Recessive Loss of PI4K2A Function Causes a Developmental and Epileptic Dyskinetic Encephalopathy with Prominent Orolingual Dyskinesia.

BACKGROUND: Biallelic loss-of-function variants in PI4K2A have been associated with a neurodevelopmental disorder characterized by seizures and movement disorders, including orofacial dyskinesia. However, only 4 cases have been reported. Orolingual dyskinesia-defined as involuntary movements of the...

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Detalles Bibliográficos
Autores: Maroofian R, Ortigoza-Escobar JD, Rohilla P, Alvi JR, Mushiba AM, Almontashiri NAM, Efthymiou S, Sultan T, Balla T, Houlden H
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p29293
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29293
Access Level:acceso abierto
Palabra clave:Orolingual dyskinesia
PI4K2A
developmental and epileptic encephalopathies
genetic variants
neurodevelopmental disorders
pediatric movement disorders
Descripción
Sumario:BACKGROUND: Biallelic loss-of-function variants in PI4K2A have been associated with a neurodevelopmental disorder characterized by seizures and movement disorders, including orofacial dyskinesia. However, only 4 cases have been reported. Orolingual dyskinesia-defined as involuntary movements of the mouth and tongue-is observed in various pediatric neurodevelopmental disorders (NDD) but remains under-recognized. OBJECTIVES: The aims were to highlight orolingual dyskinesia as a core feature of PI4K2A-related disorder (PI4K2A-RD) and explore its presence across other NDDs. METHODS: We described two new families with PI4K2A-RD and reviewed the clinical features of four previously reported cases. A focused literature search was also conducted to identify other neurogenetic conditions associated with orolingual dyskinesia. RESULTS: All individuals with PI4K2A deficiency exhibited orolingual dyskinesia, along with developmental delay, movement abnormalities, and variable seizures. The literature review confirmed frequent underreporting of this feature in NDDs. CONCLUSIONS: Orolingual dyskinesia is a relevant but under-recognized clinical sign in PI4K2A-RD and other neurogenetic conditions, with potential diagnostic value. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.