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Updated: Jan 20, 2026
Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
Published on: June 10, 2017
Exome sequencing in patients with antiepileptic drug exposure and complex phenotypes
Adam Jackson1, Heather Ward2, Rebecca Louise Bromley3,4
1Blackpool Teaching Hospitals NHS Trust, Blackpool, UK adam.jackson@doctors.org.uk.
Insights
Genetic testing, including whole exome sequencing, can identify alternative diagnoses in children with suspected Fetal Anticonvulsant Syndrome (FACS). This aids in accurate diagnosis and management for infants exposed to antiepileptic drugs (AEDs) during pregnancy.
Area of Science:
- Genetics
- Pediatrics
- Clinical Diagnostics
Background:
- Fetal Anticonvulsant Syndrome (FACS) is a clinical diagnosis for developmental issues in children exposed to antiepileptic drugs (AEDs) in utero.
- Excluding genetic disorders is crucial for accurate FACS diagnosis and management.
Purpose of the Study:
- To investigate the utility of exome sequencing in identifying genetic causes for developmental disorders in children exposed to AEDs in utero.
- To determine if genetic variants can explain phenotypes in children suspected of having FACS but with alternative diagnoses.
Main Methods:
- Exome sequencing data from 42 children exposed to AEDs in utero (Deciphering Developmental Disorders Study) were analyzed.
- Chromosome microarray data from 10 children with FACS were reviewed.
- Pathogenicity of identified variants was assessed in relation to developmental disorder genes.
Main Results:
- Seven children (17%) in the DDD study had pathogenic variants explaining their phenotype.
- Variants were identified in 13% of valproate-exposed and 21% of carbamazepine-exposed cases.
- No pathogenic copy number variants were found in the local sample of 10 patients.
Conclusions:
- Whole exome sequencing identified alternative genetic diagnoses in a significant proportion of children exposed to AEDs in utero.
- These findings impact genetic counseling and clinical management for affected families.
- Whole exome sequencing should be considered in the diagnostic workup for children exposed to AEDs in utero.
Introduction:
Fetal anticonvulsant syndrome (FACS) describes the pattern of physical and developmental problems seen in those children exposed to certain antiepileptic drugs (AEDs) in utero. The diagnosis of FACS is a clinical one and so excluding alternative diagnoses such as genetic disorders is essential.
Methods:
We reviewed the pathogenicity of reported variants identified on exome sequencing in the Deciphering Developmental Disorders (DDD) Study in 42 children exposed to AEDs in utero, but where a diagnosis other than FACS was suspected. In addition, we analysed chromosome microarray data from 10 patients with FACS seen in a Regional Genetics Service.
Results:
Seven children (17%) from the DDD Study had a copy number variant or pathogenic variant in a developmental disorder gene which was considered to explain or partially explain their phenotype. Across the AED exposure types, variants were found in 2/15 (13%) valproate exposed cases and 3/14 (21%) carbamazepine exposed cases. No pathogenic copy number variants were identified in our local sample (n=10).
Conclusions:
This study is the first of its kind to analyse the exomes of children with developmental disorders who were exposed to AEDs in utero. Though we acknowledge that the results are subject to bias, a significant number of children were identified with alternate diagnoses which had an impact on counselling and management. We suggest that consideration is given to performing whole exome sequencing as part of the diagnostic work-up for children exposed to AEDs in utero.
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