This retrospective study aimed to specify the critical period for atypical brain development in individuals with autism spectrum disorder (ASD) using prenatal and postnatal head growth parameters. The sample consisted of 80 Caucasian, unrelated, idiopathic patients with ASD born after 1995. Fetal ultrasound parameters (head circumference [HC], abdominal circumference, and femur length) were obtained during the second and third trimesters of gestation. HC at birth and postnatal parameters at 12 and 24 months of age were also collected. Head overgrowth, assessed by HC, was highlighted during the second (20-26 weeks of amenorrhea) and third (28-36 weeks of amenorrhea) trimesters. Normal growth of body fetal parameters indicated that head overgrowth was not because of overall body overgrowth. Moreover, postnatal results replicated previously and reported head overgrowth. A critical time window for atypical brain development in autism is hypothesized to begin from the 22nd week of amenorrhea. This period is critical for cortical lamination and glial activation. A pathophysiological cascade is suggested with interactions between candidate genes and environmental factors.Lay Summary: It is now widely acknowledged in the scientific community, that autism is a neurodevelopmental disorder. Recent evidence from animal and pathological studies has implicated the in utero period. However, the precise time of onset of abnormal brain development remains unknown. This retrospective study reports novel findings, identifying an atypical head growth trajectory in children with autism, during the in utero period (after the 22nd week of amenorrhea). In the same children, postnatal head overgrowth was also observed. Late gestation is identified as a critical period for atypical brain development underlying autism symptoms.

Phelan–McDermid syndrome is related to terminal 22q13 deletions of various sizes affecting the SHANK3 gene. In this neurodevelopmental disorder, behavioural symptoms of autism spectrum disorder (ASD) are reported in half of cases. Extensive clinical and neurophysiological characterization is lacking to understand the genotype–phenotype correlation. Eighteen patients (8 males, mean age 12.7 years, SD = 9.2) with known 22q13 deletions were fully explored with determination of deletion size, along with behavioural, language and cognitive standardized assessments. Neurophysiological indices previously reported to be altered in autism (i.e., eye tracking in a social/non-social task and auditory evoked potential mismatch) were also recorded. Thirty-nine percent met ASD clinical criteria, exceeding cut-off scores on both ADI-R (Autism Diagnosis Interview based on the period spanning 4–5 years of age) and ADOS-2 (Autism Diagnosis Observation Schedule for the current period). All patients had intellectual disability and language disability. Deletion size was significantly correlated with expressive and receptive language disability but not with ASD standardized assessment scores. Developmental Quotient tended to be lower in patients with the largest deletions. Using Eye Tracking, smaller pupil size, which is typically described in ASD, was not observed in these patients. Furthermore, atypical shortened latency of mismatch negativity response previously reported in ASD was not observed, whereas the N250 pattern, related to language, was affected. Language disability combined with cognitive deficits may lead to autistic behavioural symptoms, but with different neurophysiological networks compared to typical autism. These results highlight the indication for early speech therapy rather than intensive autism programme to treat these patients.