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

Veronica Frewer; Courtney P Gilchrist; Simonne E Collins; Katrina Williams; Marc L Seal; Richard J Leventer; David J Amor

doi:10.1111/jcpp.13510

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

J Child Psychol Psychiatry. 2021 Nov;62(11):1339-1352. doi: 10.1111/jcpp.13510. Epub 2021 Aug 23.

Authors

Veronica Frewer^{1

2}, Courtney P Gilchrist^{1

3}, Simonne E Collins^{1

4}, Katrina Williams^{5

6}, Marc L Seal^{1

2}, Richard J Leventer^{1

2

7}, David J Amor^{1

2

7}

Affiliations

¹ Murdoch Children's Research Institute, Parkville, Vic., Australia.
² Department of Paediatrics, The University of Melbourne, Parkville, Vic., Australia.
³ Neurodevelopment in Health and Disease, RMIT University, Bundoora, Vic., Australia.
⁴ School of Psychological Sciences, Turner Institute for Brain & Mental Health, Monash University, Melbourne, Vic., Australia.
⁵ Monash University, Melbourne, Vic., Australia.
⁶ Monash Children's Hospital, Melbourne, Vic., Australia.
⁷ Royal Children's Hospital, Parkville, Vic., Australia.

PMID: 34426966
DOI: 10.1111/jcpp.13510

Abstract

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.

Keywords: Autism spectrum disorder; MRI; magnetic resonance imaging; monogenic disorders.

Publication types

Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Autism Spectrum Disorder* / diagnostic imaging
Autism Spectrum Disorder* / genetics
Autistic Disorder*
Brain / diagnostic imaging
Humans
Magnetic Resonance Imaging
Neuroimaging