SCN1A Case Report and Literature Review - Article Example

? SCN1A case report and literature review Key words Dravet Syndrome (DS), Sodium Channel Subunit Gene (SCN1A), Severe Myoclonic Epilepsy of Infancy (SMEI), Epilepsy, Mutations, Microchromosomal, Epilepsy Limited to Females with Mental Retardation (EFMR), PCDH19 genes and Generalized Epilepsy with Febrile Seizure plus (GEFS+). Dravet Syndrome (DS) is an epileptic encephalopathy, which normally reveals its evidence mainly in human’s body after a one year gestation period (Arzimanoglou 2009). Commonly, this predicament or malady in the medical field may also be termed as Severe Myoclonic Epilepsy of Infancy (SMEI) and usually has a genetic etiology ranging between 70% and 80% patients (De Jonghe 2011), hence implying that the patients who fall in this bracket usually are the carries of Sodium Channel ?1 Subunit Gene (SCN1A) abnormalities. Truncating mutations normally account for 40% besides depicting a notable correlation with past age seizures onset (Scheffer et al. 2010). Initially, SCN1A mutations were evident in epilepsy syndrome: earlier known as Generalized Epilepsy with Febrile Seizure plus (GEFS+) (Marini, Scheffer, Nabbout, Suls, De Jonghe, Zara & Guerrini 2011, p. 24). Studies contend that patients emanating from an epileptic or febrile seizure sufferer’s family lineage in some instances confirmed to have Dravet Syndrome besides their relatives having GEFS+ phenotypes. In addition, according to Claes et al. (2001), mutational analysis on seven kids regarding SCNIA proved that all possessed de novo mutations besides depicting Dravet Syndrome fever (Marini et al. 2011, p. 24). Presently, there are over 500 mutations associated with Dravet Syndrome which distribution is along the gene and approximates a frequency of 70-80% (Marini et al. 2011). De novo mutations normally form the largest group whereas familial mutations, according to numerous studies, constitute 5–10% of the cases and are missense in nature (Marini et al. 2011, p. 23). Other categories or family members having SCNIA mutations have mild characteristic phenotypes, mainly consistent with GEFS+ distribution. An essential genetic counseling encompasses some families having more than one kid born with Dravet Syndrome. Therefore, somatic or germline mosaic mutations can adequately expound the phenomenon behind mild affected transmitting father or mother (Marini et al. 2011, p. 25). Current studies have also confirmed mosaicism presence in at least 7% of families with Dravet Syndrome besides varying mutated allele proportions in the blood, which ranges from 0.04% to 85% among 12 patients. This presents an essential factor, which expounds the intrafamilial phenotypic inconsistency across diverse ailing individuals (Arzimanoglou 2009). However, some patients depict negative DS test for SCNIA, but this does not imply they are free from the malady since they may also have SCN1A exonic deletions or chromosomal reorganizations besides adjoining genes (Marini et al. 2011, p. 25). The identification of these abnormalities is usually by Multiplex Ligation-Dependent Probe Amplification (MPLA) where additional characterization is via Comparative Genome Hybridization (CGH), which establishes the extent of inconsistencies besides examining any extra genes (Marini et al., 2011, p. 25). The small chromosomal inconsistencies that affect SCNIA – a researcher can utilize SNPs or haplotype analysis in their detection – are accountable for 2–3% among 12.5% DS negative patients. In addition, microchromosomal reorganizations extending beyond SCNIA coupled with diverse variable adjoining genes are associated by numerous studies with additional dysmorphic features. These usually depend on the genes present or extra severe epilepsy phenotype especially when more VGSC ? minor genes embed on chromosome 2q (Marini et al. 2011, p. 25). They include SCN2A, SCN3A, SCN7A, and SCN9A (Marini et al. 2011, p. 25). However, these depictions may vary across individuals, hence making them lack a concrete basis for a strong argument or predictions regarding the DS phenomenon (Singh 2009). For illustration, a study by Suls et al. (2006) concerning three patients with microchromosomal reorganizations extending beyond SCNIA showed that two among them had extra clinical features while the third one had contrary results (Dravet 2011b). Therefore, de novo mutation abnormalities have prompted clinical studies regarding family history of epilepsy, FS and familial DS cases becoming hard to reconcile (Marini et al. 2011, p. 25) since the mode of transmission or inheritance in these cases entails polygenic whereas SCNIA is among one of the genetic determinants mostly linked to DS but not with any other phenotypes (Ceulemans 2011). Researches regarding Dravet Syndrome causes among patients and numerous cases, which medical practitioners usually handle in the medical field, have reported DS cases in the absence of SCNIA involvement (Dravet 2011a). Depienne et al. (2009) contend that the causes entail involvement or the presence of PCDH19 mutations, which is evident in Epilepsy Limited to Females with Mental Retardation (EFMR) disorder (Marini et al. 2011, p. 26). Primarily, this predicament is purely an inheritance disorder where its expression varies between the two genders and assumes the forms of heterozygous females, which severely affects women but has no effect on men who only act as carriers by being heterozygous males (Scanlon & Cook 2010). To date, the function of PCDH19 gene, according to numerous biological studies, is unknown, where the medical practitioners only make postulations owing to its presence in both human and mouse’s developing brains. This has prompted biologists to claim that PCDH19 gene usually aids in establishing neural connections besides signal transduction in the synaptic membrane (Depienne et al. 2009). Numerous authors have also contended that approximately 16% or 25% of the female patients who were tested as SCNIA-negative had also PCDH19 genes instead, which, according to medical postulations, have accounted for 5% of the DS cases (Lordeon, Sitwat, Brehm & Holder 2010). Studies have also proved a predominant relationship amid SCNIA, DS and GEFS+ spectrum mainly characterized by marked phenotypic inconsistency besides the seizure onset age, seizure types, severity and unpredictable cognitive outcome (Marini et al. 2011, p. 26). Severity in this case may emanate from the SCN1A missense mutations’ location, for example, in the case of pore forming sodium channel’s region that may yield to DS while alterations linked to GEFS+ spectrum may often assume outside pore-forming location (Marini et al. 2011, p. 26). Conversely, this notion or correlation presently is not evident where numerous biologists do not observe it; owing to the core argument that both the SCNIA and GEFS+ mutations normally are selective in the way, they cause DS in humans (Guerrini, Striano, Catarino & Sisodiya 2011). Hence, implying modifier genes, genetic surroundings or their factors may have a key role in some cases besides DS in some instances assuming complex transmission through inheritance (Marini et al. 2011, p. 26). References Arzimanoglou, A 2009, ‘Dravet syndrome: from electroclinical characteristics to molecular biology,’ Epilepsia, vol. 50, suppl. 8, pp. 3–9. Ceulemans, B 2011, ‘Overall management of patients with Dravet Syndrome,’ Developmental Medicine and Child Neurology, vol. 53, suppl. 2, pp. 19–23. Claes, L, Del-Favero, J, Ceulemans, B, Lagae, L, Van Broeckhoven, C & De Jonghe, P 2001, ‘De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy,’ Am J Hum Genet, vol. 68, pp. 1327–1332. De Jonghe, P 2011, ‘Molecular genetics of Dravet Syndrome,’ Developmental Medicine and Child Neurology, vol. 53, suppl. 2, pp. 7–10. Depienne, C, Bouteiller, D, Keren, B, Cheuret, E, Poirier, K, Trouillard, O, Benyahia, B, Quelin, C, Carpentier, W, Julia, S, Afenjar, A, Gautier, A, Rivier, F, Meyer, S, Berquin, P, Helias, M, Py, I, Rivera, S, Bahi-Buisson, N & Gourfinkel-An, I 2009, ‘Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet Syndrome but mainly affects females,’ Plos Genetics, vol. 5, no. 2, pp. 1–12. Dravet, C 2011a, ‘The core Dravet Syndrome phenotype,’ Epilepsia, vol. 52, suppl. 2, pp. 3–9. Dravet, C 2011b, ‘Dravet Syndrome history,’ Developmental Medicine & Child Neurology, vol. 53, suppl. 2, pp. 1–6. Guerrini, R, Striano, P, Catarino, C & Sisodiya, S 2011, ‘Neuroimaging and neuropathology of Dravet Syndrome,’ Epilepsia, vol. 52, suppl. 2, pp. 30­–34. Lordeon, P, Sitwat, B, Brehm, D & Holder, D 2010, ‘Dravet Syndrome: a technologist’s perspective,’ American Journal of Electroneurodiagnostic Technology, vol. 50, no. 4, pp. 297–312. Marini, C, Scheffer, IE, Nabbout, R, Suls, A, De Jonghe, P, Zara, F & Guerrini, R 2011, ‘The genetics of Dravet Syndrome,’ Epilepsia, vol. 52, suppl. 2, pp. 24–29, doi: 10.1111/j.1528-1167.2011.02997.x. Scanlon, A & Cook, S 2010, ‘Febrile seizures, genetic (generalized) epilepsy with febrile seizures plus, and Dravet Syndrome,’ Journal for Specialists in Pediatric Nursing, vol. 15, no. 2, pp. 154–159. Scheffer, I, Yue-Hua, Z, Gecz, J & Dibbens, L 2010, ‘Genetics of the epilepsies: genetic twists in the channels and other tales,’ Epilepsia (Series 4), vol. 51, pp. 33–36. Singh, N, Pappas, C, Dahle, E, Claes, L, Pruess, T, De Jonghe, P, Thompson, J, Dixon, M, Gurnett, C, Peiffer, A, White, H, Filloux, F & Leppert, M 2009, ‘A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet Syndrome,’ Plos Genetics, vol. 5, no. 9, pp. 1–12. Read More