Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov:53:63-72.
doi: 10.1016/j.ejpn.2024.10.005. Epub 2024 Oct 9.

Developmental and epileptic encephalopathy 56 due to YWHAG variants: 12 new cases and review of the literature

Maria Eugenia Amato  1 , Sol Balsells  2 , Loreto Martorell  3 , Adrián Alcalá San Martín  4 , Karen Ansell  5 , Malene Landbo Børresen  6 , Heather Johnson  7 , Christian Korff  8 , Stephanie Garcia-Tarodo  8 , Jeremie Lefranc  9 , Anne-Sophie Denommé-Pichon  10 , Elisabeth Sarrazin  11 , Nora Zsuzsanna Szabo  12 , Jorge M Saraiva  13 , Dorota Wicher  14 , Anne Goverde  15 , Karen G C B Bindels-de Heus  16 , Tahsin Stefan Barakat  17 , Juan Darío Ortigoza-Escobar  18
Affiliations

Developmental and epileptic encephalopathy 56 due to YWHAG variants: 12 new cases and review of the literature

Maria Eugenia Amato et al. Eur J Paediatr Neurol. 2024 Nov.

Abstract

Background and objectives: Developmental and epileptic encephalopathy 56 (DEE-56) is caused by pathogenic variants in YWHAG and is characterized by early-onset epilepsy and neurodevelopmental delay. This study reports on a cohort of DEE-56 individuals, correlating antiseizure medication usage and comorbidities, to aid in understanding disease evolution.

Methods: We analyzed data from thirty-nine individuals aged 3-40 years with YWHAG variants, including 12 previously unreported individuals (2 of these with recurrent distal 7q11.23 deletions) and 27 previously published cases (21 families, including 3 adult individuals reported in a family case). Our assessments encompassed clinical, radiological, and genetic evaluations. All procedures adhered to standardized protocols for patient approvals, registrations, and data collection.

Results: Individuals with YWHAG variants exhibited variable psychomotor delay, with the majority experiencing mild intellectual disability. Early-onset seizures, particularly febrile seizures, were common, with various seizure types reported. Valproic acid has emerged as an effective antiseizure medication. Movement disorders were present in a subset of individuals, primarily manifesting as ataxia and tremor. Comorbidities such as autism spectrum disorders and attention deficit-hyperreactivity disorder were observed in a proportion of individuals. We identified a novel YWHAG variant (c.634_645del/p.Asn212_Ser215del) and expanded the genotypic spectrum of the disease.

Conclusions: We provide insights into the clinical, radiological, and genetic features of YWHAG-related epileptic encephalopathy. Despite mild clinical symptoms, affected individuals face challenges in daily functioning, underscoring the need for comprehensive care. Valproic acid has been used for seizure control with variable results.

Keywords: Ataxia; Epilepsy; Febrile seizures; Intellectual disability; YWHAG.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest None of the authors has any conflict of interest to disclose.