GATOR1-related focal cortical dysplasia in epilepsy surgery patients and their families: A possible gradient in severity?
Language English Country Great Britain, England Media print-electronic
Document type Case Reports, Journal Article
PubMed
33461085
DOI
10.1016/j.ejpn.2020.12.001
PII: S1090-3798(20)30222-1
Knihovny.cz E-resources
- Keywords
- Epilepsy surgery, Focal cortical dysplasia, Focal epilepsy, GATOR1, Malformations of cortical development, Targeted gene panel sequencing,
- MeSH
- Child MeSH
- Phenotype MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Malformations of Cortical Development genetics surgery MeSH
- Adolescent MeSH
- Tumor Suppressor Proteins genetics MeSH
- GTPase-Activating Proteins genetics MeSH
- Drug Resistant Epilepsy genetics MeSH
- Retrospective Studies MeSH
- Germ-Line Mutation MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Names of Substances
- DEPDC5 protein, human MeSH Browser
- Tumor Suppressor Proteins MeSH
- NPRL2 protein, human MeSH Browser
- NPRL3 protein, human MeSH Browser
- GTPase-Activating Proteins MeSH
BACKGROUND: Variants of GATOR1-genes represent a recognised cause of focal cortical dysplasia (FCD), the most common structural aetiology in paediatric drug-resistant focal epilepsy. Reports on familial cases of GATOR1-associated FCD are limited, especially with respect to epilepsy surgery outcomes. METHODS: We present phenotypical manifestations of four unrelated patients with drug-resistant focal epilepsy, FCD and a first-degree relative with epilepsy. All patients underwent targeted gene panel sequencing as a part of the presurgical work up. Literature search was performed to compare our findings to previously published cases. RESULTS: The children (probands) had a more severe phenotype than their parents, including drug-resistant epilepsy and developmental delay, and they failed to achieve seizure freedom post-surgically. All patients had histopathologically confirmed FCD (types IIa, IIb, Ia). In Patient 1 and her affected father, we detected a known pathogenic NPRL2 variant. In patients 2 and 3 and their affected parents, we found novel likely pathogenic germline DEPDC5 variants. In family 4, we detected a novel variant in NPRL3. We identified 15 additional cases who underwent epilepsy surgery for GATOR1-associated FCD, with a positive family history of epilepsy in the literature; in 8/13 tested, the variant was inherited from an asymptomatic parent. CONCLUSION: The presented cases displayed a severity gradient in phenotype with children more severely affected than the parents. Although patients with GATOR1-associated FCD are considered good surgical candidates, post-surgical seizure outcome was poor in our familial cases, suggesting that accurate identification of the epileptogenic zone may be more challenging in this subgroup of patients.
Amsterdam UMC University of Amsterdam Department of Achterweg 2 2103 SW Heemstede the Netherlands
Department of Child Neurology Brain Center University Medical Center Utrecht the Netherlands
Department of Genetics University Medical Center Utrecht Utrecht the Netherlands
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