FHF1 (FGF12) epileptic encephalopathy

Al-Mehmadi, Sameer; Splitt, Miranda; Ramesh, Venkateswaran; DeBrosse, Suzanne D.; Dessoffy, Kimberly; Xia, Fan; Yang, Yaping; Rosenfeld, Jill A.; Cossette, Patrick; Michaud, Jacques L.; Hamdan, Fadi F.; Campeau, Philippe M.; Minassian, Berge A.

doi:10.1212/nxg.0000000000000115

Cited by 36 publications

(35 citation statements)

References 4 publications

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“…It is possible that the CNV has gain-of-function effects, similar to the previous patients. Similar to our patient, phenytoin was used also in most of the previous patients with the R52H mutation in FGF12 , 6 suggesting that the same mechanism underlies the pathogenicity of the previous cases and our case. The aberrant proteins from the duplicated allele in our patient are predicted to have duplicated sodium channel–binding sites.…”

supporting

confidence: 81%

Phenytoin-responsive epileptic encephalopathy with a tandem duplication involving FGF12

et al. 2017

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supporting

confidence: 81%

Phenytoin-responsive epileptic encephalopathy with a tandem duplication involving FGF12

et al. 2017

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“…Review 179 described in association with a distinct epilepsy-dyskinesia phenotype, more severe than Dravet syndrome, with a prominent hyperkinetic movement disorder. [39][40][41] Potassium channel genes Autosomal dominant mutations in KCNT1, which encodes the sodium-activated potassium channel, are identified in a wide range of epileptic disorders from benign familial neonatal-infantile seizures and autosomal dominant nocturnal frontal lobe epilepsy to severe DEE syndromes, such as Ohtahara syndrome, West syndrome, and EIMFS. Mutations in FHF1 (R52H), have been reported in patients with early onset epilepsy associated with progressive cerebellar atrophy and ataxia.…”

Section: Sodium Channel Genesmentioning

confidence: 99%

The expanding spectrum of movement disorders in genetic epilepsies

Papandreou

Danti

Spaull

et al. 2019

Develop Med Child Neuro

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An ever‐increasing number of neurogenetic conditions presenting with both epilepsy and atypical movements are now recognized. These disorders within the ‘genetic epilepsy‐dyskinesia’ spectrum are clinically and genetically heterogeneous. Increased clinical awareness is therefore necessary for a rational diagnostic approach. Furthermore, careful interpretation of genetic results is key to establishing the correct diagnosis and initiating disease‐specific management strategies in a timely fashion. In this review we describe the spectrum of movement disorders associated with genetically determined epilepsies. We also propose diagnostic strategies and putative pathogenic mechanisms causing these complex syndromes associated with both seizures and atypical motor control. What this paper adds Implicated genes encode proteins with very diverse functions. Pathophysiological mechanisms by which epilepsy and movement disorder phenotypes manifest are often not clear. Early diagnosis of treatable disorders is essential and next generation sequencing may be required.

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“…6 The identification of a recurrent de novo mutation in 6 unrelated patients all presenting with early-onset epilepsy strongly supports the involvement of FGF12 in disease pathogenesis. 7,8 Moreover, the identification of additional patients carrying the same FGF12 variant broadens the phenotypic spectrum associated with this gene.…”

Section: Discussionmentioning

confidence: 72%

De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy

et al. 2016

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Objective:We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation.Methods:Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report.Results:We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction.Conclusions:The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report.

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FHF1 (FGF12) epileptic encephalopathy

Cited by 36 publications

References 4 publications

Phenytoin-responsive epileptic encephalopathy with a tandem duplication involving FGF12

Phenytoin-responsive epileptic encephalopathy with a tandem duplication involving FGF12

The expanding spectrum of movement disorders in genetic epilepsies

De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy

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