Episodic ataxia type 2 manifests as epileptiform electroencephalographic activity with no epileptic attacks in two family members

Kaido, Misako; Furuta, Mitsuru; Nakamori, Mikihito; Yuasa, Yoshihito; Takahashi, Masanori

doi:10.5692/clinicalneurol.cn-000854

Cited by 9 publications

(11 citation statements)

References 8 publications

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“…As a result, only 20 EA2 cases from 14 pedigrees and 3 EA1 cases from one genetically confirmed pedigree were included in this study (Figure 1). Clinical information of 11 cases from nine pedigrees are summarized in Table 1, wherein eight pedigrees have been published as Japanese EA2 cases, 9‐15 and one pedigree was an EA2 family case with a novel heterozygous variant in the CACNA1A gene (c. 758A>G, p. His253Arg) 16 . Two cases in family 2 in Table 1 had two heterozygous variants in the CACNA1A gene,c.383C>T (p.P128L), which has an unknown significance, and c.3575delA (p.N1192A fs*49), which was most likely pathogenic 9 .…”

Section: Resultsmentioning

confidence: 99%

A nationwide survey of episodic ataxia in Japan

Kubota

Hama

Sugiura

et al. 2021

Neurology & Clinical Neurosc

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Background Episodic ataxia (EA) is a rare inherited disorder characterized by recurrent cerebellar ataxic attacks. Given the limited number of EA case reports in Japan, the current status of EA medical conditions has become obscure, including the number of patients genetically confirmed to have EA and the clinical care these patients received. Aim We aimed to address the current status of EA medical conditions in Japan by investigating the total number of patients genetically confirmed to have the disease and their clinical characteristics. Methods We conducted a two‐step survey, primarily a nationwide survey using a round‐trip postcard for medical institutions expected to care for EA patients. As a secondary investigation, more detailed clinical information for each case was obtained using a written questionnaire. Furthermore, we explored the literature, including EA case reports in Japan. Results Our survey showed the clinical information of 20 EA type 2 (EA2) cases from 14 pedigrees, as confirmed by genetic analysis. In addition to cerebellar ataxic symptoms, clinical manifestations of the included patients were broad, including dizziness, balance disturbance, headache, epilepsy, and psychomotor developmental delay. Conclusion The number of patients with genetically confirmed EAs is currently limited in Japan, and a significant number of them may remain undiagnosed. We believe that the development of diagnostic strategies for EA has clinical benefits.

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Section: Resultsmentioning

confidence: 99%

A nationwide survey of episodic ataxia in Japan

Kubota

Hama

Sugiura

et al. 2021

Neurology & Clinical Neurosc

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“…Similar clinical symptoms of refractory seizures, muscular hypotonia and progressive ataxia are seen in our cases. Kaido et al 4 report two cases of EA2 with PPR in EEG. A novel single base deletion (c.3575delA) in CACNA1A was uncovered.…”

Section: Discussionmentioning

confidence: 98%

“…There are only two reports on a CACNA1A-related generalized epileptic seizure 3 and a photoparoxysmal response (PPR). 4 Muscular hypotonia or muscular atrophy has also been reported to be associated with CACNA1A gene. 5 …”

Section: Introductionmentioning

confidence: 99%

Identification of a novel CACNA1A mutation in a Chinese family with autosomal recessive progressive myoclonic epilepsy

Y¹,

Wang²,

Liu³

et al. 2017

NDT

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BackgroundProgressive myoclonic epilepsy (PME) is a heterogeneous neurodegenerative disorder, which is commonly manifested with refractory seizures and neurologic deterioration. The prognosis of PME is poor, so early diagnosis of PME is critical. The aim of our study is to identify the novel pathogenic gene in a Chinese family with PME, which may be helpful in future.Subjects and methodsA three-generation consanguineous Chinese Han family with PME was recruited. A novel homozygous variant was identified by the genetic technique of exome sequencing and certificated by Sanger sequencing and functional prediction.ResultsA novel homozygous variant, c.6975_6976insCAG, in the CACNA1A was identified in the PME family. The novel variant encoding the alpha-1A subunit of the calcium channel Cav2.1 was found in two siblings in the Chinese family and was absent in 50 normal controls. Our research indicates that the homozygous c.6975_6976insCAG might be the pathogenic mutation for PME.ConclusionAs a molecular diagnostic strategy, our research explores the mutation gene spectrum of PME and has resulted in significant predictions for genetic counseling.

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“…In 10 out of these 21 families, IEDs could be detected [36][37][38][39][40][41]. Notably, IEDs were also detected in several other EA2 families with no history of seizures [41,42,52,53]. Generalized 3 Hz spike-wave discharges were a recurrent EEG pattern [37,39,41,54,55].…”

Section: Review Of the Literaturementioning

confidence: 91%

“…Concerning EA2, numerous reports described IEDs [36][37][38][39][40][41][42]. Very few cases reported additional information on EEG findings, which were reported to be normal [43] or with interposed slowing [36,40].…”

Section: Review Of the Literaturementioning

confidence: 99%

The electrophysiological footprint of CACNA1A disorders

et al. 2021

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Objectives CACNA1A variants underlie three neurological disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). EEG is applied to study their episodic manifestations, but findings in the intervals did not gain attention up to date. Methods We analyzed repeated EEG recordings performed between 1994 and 2019 in a large cohort of genetically confirmed CACNA1A patients. EEG findings were compared with those of CACNA1A-negative phenocopies. A review of the related literature was performed. Results 85 EEG recordings from 38 patients (19 EA2, 14 FHM1, 5 SCA6) were analyzed. Baseline EEG was abnormal in 55% of cases (12 EA2, 9 FHM1). The most common finding was a lateralized intermittent slowing, mainly affecting the temporal region. Slowing was more pronounced after a recent attack but was consistently detected in the majority of patients also during the follow-up. Interictal epileptic discharges (IEDs) were detected in eight patients (7 EA2,1 FHM1). EEG abnormalities and especially IEDs were significantly associated with younger age at examination (16 ± 9 vs 43 ± 21 years in those without epileptic changes, p = 0.003) and with earlier onset of disease (1 (1–2) vs 12 (5–45) years, p = 0.0009). EEG findings in CACNA1A-negative phenocopies (n = 15) were largely unremarkable (p = 0.03 in the comparison with CACNA1A patients). Conclusions EEG abnormalities between attacks are highly prevalent in episodic CACNA1A disorders and especially associated with younger age at examination and earlier disease onset. Our findings underpin an age-dependent effect of CACNA1A variants, with a more severe impairment when P/Q channel dysfunction manifests early in life.

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Episodic ataxia type 2 manifests as epileptiform electroencephalographic activity with no epileptic attacks in two family members

Cited by 9 publications

References 8 publications

A nationwide survey of episodic ataxia in Japan

A nationwide survey of episodic ataxia in Japan

Identification of a novel CACNA1A mutation in a Chinese family with autosomal recessive progressive myoclonic epilepsy

The electrophysiological footprint of CACNA1A disorders

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