Highlights d Scene-selective cortex responds more to scenes than objects or faces by age 5 d Scene motion responses in OPA are not present by age 5 and only emerge by age 8 d Developmental changes are not found in MT, PPA, or RSC

High-impact genetic variants associated with neurodevelopmental disorders provide biologically defined entry points for etiological discovery. The 3q29 deletion (3q29Del) is one such variant that confers a ~40-fold increased risk for schizophrenia, and a ~30-fold increased risk for autism. However, the specific neural mechanisms underlying this link remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in 3q29Del subjects (N = 24) and healthy controls (N = 1,608) using structural MRI. Given prior reports of posterior fossa abnormalities in 3q29Del, we focus our investigation on the cerebellum and its primary tissue-types. Additionally, we compare the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del subjects and controls, and examine the association between neuroanatomical findings and standardized behavioral measures to probe gene-brain-behavior relationships. 3q29Del subjects had smaller cerebellar cortex volumes than controls, both before and after correction for intracranial volume (ICV). 3q29Del subjects also had larger cerebellar white matter volumes than controls following ICV-correction. The 3q29Del group displayed an elevated rate of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Sex played a moderating role in a subset of findings. Cerebellar white matter volume was positively associated with visual-motor integration skills and cognitive ability, while cystic/cyst-like malformations yielded no behavioral link. Abnormal development of posterior fossa structures may represent neuroimaging-based biomarkers in 3q29Del. Results reveal cerebellar associations with sensorimotor and cognitive deficits in 3q29Del and present a novel point of genetic convergence with cerebellar pathology reported in idiopathic forms of neurodevelopmental disease.

Background The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and neuropsychiatric phenotypes, including a 19-fold increased risk for autism spectrum disorder (ASD). Previous work by our team identified elevated social disability in this population via parent-report questionnaires. However, clinical features of ASD in this population have not been explored in detail. Methods Thirty-one individuals with 3q29 deletion syndrome (3q29del, 61.3% male) were evaluated using two gold-standard clinical ASD evaluations: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the Autism Diagnostic Interview, Revised (ADI-R). Four matched comparators for each subject were ascertained from the National Database for Autism Research. Item-level scores on the ADOS-2 and ADI-R were compared between subjects with 3q29del and matched comparators. Results Subjects with 3q29del and no ASD (3q29del-ASD) had greater evidence of social disability compared to typically developing (TD) comparison subjects across the ADOS-2. Subjects with 3q29del and ASD (3q29del + ASD) were largely indistinguishable from non-syndromic ASD (nsASD) subjects on the ADOS-2. 3q29del + ASD performed significantly better on social communication on the ADI-R than nsASD (3q29 + ASD mean = 11.36; nsASD mean = 15.70; p = 0.01), and this was driven by reduced deficits in nonverbal communication (3q29 + ASD mean = 1.73; nsASD mean = 3.63; p = 0.03). 3q29del + ASD reported significantly later age at the first two-word phrase compared to nsASD (3q29del + ASD mean = 43.89 months; nsASD mean = 37.86 months; p = 0.01). However, speech delay was not related to improved nonverbal communication in 3q29del + ASD. Limitations There were not enough TD comparators with ADI-R data in NDAR to include in the present analysis. Additionally, our relatively small sample size made it difficult to assess race and ethnicity effects. Conclusions 3q29del is associated with significant social disability, irrespective of ASD diagnosis. 3q29del + ASD have similar levels of social disability to nsASD, while 3q29del-ASD have significantly increased social disability compared to TD individuals. However, social communication is reasonably well preserved in 3q29del + ASD relative to nsASD. It is critical that verbal ability and social disability be examined separately in this population to ensure equal access to ASD and social skills evaluations and services.