Di Muro Ester, Palumbo Pietro, Carella Massimo, Benvenuto Mario, Bianchi Maria Rachele, Costantino Umberto, Di Maggio Giovanni, Castori Marco, d'Orsi Giuseppe, Palumbo Orazio
UOC Genetica Medica, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, FG, Italy.
Epilepsy Center-Neurological Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, 71013 San Giovanni Rotondo, FG, Italy.
Genes (Basel). 2025 Mar 10;16(3):323. doi: 10.3390/genes16030323.
The gene and its product protein have been linked to a wide spectrum of neurodevelopmental disorders named -related disorders. Clinical presentation is highly variable and characteristically includes acquired cognitive, behavioral, and language impairment, as well as epilepsy, ranging from benign forms to severe epileptic encephalopathy. Recent genetic investigations have expanded the clinical spectrum of heterozygous variants, improving our understanding of genotype-phenotype correlations. However, there have been few long-term observational studies of patients affected by the genetically determined -related disease. To understand the long-term changes in clinical features, we described three patients from two Italian families, carrying variants in the gene. After more than a decade of extensive electro-clinical follow-up, we observed a progressive cognitive decline associated with severe behavioral disturbances, despite clinical seizure control. The persistent presence of EEG epileptiform abnormalities over time suggests the need for a longitudinal neurophysiological study to monitor disease progression and evaluate the potential for anti-seizure medication discontinuation. Our study offers new insights into the natural progression of epilepsy in -related disorders, highlighting that a more detailed understanding of the phenotype and timely, personalized treatment could enhance the management and quality of life for both patients and their caregivers.
该基因及其产物蛋白与一系列名为“-相关疾病”的神经发育障碍有关。临床表现高度可变，典型症状包括后天获得性认知、行为和语言障碍，以及癫痫，从良性形式到严重癫痫性脑病不等。最近的基因研究扩展了杂合变异的临床谱，增进了我们对基因型-表型相关性的理解。然而，对于受基因决定的“-相关疾病”影响的患者，长期观察性研究很少。为了解临床特征的长期变化，我们描述了来自两个意大利家庭的三名携带该基因变异的患者。经过十多年广泛的电临床随访，我们观察到尽管临床癫痫得到控制，但仍出现与严重行为障碍相关的进行性认知衰退。随着时间推移，脑电图癫痫样异常持续存在，这表明需要进行纵向神经生理学研究，以监测疾病进展并评估停用抗癫痫药物的可能性。我们的研究为“-相关疾病”中癫痫的自然进展提供了新见解，强调对表型的更详细理解以及及时、个性化的治疗可以改善患者及其照顾者的管理和生活质量。
