Focal cortical malformations in children with early infantile epilepsy and <i><scp>PCDH</scp>19</i> mutations: case report

Kurian, Mary; Korff, Christian; Ranza, Emmanuelle; Bernasconi, Andrea; Lübbig, Anja; Nangia, Srishti; Ramelli, Gian Paolo; Wohlrab, Gabriele; Nordli, Douglas R.; Bast, Thomas

doi:10.1111/dmcn.13595

Cited by 67 publications

(57 citation statements)

References 16 publications

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“…There were only two cases that had nonspecific abnormalities on cranial MRI. Although some studies found cortical dysplasia in PCDH19 mutation patients and mouse models(Kurian et al, 2018;Pederick et al, 2018), this was not found in our patients. Interictal EEG showed transient focal or multiple epileptiform discharges in only four patients.…”

contrasting

confidence: 94%

“…After discovering that the level of allopregnanolone and steroidogenesis decreased (Tan et al, ; Trivisano et al, ), clinical trials began with ganaxolone, a synthetic analog of isoprogesterone (Tan et al, ). Surgical excision can reduce seizures in patients with cortical dysplasia (Kurian et al, ). Children with PCDH19 ‐GCE had better responsiveness to benzodiazepines in the acute stage, and midazolam could control epileptic seizures.…”

Section: Discussionmentioning

confidence: 99%

“…After discovering that the level of allopregnanolone and steroidogenesis decreased (Tan et al, 2015;Trivisano et al, 2017), clinical trials began with ganaxolone, a synthetic analog of isoprogesterone (Tan et al, 2015). Surgical excision can reduce seizures in patients with cortical dysplasia (Kurian et al, 2018 AEDs. This may suggest that if we met a PCDH19 family in clinic, the medication characteristics of proband in the family can guide the treatment of other patients in the same family.…”

Section: Discussionmentioning

confidence: 99%

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Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

Liu

et al. 2019

Brain and Behavior

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Background PCDH19 has become the second most relevant gene in epilepsy after SCN1A. Seizures often provoked by fever.MethodsWe screened 152 children with fever‐sensitive epilepsy for gene detection. Their clinical information was followed up.ResultsWe found eight PCDH19 point mutations (four novel and four reported) and one whole gene deletion in 10 female probands (seven sporadic cases and three family cases) who also had cluster seizures. The common clinical features of 16 patients in 10 families included fever‐sensitive and cluster seizures, mainly focal or tonic‐clonic seizures, and absence of status epilepticus, normal intelligence, or mild‐to‐moderate cognitive impairment, the onset age ranges from 5 months to 20 years. Only four patients had multiple or focal transient discharges in interictal EEG. Focal seizures originating in the frontal region were recorded in four patients, two from the parietal region, and one from the occipital region.Conclusion PCDH19 mutation can be inherited or de novo. The clinical spectrum of PCDH19 mutation includes PCDH19 Girls Clustering Epilepsy with or without mental retardation, psychosis, and asymptomatic male. The onset age of PCDH19 Girls Clustering Epilepsy can range from infancy to adulthood. Sisters in the same family may be sensitive to the same antiepileptic drugs. And our report expands the mutation spectrum of PCDH19 Girls Clustering Epilepsy.

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confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

Liu

et al. 2019

Brain and Behavior

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“…Unusual focal temporal-occipital anomalies can be identified in a few patients and raise the possibility of a structural lesion. Interestingly, in the literature, a recent study (Kurian et al, 2018) has reported, for the first time, an association between focal cortical malformations (focal cortical dysplasia and nodular heterotopia) and early-infantile epilepsy and PCDH19 mutation in five female children. Two of these patients underwent surgery with an improvement in seizure control.…”

Section: Discussionmentioning

confidence: 99%

Early and long‐term electroclinical features of patients with epilepsy and PCDH19 mutation

Chémaly

Losito

Pinard

et al. 2018

Epileptic Disorders

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Aims. Protocadherin 19 (PCDH19) mutations have been identified in epilepsy in females with mental retardation as well as patients with a “Dravet‐like” phenotype. We aimed to elucidate the electroclinical phenotype associated with PCDH19 mutation, which is currently difficult to identify at onset leading to a delay in diagnosis. Methods. We retrospectively reviewed clinical and EEG data for 13 consecutive patients with PCDH19 mutations or deletions diagnosed at our centers from 2009 to 2011, and followed these patients into adolescence and adulthood. Results. We identified a specific temporal sequence of electroclinical manifestations, identified as three main stages. During the first two years of life, previously healthy girls presented with clusters of afebrile focal seizures. Early seizures were recorded on video‐EEG in 10/13 patients, and were focal (n=8) with temporo‐occipital and frontal onset. Three patients with strictly stereotyped focal seizures underwent a pre‐surgical work‐up. Two patients started with generalized seizures, one presenting with early‐onset atypical absences and the other generalized tonic‐clonic seizures. During the course of the disease, from two to 10 years, seizures became fever‐sensitive and continued to recur in clusters, although these were less frequent. Seizures were mainly described by eyewitnesses as generalized tonic‐clonic, even though three of five seizures, recorded on EEG, showed a focal onset with fast bilateral spread. Atypical absences and fever‐induced tonic‐clonic seizures remained frequent in only one patient until the age of 16 years. No specific treatment or combination appeared to be more effective over another. Various degrees of cognitive or behavioural impairment were reported for all patients, but it was in the second decade that behavioural disturbances prevailed with hetero‐aggressiveness and behaviour associated with frontal lobe abnormalities leading to psychosis in two. Conclusions. Early recognition of the above features should improve early diagnosis and long‐term management of patients with epilepsy and PCDH19 mutations.

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“…Initial studies on PCDH19 knock‐out mice (Pederick et al , ) revealed no gross brain morphological defects, suggesting that PCDH19 was dispensable for brain development in species other than zebrafish. However, more recent studies reported the presence of cortical malformations in EIEE9 patients (Kurian et al , ; Pederick et al ., ) reinforcing the idea of PCDH19 involvement in cellular processes that ultimately influence brain morphology, such as neuronal migration.…”

Section: Mutations In Pcdh19 Gene and Encephalopathiesmentioning

confidence: 99%

The Role of Protocadherin 19 (PCDH19) in Neurodevelopment and in the Pathophysiology of Early Infantile Epileptic Encephalopathy‐9 (EIEE9)

Gerosa

Francolini

Bassani

et al. 2019

Developmental Neurobiology

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PCDH19 is considered one of the most clinically relevant genes in epilepsy, second only to SCN1A. To date about 150 mutations have been identified as causative for PCDH19‐female epilepsy (also known as early infantile epileptic encephalopathy‐9, EIEE9), which is characterized by early onset epilepsy, intellectual disabilities, and behavioral disturbances. Although little is known about the physiological role of PCDH19 and the pathogenic mechanisms that lead to EIEE9, in this review, we will present latest researches focused on these aspects, underlining protein expression, its known functions and the mechanisms by which the protein acts, with particular interest in PCDH19 extracellular and intracellular roles in neurons.

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Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report

Cited by 67 publications

References 16 publications

Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

Early and long‐term electroclinical features of patients with epilepsy and PCDH19 mutation

The Role of Protocadherin 19 (PCDH19) in Neurodevelopment and in the Pathophysiology of Early Infantile Epileptic Encephalopathy‐9 (EIEE9)

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