More than 50% of children with tuberous sclerosis complex (TSC) suffer from developmental delay, cognitive impairment, and autism spectrum disorders (ASD). These disorders, which as a whole are considered "neurodevelopmental disorders," can cause a tremendous burden, over and above the time and cost of having a child with TSC. These children often need lifelong support, and the treatments can be extremely expensive and time-consuming. Early intervention is very important to help improve developmental outcomes. The best way to design effective early interventions is to predict developmental disorders before they are diagnosed (in infancy) and to understand the exact cause of neurodevelopmental disorders. No studies have prospectively investigated the exact predictors or causes of neurodevelopmental disorders in TSC.

Our goal is to investigate and define predictors of neurodevelopmental disorders, namely ASD and cognitive impairment, in infants with TSC before the actual diagnoses are made. Because TSC is often diagnosed before birth, and children are followed throughout their infancy and childhood, a study of this kind is feasible and clinically necessary. Based on findings from both the University of California, Los Angeles (UCLA) and Children's Hospital, Boston, we believe that we will be able to detect early markers of ASD and cognitive impairment in these infants.

We have three specific goals: (1) To predict the development of ASD and cognitive impairment in children with TSC before age 3. (2) To describe pathways to ASD and cognitive impairment in children with TSC. (3) To better define the characteristics of ASD in children with TSC in order to better understand which treatments may be most effective for these children.

We propose to enroll infants with TSC at age 3-6 months, and then to follow them at ages 9, 12, 18, 24, and 36 months. At 36 months, diagnostic testing for ASD and cognitive impairment will be performed. At each prior age, we will perform comprehensive testing that includes behavioral measures (such as language and motor testing, assessment of play and observation of mother-child interaction), brain imaging, and electroencephalography (EEG). We will conduct this study at two sites, UCLA and CHB, as both have large TSC programs as well as resources and expertise in all of the measures that are going to be used.

Once we are better able to understand the early predictors and exact pathways to cognitive impairment and ASD in children with TSC, we will be able to design and implement more effective, early treatments that will ultimately lead to better outcomes for these children.