From Infancy to Early School Age: Longitudinal Developmental Outcomes and Autism Diagnostic Stability in Tuberous...

Tuberous sclerosis complex (TSC) is associated with intellectual disability (ID), autism spectrum disorder (ASD), and TSC-associated neuropsychiatric disorders. Early prospective studies have characterized neurodevelopmental outcomes in infants and toddlers with TSC. Leveraging longitudinal data from the TSC Autism Center of Excellence Research Network and the Rare Diseases Clinical Research Network, we examined longer-term developmental trajectories and ASD diagnostic stability in a cohort of children with TSC.

Participants were originally enrolled in TSC Autism Center of Excellence Research Network and followed through 36 months and then subsequently enrolled in Rare Diseases Clinical Research Network for continued follow-up. Longitudinal neurodevelopmental assessments were performed. Analyses focused on participants' most recent assessment to accommodate study overlap and missing data. Outcomes were compared by ASD status, sex, and adaptive functioning.

Thirty-two participants with TSC (50% female; mean age 4.5 years) were included. Cognitive and adaptive functioning scores were generally in the delayed range and remained relatively stable over time. At the most recent visit, 48% met criteria for ASD, with ASD diagnosis remaining stable in most participants. Lower adaptive functioning was significantly associated with ASD diagnosis (P = 0.016) and greater social and behavioral impairment. Females demonstrated significantly higher levels of social impairment on the Social Responsiveness Scale, Second Edition compared to males, even after adjusting for ASD diagnosis.

Early cognitive and adaptive assessments in children with TSC inform later neurodevelopmental outcomes. While ASD diagnosis is largely stable over time, subtle social impairments may be under-recognized. Routine, longitudinal screening for TSC-associated neuropsychiatric disorders symptoms is essential to support timely identification and intervention in TSC.