Neurogenetic disorders across the lifespan: from aberrant development to degeneration

Intellectual disability and autism spectrum disorder (ASD) are common, and genetic testing is increasingly performed in individuals with these diagnoses to inform prognosis, refine management and provide information about recurrence risk in the family. For neurogenetic conditions associated with intellectual disability and ASD, data on natural history in adults are scarce; however, as older adults with these disorders are identified, it is becoming clear that some conditions are associated with both neurodevelopmental problems and neurodegeneration. Moreover, emerging evidence indicates that some neurogenetic conditions associated primarily with neurodegeneration also affect neurodevelopment. In this Perspective, we discuss examples of diseases that have developmental and degenerative overlap. We propose that neurogenetic disorders should be studied continually across the lifespan to understand the roles of the affected genes in brain development and maintenance, and to inform strategies for treatment. Traditionally, CNS diseases have been classified into early-onset neurodevelopmental disorders and late-onset neurodegenerative disorders. However, as this article highlights, we now recognize that developmental and neurodegenerative disorders can involve shared mechanisms, with some classic neurodegenerative diseases also having a neurodevelopmental component.

Automated summary

Intellectual disability and autism spectrum disorder are common, with genetic testing now being used more frequently to provide information. Data on the natural history of neurogenetic conditions in adults are limited, highlighting the need for lifelong studies on affected genes. There is recognition that some neurodegenerative disorders may also involve neurodevelopmental components.