Dataset Information

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

ABSTRACT: SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

SUBMITTER: Ribeiro-Constante J

PROVIDER: S-EPMC10948473 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Developmental outcome of electroencephalographic findings in <i>SYNGAP1</i> encephalopathy.

Ribeiro-Constante Juliana J Tristán-Noguero Alba A Martínez Calvo Fernando Francisco FF Ibañez-Mico Salvador S Peña Segura José Luis JL Ramos-Fernández José Miguel JM Moyano Chicano María Del Carmen MDC Camino León Rafael R Soto Insuga Víctor V González Alguacil Elena E Valera Dávila Carlos C Fernández-Jaén Alberto A Plans Laura L Camacho Ana A Visa-Reñé Nuria N Martin-Tamayo Blázquez María Del Pilar MDP Paredes-Carmona Fernando F Marti-Carrera Itxaso I Hernández-Fabián Aránzazu A Tomas Davi Meritxell M Sanchez Merce Casadesus MC Herraiz Laura Cuesta LC Pita Patricia Fuentes PF Gonzalez Teresa Bermejo TB O'Callaghan Mar M Iglesias Santa Polonia Federico Felipe FF Cazorla María Rosario MR Ferrando Lucas María Teresa MT González-Meneses Antonio A Sala-Coromina Júlia J Macaya Alfons A Lasa-Aranzasti Amaia A Cueto-González Anna Ma AM Valera Párraga Francisca F Campistol Plana Jaume J Serrano Mercedes M Alonso Xenia X Del Castillo-Berges Diego D Schwartz-Palleja Marc M Illescas Sofía S Ramírez Camacho Alia A Sans Capdevila Oscar O García-Cazorla Angeles A Bayés Àlex À Alonso-Colmenero Itziar I

Frontiers in cell and developmental biology 20240305

<i>SYNGAP1</i> haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. ...[more]

PMID: 38505260

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Project description:Objective: We aimed to explore the associated clinical phenotype and the natural history of patients with SYNGAP1 gene variations during early childhood and to identify their genotype-phenotype correlations. Methods: This study used a cohort of 13 patients with epilepsy and developmental disorder due to SYNGAP1 mutations, namely, 7 patients from Shenzhen Children's Hospital between September 2014 and January 2020 and 6 patients from previously published studies. Their clinical data were studied. Results: A total of 13 children with SYNGAP1 gene variants (eight boys and five girls) were identified. The age of disease onset was in infancy. Mutations were located between exons 8 and 15; most were frameshift or truncated mutations. Four mutation sites (c.924G > A, c.1532-2_1532del, c.1747_1755dup, and c.1735_1738del) had not been reported before. All patients had global developmental delay within the first year of life, and intellectual impairment became gradually apparent. Some of them developed behavioral problems. The developmental delay occurred before the onset of seizures. All seven patients in our cohort presented with epilepsy; myoclonic seizures, absence seizures, and epileptic spasms were the most common seizure types. Abnormal electroencephalograms were identified from five patients before the onset of their seizures. All patients suffered from drug-resistance seizures. However, comorbidities such as behavioral problems were less frequently observed. Conclusion: The most common age of disease onset in SYNGAP1 gene mutations is in infancy, while neurodevelopmental delay and epilepsy are the major phenotypes. They have a higher percentage of drug-resistant epilepsy and epileptic spasms than those in previous reports. We should give attention to the patients with abnormal EEGs without seizures and think about the suitable time of the anti-seizure medications for them. We have not found the genotype-phenotype correlation. Trial registration: Chinese Clinical Trial Registry, Registration number: ChiCTR2100049289 (https://www.chictr.org.cn/listbycreater.aspx).

Dataset Information

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

Publications

Developmental outcome of electroencephalographic findings in <i>SYNGAP1</i> encephalopathy.

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