Dravet syndrome and Dravet-like phenotype: a systematic review of the SCN1A and PCDH19 variants

Background: Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with a prevalence around 1/40,000 people worldwide. Approximately 80% of patients with DS present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage- dependent sodium channel. SCN1A variants were also related to DS. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. Objectives: To clarify the differences between DS and DS-like phenotype according to the SCN1A and PCDH19 variants. Methodology: A review from March/2019 to November/2020 was conducted in PubMed and VHL databases, following PRISMA criteria. Results: 19 studies were included and a significant proportion of patients with DS carrying SCN1A was greater than patients with DS-like phenotype harboring PCDH19 variants (76.6% vs. 23.4%). Considering SCN1A and PCDH19, 47 variants were pathogenic and 12 of uncertain significance; 25% were deletions and 75% were single- nucleotide variants. Autism was predominantly observed in patients with DS-like carrying PCDH19 variants compared to SCN1A variants carriers (62.5% vs. 37.5%, p=0.044). In addition, it was noticed a significant predisposition to hyperthermia during seizures in patients with variants in the PCDH19 (p=0.003). There was no significance differences between both groups and cognitive deficit, ataxia, behavior problems, and motor deficit. Conclusions: The study is the first to point out differences between the DS and DS-like phenotype according to the SCN1A and PCDH19 variants.