Teplyshova Anna, Sharkov Artem
Research Center of Neurology, Moscow, Russia.
Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University, Moscow, Russia.
Front Genet. 2024 Oct 23;15:1477466. doi: 10.3389/fgene.2024.1477466. eCollection 2024.
WWOX developmental and epileptic encephalopathy is characterised by drug-resistant epilepsy with onset within the first year of life and severe psychomotor developmental delay. This report presents for the first time a clinical case of an adult patient with a homozygous likely pathogenic variant (p.Thr12Met) in the gene, with more than 40 years of follow-up. The patient had refractory epilepsy with various types of seizures during his life: mainly epileptic spasms, autonomic, myoclonic, tonic seizures, and absences. The patient had a prominent developmental delay with a lack of expressive speech, but by the age of 3, he had acquired the skills to sit, crawl, and walk with support. In adolescence, there was an acute regression of acquired skills to a total absence of independent motor activity. The patient had dysmorphic features, such as upslanting palpebral fissures, arched eyebrows, and hypertelorism. For many years, the patient was given a diagnosis of cerebral palsy; 38 years after the onset of the disease, he was given a molecular genetic diagnosis of -associated developmental and epileptic encephalopathy. Our observation illustrates the natural history of -DEE and the high clinical significance of early genetic diagnostics for identifying the cause of developmental delay and resistant epilepsy.
WWOX相关的发育性和癫痫性脑病的特征为出生后第一年内发病的耐药性癫痫和严重的精神运动发育迟缓。本报告首次呈现了一名成年患者的临床病例，该患者基因存在纯合的可能致病性变异（p.Thr12Met），并进行了40多年的随访。患者一生中患有难治性癫痫，发作类型多样：主要为癫痫性痉挛、自主性发作、肌阵挛发作、强直发作和失神发作。患者存在明显的发育迟缓，缺乏表达性语言，但到3岁时，他已获得在支撑下坐、爬和行走的能力。在青春期，已获得的技能急剧退化，完全丧失独立运动能力。患者具有畸形特征，如睑裂上斜、眉弓高拱和眼距增宽。多年来，患者被诊断为脑瘫；疾病发作38年后，他被给予与WWOX相关的发育性和癫痫性脑病的分子遗传学诊断。我们的观察说明了WWOX相关的发育性和癫痫性脑病的自然病史，以及早期基因诊断对于确定发育迟缓及耐药性癫痫病因的高度临床意义。
