Confirming an expanded spectrum of <i>SCN2A</i> mutations: a case series

Matalon, Dena; Goldberg, Ethan M.; Medne, Līvija; Marsh, Eric D.

doi:10.1684/epd.2014.0641

Cited by 33 publications

(29 citation statements)

References 22 publications

(27 reference statements)

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“…The clinical characteristics of these patients in comparison to other SCN2A-associated syndromes are that seizures recurred more frequently and persisted longer than in typical BFNIS and that those were more difficult to treat [24]. In contrast to more severe epileptic encephalopathies [9][10][11][12][13][14][15], the seizures still remitted after 5-13 months (except for few occasional later seizures in patient #4). Since drugs have been discontinued in patient #2, seizure freedom can be attributed to spontaneous remission, whereas this remains unclear in the other cases, as treatment has been continued (patients #1 and #3) or restarted after seizure relapse during a drug-free period (patient #4).…”

Section: Discussionmentioning

confidence: 99%

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Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia

et al. 2015

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Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by -4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na(+) current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia.

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Section: Discussionmentioning

confidence: 99%

“…These mutations mainly lead to gain-of-function defects causing neuronal hyperexcitability [8,7]. More severe, non-familial phenotypes with neonatal onset seizures caused by de novo SCN2A mutations are increasingly described [9][10][11][12][13][14]. One loss-of-function mutation causes epileptic encephalopathy with later onset [15].…”

Section: Introductionmentioning

confidence: 99%

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia

et al. 2015

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“…One of our patients, DB13-002, was found to have a KCNT1 mutation. DB12-014 was found to have a mutation in SCN2A , which is a known sodium channel gene implicated in infant onset epilepsy (Baasch et al, 2014; Matalon et al, 2014; Hackenburg et al, 2014), including infantile spasms (Sundaram et al, 2013) and Ohtahara syndrome (Nakamura et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Characteristic Features of the Interictal EEG Background in 2 Patients With Malignant Migrating Partial Epilepsy in Infancy

Selioutski

Seltzer

Burchfiel

et al. 2015

Journal of Clinical Neurophysiology

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Purpose To describe chronological electrographic features of the interictal EEG background observed in two patients with MMPEI from neonatal to early infantile period. Methods EEGs of two patients who fulfilled diagnostic criteria for MMPEI were acquired over the period of 6 months to monitor treatment efficacy and characterize seizures and other paroxysmal events. Results Both patients followed a similar sequential pattern. A distinctive evolution from a dysmature term neonatal EEG pattern to an asynchronous suppression burst pattern was observed prior to the interictal background becoming continuous. Conclusions Physicians providing care to infants with intractable epilepsy and burst suppression EEG pattern should be alert to the possibility of MMPEI. An earlier diagnosis of MMPEI would help guide diagnostic workup including genetic testing.

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“…Approximately two‐thirds of children with DEE have epilepsy onset within the first 3 months of life, mostly during the neonatal period …”

Section: The Spectrum Of Scn2a‐related Disordersmentioning

confidence: 99%

Phenotypic spectrum and genetics of SCN2A‐related disorders, treatment options, and outcomes in epilepsy and beyond

Wolff¹,

Brunklaus

Zuberi

2019

Epilepsia

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Pathogenic variants in the SCN2A gene are associated with a variety of neurodevelopmental phenotypes, defined in recent years through multicenter collaboration.Phenotypes include benign (self-limited) neonatal and infantile epilepsy and more severe developmental and epileptic encephalopathies also presenting in early infancy. There is increasing evidence that an important phenotype linked to the gene is autism and intellectual disability without epilepsy or with rare seizures in later childhood. Other associations of SCN2A include the movement disorders chorea and episodic ataxia. It is likely that as genetic testing enters mainstream practice that new phenotypic associations will be identified. Some missense, gain of function variants tend to present in early infancy with epilepsy, whereas other missense or truncating, loss of function variants present with later-onset epilepsies or intellectual disability only. Knowledge of both mutation type and functional consequences can guide precision therapy. Sodium channel blockers may be effective antiepileptic medications in gain of function, neonatal and infantile presentations.

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Confirming an expanded spectrum of SCN2A mutations: a case series

Cited by 33 publications

References 22 publications

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia

Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia

Characteristic Features of the Interictal EEG Background in 2 Patients With Malignant Migrating Partial Epilepsy in Infancy

Phenotypic spectrum and genetics of SCN2A‐related disorders, treatment options, and outcomes in epilepsy and beyond

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