Apparently certain confusion is currently dominating the classification of the genetics of Dravet syndrome. According to different databases, the disorder can be caused by SCN1A mutation only, by SCN1A and GABGR2 mutation or by SCN1A, GABRG2 and SCN2A mutation. So, let’s try to make the story simple.
Dravet syndrome, first described by Dravet in 1978, is an early-onset epileptic encephalopathy characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever. Onset is in the first year of life. The disease course is also characterized by delay in psychomotor development, behavioral disorders and ataxia. Dravet syndrome was previously known also as severe myoclonic epilepsy of infancy (SMEI).
According to the OMIM database, Dravet syndrome can be caused by heterozygous mutation in the SCN1A gene on chromosome 2q24 (of note, mutations in this gene are also causing autosomal dominant generalized epilepsy with febrile seizures plus - GEFSP2).
The SCN9A gene is sometimes considered as another gene causing Dravet syndrome, although it has been proposed that mutations in this gene are actually just modifying factors. The question appears not be that clear, since both patients with double heterozygous mutation in SCN1A and SCN9A and patients with SCN9A mutations only have been reported.
According to Genereviews, Dravet syndrome can be also caused by GABRG2 mutations, which according to the OMIM database are actually causing GEFSP3.
SCN2A mutations can also cause a phenotype with severe myoclonic epilepsy, ataxia, and pain (called early infantile epileptic encephalopathy - EIEE11). In suggestive phenotypes, mutations in SCN1A are more frequently identified than mutations in SCN2A by a ratio of about 9:1.
The differential diagnosis of Dravet syndrome can include: pyridoxine-dependent seizures and B6-related epilepsies, inborn errors of metabolism, including mitochondrial dysfunction, biotinidase deficiency, glucose transporter type 1 deficiency, and hepatic porphyrias. If the family history is positive for other individuals with epilepsy, the differential diagnosis may include disorders relating to mutations in the following genes: SCN9A (FEB3B, OMIM 603415), GPR98 (FEB4, OMIM 602851), SCN1B (GEFSP1, OMIM 600235), and GABRD (GEFSP5, OMIM 613060). Also mutations in PCDH19, the gene encoding protocadherin, can cause a Dravet syndrome phenotype in the context of X-linked inheritance with most females being symptomatic (Miller IO et al, 2011).
Dravet syndrome, first described by Dravet in 1978, is an early-onset epileptic encephalopathy characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever. Onset is in the first year of life. The disease course is also characterized by delay in psychomotor development, behavioral disorders and ataxia. Dravet syndrome was previously known also as severe myoclonic epilepsy of infancy (SMEI).
According to the OMIM database, Dravet syndrome can be caused by heterozygous mutation in the SCN1A gene on chromosome 2q24 (of note, mutations in this gene are also causing autosomal dominant generalized epilepsy with febrile seizures plus - GEFSP2).
The SCN9A gene is sometimes considered as another gene causing Dravet syndrome, although it has been proposed that mutations in this gene are actually just modifying factors. The question appears not be that clear, since both patients with double heterozygous mutation in SCN1A and SCN9A and patients with SCN9A mutations only have been reported.
According to Genereviews, Dravet syndrome can be also caused by GABRG2 mutations, which according to the OMIM database are actually causing GEFSP3.
SCN2A mutations can also cause a phenotype with severe myoclonic epilepsy, ataxia, and pain (called early infantile epileptic encephalopathy - EIEE11). In suggestive phenotypes, mutations in SCN1A are more frequently identified than mutations in SCN2A by a ratio of about 9:1.
The differential diagnosis of Dravet syndrome can include: pyridoxine-dependent seizures and B6-related epilepsies, inborn errors of metabolism, including mitochondrial dysfunction, biotinidase deficiency, glucose transporter type 1 deficiency, and hepatic porphyrias. If the family history is positive for other individuals with epilepsy, the differential diagnosis may include disorders relating to mutations in the following genes: SCN9A (FEB3B, OMIM 603415), GPR98 (FEB4, OMIM 602851), SCN1B (GEFSP1, OMIM 600235), and GABRD (GEFSP5, OMIM 613060). Also mutations in PCDH19, the gene encoding protocadherin, can cause a Dravet syndrome phenotype in the context of X-linked inheritance with most females being symptomatic (Miller IO et al, 2011).
References: see text.
