Recessive Loss of PI4K2A Function Causes a Developmental and Epileptic Dyskinetic Encephalopathy with Prominent Orolingual Dyskinesia.
Por:
Maroofian R, Ortigoza-Escobar JD, Rohilla P, Alvi JR, Mushiba AM, Almontashiri NAM, Efthymiou S, Sultan T, Balla T and Houlden H
Publicada:
1 oct 2025
Ahead of Print:
7 ago 2025
Resumen:
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.
Filiaciones:
Maroofian R:
Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, United Kingdom
Ortigoza-Escobar JD:
Movement Disorders Unit, Pediatric Neurology Department, Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
U-703 Centre for Biomedical Research On Rare Diseases (CIBER-ER) Instituto de Salud Carlos III, Barcelona, Spain
European Reference Network for Rare Neurological Diseases (ERN-RND), Barcelona, Spain
Rohilla P:
Section on Molecular Signal Transduction, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Alvi JR:
Department of Pediatric Neurology, Institute of Child Health, Children Hospital Lahore, Lahore, Pakistan
Mushiba AM:
Clinical Genetic Section, Pediatric Subspecialties Department, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
Almontashiri NAM:
Center for Genetics and Inherited Diseases and Clinical Laboratory Sciences, Taibah University, Madinah, Saudi Arabia
Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
Efthymiou S:
Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, United Kingdom
Sultan T:
Department of Pediatric Neurology, Institute of Child Health, Children Hospital Lahore, Lahore, Pakistan
Balla T:
Section on Molecular Signal Transduction, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Houlden H:
Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, United Kingdom
Green Submitted, hybrid
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