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[Genetic studies and neurodevelopment. From effectiveness to genetic models].

Beatriz Calleja-Pérez1, Ana L Fernández-Perrone2, Daniel M Fernández-Mayoralas2

  • 1Atención Primaria de Pediatría, Centro de Salud Doctor Cirajas, España.

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|March 10, 2020
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Summary

Genetic advances confirm a strong hereditary basis for neurodevelopmental disorders (NDD). Advanced sequencing techniques significantly improve etiological diagnosis rates for NDD, surpassing older methods.

Keywords:
arraysautismgeneticsintellectual disabilityneurodevelopmental disorderssequencing

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Area of Science:

  • Genetics and Genomics
  • Neurodevelopmental Disorders
  • Clinical Diagnostics

Background:

  • Neurodevelopmental disorders (NDDs) have a significant hereditary component, increasingly supported by genetic research.
  • Early genetic studies highlighted the substantial contribution of genotypic variation to NDDs.
  • Genetic testing is crucial for etiological diagnosis in clinical practice for NDDs.

Purpose of the Study:

  • To evaluate the evolving role and effectiveness of genetic studies in diagnosing neurodevelopmental disorders.
  • To compare the diagnostic yield of various genetic techniques, from cytogenetics to advanced sequencing.
  • To assess the impact of new genetic knowledge on diagnostic algorithms and theoretical models for NDDs.

Main Methods:

  • Review of genetic studies focusing on heritability, linkage, and association in NDDs.
  • Comparison of diagnostic effectiveness between array comparative genomic hybridization and historical cytogenetic techniques.
  • Analysis of the impact of exome and genome sequencing (trio analysis) on diagnostic rates.

Main Results:

  • Array comparative genomic hybridization offers improved diagnostic effectiveness (10%) over historical cytogenetic techniques (3%) for NDDs.
  • Molecular genetic sequencing techniques, particularly exome and genome sequencing in trio, achieve significantly higher diagnostic rates (30-50%).
  • Increased identification of causal variants is prompting revisions of existing polygenic theoretical models for NDDs.

Conclusions:

  • Advanced genetic sequencing technologies are revolutionizing the etiological diagnosis of neurodevelopmental disorders.
  • The diagnostic algorithms for NDDs are being reshaped by the success and accessibility of whole-exome and whole-genome sequencing.
  • Current genetic findings are refining our understanding of the genetic architecture underlying conditions like intellectual disability and autism.