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Bainbridge-Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the ASXL3 gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype-phenotype correlation. We identified 19 ASXL3 variants, nine of which are novel. We documented recurrence in nontwin siblings due to parental mosaicism. The predominant prenatal finding was intrauterine growth restriction (35%) followed, after birth, by feeding difficulties (90.5%), hypotonia (85.7%), and gastroesophageal reflux disease (82.4%). Later in life, intellectual disability, language impairment, autism spectrum disorder (75%), and joint laxity (73.7%) were noted. Individuals with variants in the 3' mutational cluster region (MCR) of exon 12 exhibited more perinatal feeding problems, and those with variants in the 5' MCR of exon 11 displayed lower percentiles in height and occipitofrontal circumference, as well as higher frequency of arched eyebrows. This study is the first characterization of a Spanish BRPS cohort, with more than 50 clinical features analyzed, representing the most detailed phenotypic analysis to date., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bainbridge-Ropers syndrome (BRPS) or additional sex combs-like 3 (ASXL3)-related disorder is a neurodevelopmental disorder caused by a de novo missense mutation in the ASXL3 gene found on chromosome 18. The number of BRPS cases recorded to date is less than 100. In this report, a six-year-old Texan boy with global developmental delay, aggressive behavior, insomnia, microcephaly, strabismus, facial dysmorphic features, vesicoureteral reflux (VUR), bilateral congenital renal dysplasia, gastroesophageal reflux disease (GERD), hypotonia, failure to thrive, dysphagia, and status post-gastrostomy tube was referred to Children's Health in Dallas for evaluation. The patient shares a chromosomal abnormality with his father that did not explain his clinical findings. Therefore, further tests were indicated and a whole-exome gene sequencing revealed a de novo pathogenic heterozygous mutation in the ASXL3 gene in chromosome 18q12.1 associated with autosomal dominant BRPS. To our knowledge, this is the first case of BRPS with bilateral congenital renal dysplasia and may be correlated to the presence of the ASXL3 gene in renal tissue. This discovery provides significant new information about this condition that might be essential for comprehending it., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Siu Xiao et al.)

The study aimed at widening the clinical and genetic spectrum of ASXL3-related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3-related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3-related syndrome, we define its natural history and clinical evolution occurring with age. We report familial ASXL3 pathogenic variants, characterize the phenotype in mildly affected individuals and discuss nonpenetrance. We also discuss the role of missense variants in ASXL3. We delineate a variable but consistent phenotype. The most characteristic features are neurodevelopmental delay with consistently limited speech, significant neuro-behavioral issues, hypotonia, and feeding difficulties. Distinctive features include downslanting palpebral fissures, hypertelorism, tubular nose with a prominent nasal bridge, and low-hanging columella. The presented data will inform clinical management of individuals with ASXL3-related syndrome and improve interpretation of new ASXL3 sequence variants., (© 2021 Wiley Periodicals LLC.)

Bainbridge-Ropers syndrome (BRPS) [OMIM#615485] is a neurodevelopmental disorder, characterized by delayed psychomotor development with generalized hypotonia, intellectual disability with poor or absent speech, feeding difficulties, growth failure, specific craniofacial and minor skeletal features. It was firstly reported in 2013 by Bainbridge et al., who observed a group of individuals sharing overlapping features with Bohring-Opitz syndrome which were caused by pathogenic variant in ASXL1, who indeed carried truncating mutations in ASXL3. To date, 33 cases were described in the literature. BRPS is caused by loss-of-function mutations in ASXL3 which are mostly located in two mutational cluster regions (MCR). The exact molecular mechanism of these mutations resulting in the disease phenotype is still uncertain due to the observation of LOF mutations in healthy population. Here, we report four individuals with BRPS carrying de novo LOF mutations in ASXL3, comparing and summarizing the clinical phenotype of all BRPS reported so far. Furthermore, we try to dissect the genotype-phenotype correlation among the two well reported MCRs in all BRPS from the literature., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Bromophenols (BRPs) have been widely detected in human tissues, however, relative proportions from natural products and/or anthropogenic flame retardants are not clear. 21 polybrominated diphenyl ethers (PBDEs), 15 MeO/OH-PBDEs, and 10 BRPs were simultaneously quantified in adipose collected from people from New York City, USA. An in vitro assay utilizing human liver microsomes was performed for detected predominant organobromine. High concentrations of 2,4,6-triBRP and PBDEs were observed, and extremely low concentrations of naturally occurring MeO/OH-PBDEs were detected. Similar biotransformatioin rates of BRPs and MeO/OH-PBDEs indicated that the relative high concentration of 2,4,6-triBRP in humans was not of natural origin. Significant correlation observed between concentrations of 2,4,6-triBRP and BDE-209 suggested that the two chemicals may share a common source. Both 2,4,6-triBRP and BDE-209 were detected in commercial ABS resins, suggesting that plastic products made from ABS resins could be potential sources of co-exposure of the two compounds for humans., (Copyright © 2015 Elsevier Ltd. All rights reserved.)