Diagnostic Value of Exome Analysis in Patients with Mental Retardation

Background: In patients with global developmental disorder, mental retardation and/or autism spectrum disorder, exome analysis internationally is diagnostic standard. Since January 2021, in Germany, the restriction to 25 kb in the EBM (Einheitlicher Bewertungsmaßstab) has been lifted. It is now possible to offer large panel or exome analysis to all patients if there is an appropriate indication.

Methods: Exome data collected during the first 6 months of children with mental retardation was evaluated retrospectively. The following questions were specifically addressed: What is basic diagnostics? What detection rate can be expected? What is the significance of parental data sets (Trio) and standardized information on the individual phenotype, the HPO (human phenotype ontology) terms? What are the consequences of diagnoses made?

Results: Evaluation of 97 exome analyses with HPO “global developmental delay” showed that it was possible to resolve and confirm a reliable genetic diagnosis with defined inheritance pattern and recurrence risk in 32% of cases. Another 32 harbored sequence variants which, in combination with the clinical picture, were assessed as possibly causative, but could currently not be classified as definitely pathogenic without further investigations (e.g., segregation). In the smaller subgroup of trio exome analyses, the number of questionably disease-causing variants was lower.

Conclusion: After chromosomal microarray and exclusion of fragile X syndrome, exome analysis is a diagnostic tool with a high elucidation rate. Genetic diagnosis allows estimation of prognosis, associated disease and recurrence risk, influencing clinical management and enables disease-specific support resources for patients/families.

Publication History

Article published online:
28 October 2021