A systematic review of brain MRI findings in monogenic disorders strongly associated with autism spectrum disorder.

BACKGROUND: Research on monogenic forms of autism spectrum disorder (autism) can inform our understanding of genetic contributions to the autism phenotype; yet, there is much to be learned about the pathways from gene to brain structure to behavior. This systematic review summarizes and evaluates research on brain magnetic resonance imaging (MRI) findings in monogenic conditions that have strong association with autism. This will improve understanding of the impact of genetic variability on brain structure and related behavioral traits in autism. METHODS: The search strategy for this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias (ROB) assessment was completed on included studies using the Newcastle-Ottawa Scales. RESULTS: Of 4,287 studies screened, 69 were included pertaining to 13 of the top 20 genes with the strongest association with autism. The greatest number of studies related to individuals with PTEN variants and autism. Brain MRI abnormalities were reported for 12 of the 13 genes studied, and in 51.7% of participants across all 13 genes, including 100% of participants with ARID1B variants. Specific MRI findings were highly variable, with no clear patterns emerging within or between the 13 genes, although white matter abnormalities were the most common. Few studies reported specific details about methods for acquisition and processing of brain MRI, and descriptors for brain abnormalities were variable. ROB assessment indicated high ROB for all studies, largely due to small sample sizes and lack of comparison groups. CONCLUSIONS: Brain abnormalities are common in this population of individuals, in particular, children; however, a range of different brain abnormalities were reported within and between genes. Directions for future neuroimaging research in monogenic autism are suggested.

Spoken Language Change in Children on the Autism Spectrum Receiving Community-Based Interventions.

We assessed the spoken language of 73 preschool aged children on the autism spectrum receiving community-based early intervention at two time points, approximately 7 months apart. Using the Spoken Language Benchmarks, there was a small non-significant change in the proportion of children transitioning from below, to at or above, Phase 3 (word combinations). Using binomial regression, a model comprising seven of nine clinician-proposed child-related predictors explained 64% of the variance. None of the predictors were individually significant, although a large effect size (OR = 16.71) was observed for children's baseline rate of communicative acts. The findings point to substantial unmet clinical need in children with minimal verbal language, but also the relevance of clinician-proposed predictors of their spoken language outcomes.

Prevalence and Age of Onset of Regression in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analytical Update.

A systematic review published in 2013 reported 32% of children on the autism spectrum experience skill loss, known as autistic regression. However, the frequency varied depending on definition and measures used to capture skills. Retrospective parent report and prospective observation indicate loss of language and/or social skills, with motor skills typically unaffected. Our aim was to update the prevalence and age of onset of autistic regression through a meta-analysis of the literature to understand if there have been changes to the reported onset and prevalence since 2010. A systematic literature search was conducted using Medline, Embase, PsycINFO, and the Cochrane Library databases and included studies published from 2010 onward. Risk of bias assessment was performed on included studies. A random effects model was used to calculate the pooled prevalence and age of onset of autistic regression. Ninety-seven studies were included in the systematic review, of which 75 studies involving 33,014 participants had sufficient data for meta-analytic syntheses. The pooled proportion of autistic regression was 30% (95% confidence interval [CI]: 27-32%) but heterogeneity was high (I2 = 96.91) and did not reduce with sensitivity or subgroup analyses based on study design or clinical differences, respectively. Prevalence varied according to risk of bias (low: 27%) and definition of regression (language: 20%, language/social: 40%, mixed: 30%, and unspecified: 27%). Weighted average age of onset was 19.8 months. Findings from this meta-analysis highlight the importance of developing a standardized definition of autistic regression, and tools to measure this at multiple time points during early childhood development. LAY SUMMARY: About a third of children with Autism Spectrum Disorder experience loss of skills, which is also known as autistic regression. This paper provides an update of the rate of autistic regression in children and the age when they first experience loss of skills, based on current studies. The findings from this review contribute to our understanding of the onset patterns of autistic regression. Unfortunately, studies are not sufficiently similar, making it difficult to provide clear answers on the exact timing or type of regression seen in different children.