The spectrum of epilepsy in children with 15q13.3 microdeletion syndrome

Whitney, Robyn; Nair, Arjun; McCready, Elizabeth; Keller, Anne; Adil, Ishita Siddiq; Aziz, Aly Shah; Borys, Oksana; Siu, Kaitlyn; Shah, Chintan; Meaney, Brandon; Jones, Kay S.; RamachandranNair, Rajesh

doi:10.1016/j.seizure.2021.09.016

Cited by 15 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All 15 individuals with duplication of 9q34.3 had focalonset seizures that were rarely drug-resistant, without any individual annotated with a neurodevelopmental disorder or polymicrogyria despite the presence of the GRIN1, which can cause polymicrogyria when affected by gain-of-function variants 47 . Sixteen of 24 individuals carrying deletions at 15q13.3 [31.06-32.51 Mb] had generalized absence seizures (OR = 10.5, unadjusted P = 3.70 × 10 −8 , minP-adjusted P = 1 × 10 −5 ), in line with the primary seizure type reported in carriers of the 15q13.3 deletion 66 . Finding generalized myoclonic seizures in half of the carriers of the 22q11.2 [19.67-19.96 Mb] deletion further confirmed TBX1 67 , the known causal gene for the 22q11.21 deletion/ DiGeorge syndrome 48 .…”

Section: Characterization Of the Clinical Subphenotypes Enriched In T...supporting

confidence: 57%

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

et al. 2023

View full text Add to dashboard Cite

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice.

show abstract

Section: Characterization Of the Clinical Subphenotypes Enriched In T...supporting

confidence: 57%

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The 15q13.3 microdeletion has been associated with a 34-fold risk for developing GGE (Figure 2A) [48]. While 15q13.3del CNVs have also been associated with childhoodonset absence seizures and can also present with atypical symptoms such as resistance to anti-seizure medications (ASMs) or intellectual disability, only about one third of people with this CNV have epilepsy [49]. 16p11.2 deletions and duplications affect approximately 3 in every 10,000 individuals and epilepsy or seizures have been reported in approximately 25% of patients with a deletion and in up to almost 30% of duplication carriers [50].…”

Section: Monogenic and Complex Epilepsiesmentioning

confidence: 99%

Complexity in Genetic Epilepsies: A Comprehensive Review

Rastin,

Schenkel,

Sadikovic

2023

IJMS

View full text Add to dashboard Cite

Epilepsy is a highly prevalent neurological disorder, affecting between 5–8 per 1000 individuals and is associated with a lifetime risk of up to 3%. In addition to high incidence, epilepsy is a highly heterogeneous disorder, with variation including, but not limited to the following: severity, age of onset, type of seizure, developmental delay, drug responsiveness, and other comorbidities. Variable phenotypes are reflected in a range of etiologies including genetic, infectious, metabolic, immune, acquired/structural (resulting from, for example, a severe head injury or stroke), or idiopathic. This review will focus specifically on epilepsies with a genetic cause, genetic testing, and biomarkers in epilepsy.

show abstract

“…Two studies about SE in patients with deletion of 15q13.3 were included. Four patients with SE were identified: two of them developed ESES [65,66], two experienced absence SE and one had focal to bilateral CSE [65]. Age at SE onset ranged between 3 and 7 years of age.…”

Section: Other Cdaementioning

confidence: 99%

“…Two studies described the occurrence of ESES in Del15q13.3 patients [65,66]. Kevelam et al hypothesize that the involvement of CHRNA7 in the microdeletion is likely responsible for the occurrence of ESES, due to its relationship with other forms of sleep-related epilepsy.…”

Section: Other Cdaementioning

confidence: 99%

Status Epilepticus in Chromosomal Disorders Associated with Epilepsy: A Systematic Review

Bergonzini

Pruccoli

Pettenuzzo

et al. 2023

Genes

View full text Add to dashboard Cite

Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding SE occurrence in these patients is lacking. A systematic scoping review was conducted to outline current literature evidence about clinical features, treatments, and outcomes of SE in pediatric and adult patients with CDAE. A total of 373 studies were identified with the initial search; 65 of these were selected and regarded as SE in Angelman Syndrome (AS, n = 20), Ring 20 Syndrome (R20, n = 24), and other syndromes (n = 21). Non-convulsive status epilepticus (NCSE) is frequently observed in AS and R20. No specific, targeted therapies for SE in CDAE are available to date; anecdotal reports about SE treatment are described in the text, as well as various brief- and long-term outcomes. Further evidence is needed to precisely portray the clinical features, treatment options, and outcomes of SE in these patients.

show abstract

The spectrum of epilepsy in children with 15q13.3 microdeletion syndrome

Cited by 15 publications

References 30 publications

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Complexity in Genetic Epilepsies: A Comprehensive Review

Status Epilepticus in Chromosomal Disorders Associated with Epilepsy: A Systematic Review

Contact Info

Product

Resources

About