Dravet Syndrome (DS) is a developmental epileptic encephalopathy characterized by drug-resistant seizures and other clinical features, including intellectual disability and behavioral, sleep, and gait problems. The pathogenesis is strongly connected to voltage-gated sodium channel dysfunction. The current consensus of seizure management in DS consists of a combination of conventional and recently approved drugs such as stiripentol, cannabidiol, and fenfluramine. Despite promising results in randomized clinical trials and extension studies, the prognosis of the developmental outcomes of patients with DS remains unfavorable. The article summarizes recent changes in the therapeutic approach to DS and discusses ongoing clinical research directions. Serotonergic agents under investigation show promising results and may replace less DS-specific medicines. The use of antisense nucleotides and gene therapy is focused not only on symptom relief but primarily addresses the underlying cause of the syndrome. Novel compounds, after expected safe and successful implementation in clinical practice, will open a new era for patients with DS. The main goal of causative treatment is to modify the natural course of the disease and provide the best neurodevelopmental outcome with minimum neurological deficit.

Pathogenic variants in the PAK1 gene are linked to neurodevelopmental and neurodegenerative disorders by disrupting neuronal signaling and function. Despite increasing recognition, the mechanisms underlying these conditions remain incompletely understood, limiting therapeutic options. Here, we report a novel de novo PAK1 variant, c.396C>A (p.Asn132Lys), in a 5-year-old girl with Intellectual Developmental Disorder with Macrocephaly, Seizures, and Speech Delay (IDDMSSD). The patient presented with mild intellectual disability, delayed speech, macrocephaly, hypotonia, gait ataxia, autism-like behaviors, and focal epileptiform activity. Trio exome sequencing confirmed the variant as likely pathogenic, absent in her parents and population databases. This finding expands the phenotypic spectrum of PAK1-related disorders and underscores the critical role of the autoinhibitory domain in neurodevelopment. In addition, we performed a comprehensive literature review of PAK1 variants affecting both the autoregulatory and kinase domains, summarizing associated clinical features and pathogenic mechanisms. Our study highlights the importance of identifying PAK1 pathogenic variants for accurate diagnosis, refined genotype-phenotype correlations, and the development of potential targeted therapeutic strategies. By integrating novel case data with existing literature, this work advances understanding of PAK1-related neurodevelopmental disorders and supports the application of genetic analysis in rare pediatric NDD cases.