Diagnosing neurodevelopmental disorders using whole genome sequencing

neurodevelopmental disorders


As we prepare for the American Academy of Neurology (AAN) annual meeting in Los Angeles next week, we’ve been reviewing the benefits of clinical whole genome sequencing (WGS) that are helping to diagnose and characterize neurodevelopmental disorders.

Neurodevelopmental disorders are frequently identified in early childhood and persist throughout adulthood. They typically include, but are not limited to, intellectual disability (ID), developmental disability (DD), autism spectrum disorders (ASD) and epilepsy. They’re often characterized by heterogeneous phenotypes that make diagnosis difficult. Here are some common scenarios complicating diagnosis:

  • A single patient may present multiple co-occurring phenotypes
  • Multiple patients may share an underlying genetic etiology, but exhibit varying degrees of penetrance or expressivity of a phenotype
  • Many known neurodevelopmental disorder disease genes are associated with multiple disorders

Clinical WGS offers an unbiased approach that avoids the limitations associated with targeted gene panel assays where only selected genes are considered. Using WGS, all mutations can be identified and assessed in a single sequencing run against a broad phenotypic spectrum.

At the same time, as more diagnosed cases are published, it has become increasingly evident that a significant number of neurodevelopmental disorders are caused by copy number variants (CNVs). Clinical WGS provides a more complete view of small sequence changes (SNVs and indels) plus CNVs, including those that are simultaneously too small to be identified by standard microarray analysis and too large to be identified by exome or more targeted NGS analysis.

The result of identifying more relevant mutations via WGS can only be a higher diagnostic yield.

If you’re heading to the AAN annual meeting next week in Los Angeles, California, stop by booth #907 where we can continue the discussion.


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