Non-Specific Inherited Background Susceptibilities for Autism Spectrum Disorder
Objectives: In this talk, both direct genetic effects as well as non-ASD-specific inherited background susceptibilities that amplify the level of ASD impairment will be discussed.
Methods: The first part of this talk describes a retrospective study in 114 males with a clinical diagnosis of ASD and 114 of their male siblings. In all children, quantitative autistic traits (QAT) were assessed, as well as ADHD symptoms and motor coordination. We examined the extent to which these two—non-ASD-specific—neurodevelopmental traits might contribute to ASD recurrence in the siblings. The second part of this talk portrays the direct genetic effect, and describes (preliminary) data on the neurodevelopmental profile (including ASD and ADHD traits) of children with rare monogenic syndromes, such as Fragile X syndrome, Tuberous Sclerosis Complex and Neurofibromatosis type I.
Results: In siblings of ASD-affected probands over 50% of the variation in autistic impairment—whether ascertained quantitatively or categorically—was predicted by sibling ADHD and motor problems. Preliminary data in children with rare monogenic syndromes demonstrates that neurodevelopmental difficulties such as ASD and ADHD are highly prevalent and often co-occur in these patients.
Conclusions: These studies suggest that background ASD susceptibilities that are inherited but non-specific (“BASINS”) play a significant role in the development of ASD, and may contribute to additive genetic liability in the same manner that ASD-specific susceptibilities (such as deleterious mutations) engender ASD risk (Figure 1).