A Novel Mutation in KCDT7 Gene in an Indian Girl With Progressive Myoclonus Epilepsy

Dudipala, Sai Chandar; Prashanthi, M; Chennadi, Amith Kumar

doi:10.7759/cureus.13447

Cited by 3 publications

(10 citation statements)

References 14 publications

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“…KCTD7 -PME patients display myoclonic or generalized tonic-clonic seizures with abnormal electroencephalograms (EEGs) featuring frequent multifocal and/or generalized spike waves associated with an excess of slow activity ( Dai et al, 2019 ; Dudipala et al, 2021 ; Farhan et al, 2014 ; Kousi et al, 2012 ; Mastrangelo et al, 2019 ; Mei et al, 2019 ; Van Bogaert et al, 2007 ; Blumkin et al, 2012 ; Moen et al, 2016 ; Staropoli et al, 2012 ; Krabichler et al, 2012 ). We performed chronic video-EEG monitoring in 2-month-old moving young adult Kctd7 -deficient mice and detected robust spontaneous epileptiform activity, consisting of interictal multifocal fast cortical spike and polyspike discharges in eight of ten animals recorded ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Mutations in the potassium channel tetramerization domain-containing (KCTD) 7 ( KCTD7 ) gene cause progressive myoclonic epilepsy (PME) 3 ( ), a rare but often crippling neurodevelopmental and epileptic disorder. KCTD7 -related progressive myoclonic epilepsy ( KCTD7 -PME) has been reported in over 55 patients with more than 40 unique variants ( Burke et al, 2021 ; Dai et al, 2019 ; Dudipala et al, 2021 ; Farhan et al, 2014 ; Kousi et al, 2012 ; Kozina et al, 2020 ; Lindy et al, 2018 ; Mastrangelo et al, 2019 ; Mei et al, 2019 ; Metz et al, 2018 ; Rahman and Fatema, 2021 ; Vairo et al, 2017 ; Van Bogaert et al, 2007 ; Blumkin et al, 2012 ; Moen et al, 2016 ). Affected patients carry homozygous or compound heterozygous mutations, whereas heterozygous family members are neurologically unaffected ( Metz et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Kctd7 deficiency induces myoclonic seizures associated with Purkinje cell death and microvascular defects

Liang

Alevy

Akhanov

et al. 2022

Disease Models &Amp; Mechanisms

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Mutations in the potassium channel tetramerization domain-containing 7 (KCTD7) gene are associated with a severe neurodegenerative phenotype characterized by childhood onset of progressive and intractable myoclonic seizures accompanied by developmental regression. Kctd7 (EPM3) is a member of a large family of progressive myoclonic epilepsy (EPM) syndromes displaying a broad spectrum of clinical severity. Animal models of Kctd7-related disease are lacking, and little is known regarding how Kctd7 protein defects lead to epilepsy and cognitive dysfunction. We characterized brain Kctd7 expression patterns during development and show it is selectively enriched in specific regions as the brain matures. We further demonstrate that Kctd7-deficient mice develop seizures and locomotor defects with features similar to those observed in human KCTD7-associated disease. We also show that Kctd7 is required for Purkinje cell survival in the cerebellum and that selective degeneration of these neurons is accompanied by defects in cerebellar brain microvascular organization and patterning. Together, these results define a new model for Kctd7- associated epilepsy and identify Kctd7 as a modulator of neuron survival and excitability linked to microvascular alterations in vulnerable regions.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kctd7 deficiency induces myoclonic seizures associated with Purkinje cell death and microvascular defects

Liang

Alevy

Akhanov

et al. 2022

Disease Models &Amp; Mechanisms

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“…KCTD7 biallelic pathogenic variants are predominantly associated with early onset PME, and seizures are the initial symptom in most children (i.e., 60%-70%). 14,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Myoclonic seizures are the most frequent seizure type observed at disease onset, followed by generalized tonic-clonic, generalized clonic, generalized atonic, and generalized tonic seizures. Over time, nearly all children in our cohort and in the literature developed myoclonic seizures.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the age at symptom onset was similar between our cohort and the literature, occurring in the first year and a half of life. 14,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] However, in the literature disease onset could occur as late as 36 months. 15,24,27 Progressive neurological decline with or without stabilization following a period of normal development was observed in one third of our cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Forty-one records were retrieved and assessed for eligibility. Twenty-three studies were included, [14][15][16][17][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] and 18 studies were excluded 13,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] for the following reasons: variables of interest not reported, 13,[41][42][43][44][47][48][49][50][51]53,…”

Section: Systematic Reviewmentioning

confidence: 99%

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KCTD7‐related progressive myoclonic epilepsy: Report of 42 cases and review of literature

Yoganathan,

Whitney,

Thomas

et al. 2024

Epilepsia

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ObjectiveKCTD7‐related progressive myoclonic epilepsy (PME) is a rare autosomal‐recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort.MethodsFamilies with molecularly confirmed diagnoses of KCTD7‐related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging‐related variables were collected and summarized.ResultsForty‐two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75–22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty‐one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5–21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7‐related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3–18 years).SignificanceThis study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7‐related disorders. Early onset drug‐resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.

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A case of a 6-year-old girl with a rare compound heterozygous mutation of KCTD7 presenting with progressive myoclonic epilepsy

Badv,

Shariatmadari,

Bayat

et al. 2024

Egypt J Med Hum Genet

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Background Progressive myoclonic epilepsy is a clinically and genetically heterogeneous group of diseases characterized by myoclonic seizures, drug-resistant epilepsy and neurodevelopmental regression. The disease is attributed to mutations in KCTD7 (a member of the potassium channel tetramerization domain). Case presentation We report the case of a 6-year-old girl with compound heterozygous mutation in KCTD7. Whole-exome sequencing was carried out to detect the mutations followed by Sanger sequencing of the patient in addition to the unaffected parents which confirmed the diagnosis. The first mutation [c. 202A > G (p.Thr68Ala)] was inherited from mother and the second one [c. 458G > A (p.Arg153His)] was inherited from father. Conclusions To our knowledge, this is the first report of compound heterozygousKCTD7-related progressive myoclonic epilepsy in Iran with c.202A > G in particular as a novel mutation. Our findings widen the scope of our knowledge of the underlying genetic etiology of the aforementioned disease which can further help us in the genetic diagnosis of these patients.

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A Novel Mutation in KCDT7 Gene in an Indian Girl With Progressive Myoclonus Epilepsy

Cited by 3 publications

References 14 publications

Kctd7 deficiency induces myoclonic seizures associated with Purkinje cell death and microvascular defects

Kctd7 deficiency induces myoclonic seizures associated with Purkinje cell death and microvascular defects

KCTD7‐related progressive myoclonic epilepsy: Report of 42 cases and review of literature

A case of a 6-year-old girl with a rare compound heterozygous mutation of KCTD7 presenting with progressive myoclonic epilepsy

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