<i><scp>PCDH</scp>19</i>‐related epilepsy is associated with a broad neurodevelopmental spectrum

Smith, Lacey; Singhal, Nilika Shah; Achkar, Christelle Moufawad El; Truglio, Gessica; Sheidley, Beth Rosen; Sullivan, Joseph; Poduri, Annapurna

doi:10.1111/epi.14003

Cited by 72 publications

(98 citation statements)

References 32 publications

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“…This psychiatric phenotype is not frequent in DS. In line with this, Smith et al (2018) have underlined the prevalence of neuropsychiatric and behavioural disorders in their series of patients with PCDH19 mutation, mainly represented by autistic features, but also associated with obsessive compulsive symptoms. Despite various degrees of intellectual disability, motor development was normal in our patients, in contrast to DS patients in whom motor skills, especially coordination and gait disorders, are reported to be strongly impaired (Chieffo et al, 2011;Takayama et al, 2014).…”

Section: Discussionmentioning

confidence: 65%

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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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Section: Discussionmentioning

confidence: 65%

“…In line with this, Smith et al . () have underlined the prevalence of neuropsychiatric and behavioural disorders in their series of patients with PCDH19 mutation, mainly represented by autistic features, but also associated with obsessive compulsive symptoms.…”

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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“…The encoded protein is also a transcription factor involved in fetal telencephalic development and postmitotic neuron survival. 139 Dystonia, dyskinesia, chorea, MECP2-like features, and hand stereotypies in childhood are described in patients with MEF2C mutations, who also manifest DEE and childhood-onset epilepsy including myoclonic, atonic seizures, and infantile spasms. FOXG1-related disease is characterized by global neurodevelopmental delay, rather than neurological regression, often accompanied by poor feeding, irritability, hypotonia, postnatal microcephaly, lack of purposeful hand use, and visual inattention.…”

Section: Epilepsy Syndromes Associated With Prominent Stereotypiesmentioning

confidence: 99%

“…Other associations also include autistic features and behavioural issues, sleep disturbance, and hand stereotypies. 139 Dystonia, dyskinesia, chorea, MECP2-like features, and hand stereotypies in childhood are described in patients with MEF2C mutations, who also manifest DEE and childhood-onset epilepsy including myoclonic, atonic seizures, and infantile spasms. 140 Similar to MECP2, a number of genes causing epilepsy syndromes with prominent stereotypies encode for transcription factors, or proteins involved in transcriptional regulation.…”

Section: Epilepsy Syndromes Associated With Prominent Stereotypiesmentioning

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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“…And, our report found four novel mutations which expand the spectrum of PCDH19 mutations associated with epilepsy in females. All the patients in the study were female, with onset age ranging from 5 months to 20 years old, later than the 6 months to 3 years old reported in the literature (Smith et al, ). In our study, the patients with the onset age older than 3 years (5/16, 31.25%) were mainly the first and second generations of the families.…”

Section: Discussionmentioning

confidence: 71%

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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PCDH19‐related epilepsy is associated with a broad neurodevelopmental spectrum

Cited by 72 publications

References 32 publications

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

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

The expanding spectrum of movement disorders in genetic epilepsies

Novel and de novo mutation of PCDH19 in Girls Clustering Epilepsy

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