Genetic Abnormalities in Neurodevelopmental Disorders with Multidimensional Impairment.
Cyril Hanin1,2,3, Paloma Torres1,2, Isabelle Millet1,2
1Department of Child and Adolescent Psychiatry, Assistance Publique-Hôpitaux de Paris,, Sorbonne University, Paris, France.
Journal of Molecular Neuroscience : MN
|October 2, 2025
Summary
Genetic testing reveals frequent abnormalities in children with complex neurodevelopmental disorders (NDD) lacking a specific diagnosis. This highlights the need for systematic genetic assessment in these challenging cases.
Area of Science:
- Genetics
- Neurodevelopmental Disorders
- Clinical Diagnostics
Background:
- Children with neurodevelopmental disorders (NDD) often present with complex, multidimensional impairments.
- Current diagnostic criteria (DSM-5) lack a category for such cases, leaving them "diagnostically homeless."
- Investigating genetic causes is crucial for understanding these complex NDD presentations.
Purpose of the Study:
- To determine the prevalence of genetic abnormalities in children with complex NDD and multidimensional impairments.
- To explore potential associations between clinical dimensions and genetic findings in this population.
Main Methods:
- Diagnosed Multidimensional Impairment (MDI) in 666 patients between 2017-2019.
- Performed genetic assessments on 122 patients, including DNA microarrays, karyotyping, gene panels, FISH, FMR1 testing, and exome/genome sequencing.
- Utilized univariate analyses and clustering to analyze data.
Main Results:
- Identified genetic abnormalities in 78 out of 122 patients (64%).
- Findings included known NDD-associated abnormalities (41), mutations linked to severe ASD/ID (16), novel abnormalities (11), and variants of uncertain significance (10).
- No association was found between clinical dimensions/severity clusters and the presence of genetic abnormalities.
Conclusions:
- A high rate of genetic findings (47-64%) was observed in children with complex NDD and multidimensional impairment.
- This underscores the necessity for systematic genetic testing in this patient group.
- Referral bias towards severe cases was noted, yet genetic findings remain significant.
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