Genetics, early-life factors and brain imaging in children with autism spectrum disorder
P. Querol Clares, M. Alijotas Capdevila, M. Martinez Ramirez, I. Setien Ramos, J. Lugo Marin, A. G. Lungo Peccorini, L. Gisbert Gustemps, J. A. Ramos QuirogaIntroduction
Autism spectrum disorder (ASD) is a neurodevelopmental disorder influenced by common polygenic variation, rare high-impact genetic variants, and non-genetic factors. Gene–environment interactions are increasingly recognized as potentially relevant, although their precise role in ASD heterogeneity and variable expression remains incompletely understood. However, current research seldom provides a joint description of genetic, early-life factors, and clinical features, highlighting the need for more comprehensive studies.
Objectives
To analyze prenatal, perinatal, and postnatal factors, along with clinical characteristics and findings from complementary assessments in a cohort of children with ASD.
Methods
A cross-sectional study was conducted at a Child and Adolescent ASD unit in a tertiary hospital. Inclusion criteria were a DSM-5 diagnosis of ASD and age up to 18 years. The exclusion criterion was insufficient information according to the study objectives. Of the 260 patients under follow-up, 224 were included in the analysis. Data collection encompassed prenatal, perinatal, and postnatal factors, clinical characteristics and findings from complementary investigations.
Results
The study sample comprised 78% male and 22% female patients. The mean age was 9.8 years, with the majority falling between 5 and 10 years (48%), and the remainder distributed as 22% aged 11–15, 16% >15, and 14% <5 years. Regarding ASD severity, 53% of patients were classified as grade 1, 30% as grade 2, and 17% as grade 3. In addition, 41% had intellectual disability (mild:65%, moderate:23%, severe:12%) while 80% showed early childhood language impairments.
Concerning prenatal factors, mean maternal and paternal ages were 34 and 36 years, with most parents in the 30–39 year range (67% and 58%, respectively). Attention-deficit/hyperactivity disorder was the most frequently reported familial comorbidity, present in 86% of cases. Perinatal factors included cesarean delivery(31%), prematurity(21%) and eclampsia/preeclampsia(7%). Postnatal data showed a mean birth weight of 2870 g, with 22% classified as low birth weight (<2500 g).
Complementary investigations revealed pathological findings in 11% of genomic arrays, 9% of exome analyses and abnormal brain MRI in 86% of patients. Genetic testing predominantly yielded non-diagnostic results or variants of uncertain significance, with a higher pathogenic yield from copy number variants than from exome sequencing. ASD-relevant findings included NRXN1 deletions, SHANK3 variants, 16p11.2 duplications, 22q11.2 rearrangements and sex chromosome aneuploidies.
Conclusions
This cross-sectional study underscores that ASD is frequently associated with early-life complications, language impairments and neuroimaging abnormalities, while genetic testing yields both pathogenic and inconclusive findings. These findings reinforce the need for integrative approaches to advance precision in ASD.
Disclosure of Interest
None Declared