A case of child survivor of family trauma: creating a safe place, building strengths through play

Young children living in dysfunctional households marked with high levels of interparental domestic violence are at higher risk for developing future psychiatric disorders and overall health problems. Successful treatment interventions with this group are varied, although existing research highlights the need for treatments that adopt a strength-based approach, that promote safety, and that nurture interpersonal relationships. Child-centred play therapy provides the client with a sense of empowerment and is described in this chapter

Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta

PurposeDominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.MethodsWe used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.ResultsWe found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment.ConclusionOur study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity