Different epilepsy course of a novel AHDC1 mutation in a female monozygotic twin pair. (July 2022)

• Record Type: Journal Article
• Authors: Salvati, Andrea; Biagioni, Tommaso; Ferrari, Anna Rita; Lopergolo, Diego; Brovedani, Paola; Bartolini, Emanuele
• Is Part Of: Seizure. Volume 99(2022)
• Page Start: 127
• Page End: 130
• Publication Date: 2022-07
• Subjects: Xia-Gibbs -- Seizure -- Treatment -- Prognosis; ASM antiseizure medication -- AHDC1 AT-hook DNA binding motif containing 1 -- CGH Comparative Genomic Hybridization -- CLB Clobazam -- ETS Ethosuximide -- LCM Lacosamide -- LEV Levetiracetam -- LTG Lamotrigine -- MRI Magnetic Resonance Imaging -- NGS Next Generation Sequencing -- RUF Rufinamide -- VPA Valproic Acid -- WES whole exome sequencing; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2022.05.020
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: Xia-Gibbs syndrome shows remarkable phenotypic variability and intra-familial heterogeneity. Although seizures have frequently been reported, the clinical and EEG pattern is till undefined. Our observation suggest epilepsy may present with Lennox-Gastaut-like features. Prognosis and response to ASMs may differ even between patients with the same. mutation. Abstract: Purpose: De novo truncating mutations of AHDC1 gene cause Xia-Gibbs Syndrome (XGS), characterized by developmental delay, hypotonia, speech disturbances, sleep apnea. Seizures have been reported, yet no studies have depicted the epilepsy characteristics and outcome. Methods: We describe the clinical features of a pair of Caucasian monozygotic female twins affected by severe epilepsy and presenting the same de novo AHDC1 mutation detected by whole exome sequencing. Results: They were concordant with respect to seizure onset and type mimicking Lennox-Gastaut syndrome as well as initial EEG features, but differed in terms of epilepsy prognosis (complete seizure freedom on valproate/lamotrigine versus ongoing daily refractory seizures despite multiple drug combinations). Conclusion: Our findings suggest that patients with Xia-Gibbs Syndrome may exhibit Lennox-Gastaut-like features and that even the same AHDC1 mutation can be poorly predictive of epilepsy prognosis.