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Dravet syndrome is a severe form of epilepsy characterised by recurrent seizures and cognitive impairment. It is mainly caused by variant in the SCN1A gene in 90% of cases, which codes for the α subunit of the voltage-gated sodium channel. In this study, we present one suspected case of Dravet syndrome in Moroccan child that underwent exome analysis and were confirmed by Sanger sequencing. The variant was identified in the SCN1A gene, and is a new variant that has never been described in the literature. The variant was found de nova in our case, indicating that it was not inherited from the parents. The variant, SCN1A c.965-2A>G p.(?), is located at the splice site and results in an unknown modification of the protein. This variant is considered pathogenic on the basis of previous studies. These results contribute to our knowledge of the SCN1A gene mutations associated with Dravet syndrome and underline the importance of genetic analysis in the diagnosis and confirmation of this disorder. Further studies are needed to better understand the functional consequences of this variant and its implications for therapeutic strategies in Dravet syndrome. [ABSTRACT FROM AUTHOR]

Background: Schuurs-Hoeijmakers syndrome, an autosomal dominant neurodevelopmental genetic disorder, is a rare cause of intellectual disability (ID) affecting approximately 1 to 3% of all over the world. Only 87 cases have been recorded to date, and oddly enough, the majority of them share the same mutation (c.607 C > T; p.R203W). Case presentation: This study presents the first reported case in Morocco of a 12-year-old female patient with PACS1 syndrome, identified during a cohort study of 24 patients with intellectual disability. The syndrome is caused by a de novo mutation of the PACS1 gene, located on chromosome 11, resulting in a single amino acid modification on the PACS1 protein. The abnormal protein disrupts cellular transport processes, leading to intellectual developmental delay, facial dysmorphia, and congenital anomalies. Methods and results: Exome sequencing was employed to identify the genetic mutation, and Sanger sequencing validated the presence of the recurrent mutation c.607 C > T (p.Arg203Trp) in the PACS1 gene. The mutation was found to be heterozygous and de novo, suggesting that it was not inherited from the patient's parents. Classification based on the American College of Medical Genetics and Genomics (ACMG) criteria confirmed its pathogenicity, with supporting evidence from bioinformatics analysis. The rarity of this variant in population databases further supports its pathogenic nature. Conclusion: This study expands our understanding of Schuurs-Hoeijmakers syndrome, a disorder with limited reported cases globally. The genetic heterogeneity of the disorder is highlighted, with the recurrent mutation being the most common pathogenic variant. Functional studies indicate the crucial role of PACS1 in craniofacial development and neurodevelopmental processes, with potential implications for autism spectrum disorders (ASD). Comprehensive genetic analyses are essential for accurate diagnosis and understanding the underlying causes of intellectual disabilities. Further research is warranted to unravel the mechanisms and potential therapeutic targets associated with PACS1-related neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]