasal alae. While the mechanistic etiology of JBS remains uncertain, mutation of both Ubr1 and Ubr2 in the mouse or of the C. elegans UBR5 ortholog results in Notch signaling defects. Consistent with a potential role in Notch signaling, C. elegans ubr-7 expression partially overlaps with that of ubr-5, including in neurons, as well as the distal tip cell that plays a crucial role in signaling to germline stem cells via the Notch signaling pathway. Analysis of ubr-5 and ubr-7 single mutants and double mutants revealed genetic interactions with the Notch receptor gene glp-1 that influenced development and embryo formation. Collectively, our findings further implicate the UBR protein family and the Notch signaling pathway in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism that differs from JBS. Further studies exploring a potential role in histone regulation are warranted given clinical overlap with KAT6B disorders and the interaction of UBR7 and UBR5 with histones.

Topics: Animals; Anus, Imperforate; Caenorhabditis elegans; Cell Line; Ectodermal Dysplasia; Epilepsy; Growth Disorders; Hearing Loss, Sensorineural; HEK293 Cells; Histones; Humans; Hypothyroidism; Intellectual Disability; Mice; Mutation; Neurodevelopmental Disorders; Nose; Pancreatic Diseases; Proteasome Endopeptidase Complex; Receptors, Notch; Signal Transduction; Ubiquitin-Protein Ligases

Okur-Chung neurodevelopmental syndrome (OCNDS) and tricho-rhino-phalangeal syndrome type I (TRPSI) are rare Mendelian diseases. OCNDS is caused by CSNK2A1 gene variants and TRPSI is caused by the TRPS1gene. However, to have two Mendelian diseases in one patient is even rarer.. A 6-year-10-month-old boy characterized by special facial features, short stature and mental retardation was referred to our pediatric endocrinology department. Whole-exome sequencing (WES) was done to detect the molecular basis of his disease. This patient was confirmed to carry two variants in the CSNK2A1 gene and one in the TRPS1 gene. The variant in the CSNK2A1 gene was vertically transmitted from his father, and the variant in TRPS1 gene from his mother. These two variants are classified as pathogenic and the causes of the presentation in this child. This patient's father and mother have subsequently been diagnosed as having OCNDS and TRPSI respectively.. This is the first reported case of a dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in the same patient. This patient is the first published example of vertical transmission of this recurrent CSN2A1 variant from parent to child. A novel variant in the TRPS1 gene that is pathogenic was also identified. In conclusion, identification of the variants in this patient expands the phenotypes and molecular basis of dual Mendelian diseases.

Topics: Asian People; Base Sequence; Child; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Neurodevelopmental Disorders; Nose; Pedigree