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

Rampazzo, Ana Carla Mondek; Santos, Rafael Rodrigues Pinheiro dos; Maluf, Fernando Arfux; Simm, Renata; Marson, Fernando Augusto Lima; Ortega, Manoela Marques; Aguiar, Paulo Henrique Pires de

doi:10.1007/s10048-021-00644-7

Cited by 12 publications

(18 citation statements)

References 26 publications

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“…In a recent study, mutations in the PCDH19 gene appear to be the underlying cause of DS-like phenotype in 16% of DS negative for SCN1A mutations (54). The variants in the SCN1A and PCDH19 genes show some similarities that link DS to DS-like, but they differ from each other for some peculiarities (55). Due to the unusual X-linked inheritance of PCDH19 gene mutations, DS-like is more common in females.…”

Section: Dravet-like Syndromementioning

confidence: 99%

“…The onset of symptoms is earlier in DS than in DS-like, with an average range of 3–6 and 8–54 months, respectively ( 56 , 57 ). Fever represents the main triggering seizure factor for both DS and DS-like, however PCDH19 mutations show fewer provocation factors for seizure initiation ( 55 ). Clonic and hemiclonic seizures are mainly related to SCN1A mutations that also present a higher prevalence of generalized tonic-clonic seizures and atypical absences with more common status epilepticus.…”

Section: Dravet-like Syndromementioning

confidence: 99%

“…DS-like phenotype carrying the PCDH19 pathogenic variants has greater variability in cognitive disability including some cases without intellectual impairment ( 20 , 22 , 57 ). In contrast, patients with DS present a greater degree of cognitive impairment, regardless of variant significance ( 55 ). Autism predominantly involves DS-like, occurring in 62.5% of patients with PCDH19 mutations vs. 37.5% of patients with SCN1A mutations ( 55 ).…”

Section: Dravet-like Syndromementioning

confidence: 99%

“…In contrast, patients with DS present a greater degree of cognitive impairment, regardless of variant significance ( 55 ). Autism predominantly involves DS-like, occurring in 62.5% of patients with PCDH19 mutations vs. 37.5% of patients with SCN1A mutations ( 55 ).…”

Section: Dravet-like Syndromementioning

confidence: 99%

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The Broad Clinical Spectrum of Epilepsies Associated With Protocadherin 19 Gene Mutation

et al. 2022

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Protocadherin 19 (PCDH19) gene is one of the most common genes involved in epilepsy syndromes. According to literature data PCDH19 is among the 6 genes most involved in genetic epilepsies. PCDH19 is located on chromosome Xq22.1 and is involved in neuronal connections and signal transduction. The most frequent clinical expression of PCDH19 mutation is epilepsy and mental retardation limited to female (EFMR) characterized by epileptic and non-epileptic symptoms affecting mainly females. However, the phenotypic spectrum of these mutations is considerably variable from genetic epilepsy with febrile seizure plus to epileptic encephalopathies. The peculiar exclusive involvement of females seems to be caused by a cellular interference in heterozygosity, however, affected mosaic-males have been reported. Seizure types range from focal seizure to generalized tonic-clonic, tonic, atonic, absences, and myoclonic jerks. Treatment of PCDH19-related epilepsy is limited by drug resistance and by the absence of specific treatment indications. However, seizures become less severe with adolescence and some patients may even become seizure-free. Non-epileptic symptoms represent the main disabilities of adult patients with PCDH19 mutation. This review aims to analyze the highly variable phenotypic expression of PCDH19 gene mutation associated with epilepsy.

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Section: Dravet-like Syndromementioning

confidence: 99%

Section: Dravet-like Syndromementioning

confidence: 99%

Section: Dravet-like Syndromementioning

confidence: 99%

Section: Dravet-like Syndromementioning

confidence: 99%

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The Broad Clinical Spectrum of Epilepsies Associated With Protocadherin 19 Gene Mutation

et al. 2022

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“…PCDH19 , located on chromosome XQ22.1, encodes the protocadherin-19 and is the second-most pathogenic gene of DS, accounting for 23.4% of patients with SCN1A -negative DS ( 61 ). The product of PCDH19 is protocadherin-19, a single-channel transmembrane glycoprotein, which is the largest subgroup of the cadherin superfamily, and plays an important role in cell adhesion, dendritic self-avoidance, and axon guidance.…”

Section: Discussion and Synthesismentioning

confidence: 99%

Do All Roads Lead to Rome? Genes Causing Dravet Syndrome and Dravet Syndrome-Like Phenotypes

et al. 2022

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BackgroundDravet syndrome (DS) is a severe epileptic encephalopathy mainly caused by haploinsufficiency of the gene SCN1A, which encodes the voltage-gated sodium channel NaV1. 1 in the brain. While SCN1A mutations are known to be the primary cause of DS, other genes that may cause DS are poorly understood. Several genes with pathogenic mutations result in DS or DS-like phenotypes, which may require different drug treatment approaches. Therefore, it is urgent for clinicians, especially epilepsy specialists to fully understand these genes involved in DS in addition to SCN1A. Particularly for healthcare providers, a deep understanding of these pathogenic genes is useful in properly selecting and adjusting drugs in a more effective and timely manner.ObjectiveThe purpose of this study was to identify genes other than SCN1A that may also cause DS or DS-like phenotypes.MethodsA comprehensive search of relevant Dravet syndrome and severe myoclonic epilepsy in infancy was performed in PubMed, until December 1, 2021. Two independent authors performed the screening for potentially eligible studies. Disagreements were decided by a third, more professional researcher or by all three. The results reported by each study were narratively summarized.ResultsA PubMed search yielded 5,064 items, and other sources search 12 records. A total of 29 studies published between 2009 and 2021 met the inclusion criteria. Regarding the included articles, seven studies on PCDH19, three on SCN2A, two on SCN8A, five on SCN1B, two on GABRA1, three on GABRB3, three on GABRG2, and three on STXBP1 were included. Only one study was recorded for CHD2, CPLX1, HCN1 and KCNA2, respectively. It is worth noting that a few articles reported on more than one epilepsy gene.ConclusionDS is not only identified in variants of SCN1A, but other genes such as PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, STXBP1 can also be involved in DS or DS-like phenotypes. As genetic testing becomes more widely available, more genes associated with DS and DS-like phenotypes may be identified and gene-based diagnosis of subtypes of phenotypes in this spectrum may improve the management of these diseases in the future.

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Identification of novel and de novo variant in the SCN1A gene confirms Dravet syndrome in Moroccan child: a case report

El Mouhi,

Amllal,

Abbassi

et al. 2024

Mol Biol Rep

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

Cited by 12 publications

References 26 publications

The Broad Clinical Spectrum of Epilepsies Associated With Protocadherin 19 Gene Mutation

The Broad Clinical Spectrum of Epilepsies Associated With Protocadherin 19 Gene Mutation

Do All Roads Lead to Rome? Genes Causing Dravet Syndrome and Dravet Syndrome-Like Phenotypes

Identification of novel and de novo variant in the SCN1A gene confirms Dravet syndrome in Moroccan child: a case report

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