GATOR1-related focal cortical dysplasia in epilepsy surgery patients and their families: A possible gradient in severity?
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu kazuistiky, časopisecké články
PubMed
33461085
DOI
10.1016/j.ejpn.2020.12.001
PII: S1090-3798(20)30222-1
Knihovny.cz E-zdroje
- Klíčová slova
- Epilepsy surgery, Focal cortical dysplasia, Focal epilepsy, GATOR1, Malformations of cortical development, Targeted gene panel sequencing,
- MeSH
- dítě MeSH
- fenotyp MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- malformace mozkové kůry genetika chirurgie MeSH
- mladiství MeSH
- nádorové supresorové proteiny genetika MeSH
- proteiny aktivující GTPasu genetika MeSH
- refrakterní epilepsie genetika MeSH
- retrospektivní studie MeSH
- zárodečné mutace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- DEPDC5 protein, human MeSH Prohlížeč
- nádorové supresorové proteiny MeSH
- NPRL2 protein, human MeSH Prohlížeč
- NPRL3 protein, human MeSH Prohlížeč
- proteiny aktivující GTPasu 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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