<i>CSNK2B</i>: A broad spectrum of neurodevelopmental disability and epilepsy severity

Ernst, Michelle; Baugh, Evan H.; Thomas, Amanda L.; Bier, Louise; Lippa, Natalie; Stong, Nicholas; Mulhern, Maureen; Kushary, Sulagna; Akman, Cigdem I.; Heinzen, Erin L.; Yeh, Raymond; Bi, Weimin; Hanchard, Neil A.; Burrage, Lindsay C.; Leduc, Magalie S.; Chong, Josephine S. C.; Bend, Renee; Lyons, Michael J.; Lee, Jennifer A.; Suwannarat, Pim; Brilstra, Eva H.; Simon, Marleen; Koopmans, Marije; Binsbergen, Ellen van; Groepper, Daniel; Fleischer, Julie; Nava, Caroline; Keren, Boris; Mignot, Cyril; Mathieu, Sophie; Mancini, Grazia M.S.; Madan‐Khetarpal, Suneeta; Infante, Elena; Bluvstein, Judith; Seeley, Andrea; Bachman, Kristine; Klee, Eric W.; Schultz‐Rogers, Laura; Hasadsri, Linda; Barnett, Sarah S.; Ellingson, Marissa S.; Ferber, Matthew J.; Narayanan, Vinodh; Ramsey, Keri; Rauch, Anita; Joset, Pascal; Steindl, Katharina; Sheehan, Theodore; Poduri, Annapurna; Vasquez, Alejandra; Ruivenkamp, Claudia; White, Susan; Pais, Lynn; Monaghan, Kristin G.; Goldstein, David B.; Sands, Tristan T.; Aggarwal, Vimla S.

doi:10.1111/epi.16931

Cited by 19 publications

(52 citation statements)

References 19 publications

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“…Our cohort reported nine patients with different CSNK2B mutations. Age at onset did not differ from the data presented in the literature (median: 10 vs. 5.5 months; pvalue: 0.09) [1,3,6,[14][15][16]. Interestingly, all our patients displayed epilepsy, with generalized tonic-clonic seizure being the most common phenotype (67%), in agreement with previous studies [1,3,6,[14][15][16].…”

Section: Discussionsupporting

confidence: 89%

“…Our results confirmed such findings, with five (55%) patients presenting facial dysmorphism, as shown in Figure 2. Abnormalities of cranial size have also been described by Ernst et al, who reported two patients with microcephaly and four patients with macrocephaly [3]. In our cohort, 33% of cases presented microcephaly.…”

Section: Discussionsupporting

confidence: 85%

“…To our knowledge, only 50 cases have been reported in the literature. However, current evidence suggests that POBINDS could manifest with a wide range of symptoms, including early-onset epilepsy, a variable degree of intellectual disability (ID), developmental disability (DD), and growth abnormalities [ 1 , 2 , 3 ]. Such symptoms define a wide spectrum of phenotypes, ranging from well-controlled seizure and mild ID to intractable epilepsy, recurrent refractory status epilepticus (SE), and severe neurodevelopmental delay.…”

Section: Introductionmentioning

confidence: 99%

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Expanding Phenotype of Poirier–Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients

Orsini

Santangelo

Bravin

et al. 2022

Genes

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Background: Poirier–Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of CSNK2B. Methods: Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of CSNK2B mutation. Results: We reported nine unrelated patients with heterozygous de novo mutations of the CSNK2B gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of CSNK2B that have not been reported previously. Conclusion: Although it was not possible to assess a genotype–phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expanding Phenotype of Poirier–Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients

Orsini

Santangelo

Bravin

et al. 2022

Genes

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“…Epilepsy in POBINDS is also characterized by unaltered EEG and MRI. Being drug resistant, tonic–clonic seizures are the most frequent presentation [ 2 , 7 , 8 ]. The absence of a specific imaging pattern corroborated in both of our cases to a delayed diagnosis, as exemplified in Case #1 where sleep myoclonus was one of the differential diagnosis owing to the unaltered EEG.…”

Section: Discussionmentioning

confidence: 99%

“…Two de novo missense mutations (p.Asp32Asn and p.Asp32His) in the same CSNK2B codon, which is mutated in patient #2, have recently been associated with CDS [ 3 , 7 ]. Due to the modification of the CK2 structure, the closest CK2 catalytic subunit would be position 32, which could exert a more severe dysmorphic phenotype.…”

Section: Discussionmentioning

confidence: 99%

Two different presentations of de novo variants of CSNK2B: two case reports

et al. 2022

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Background Poirier–Bienvenu neurodevelopmental syndrome is a neurologic disorder caused by mutations in the CSNK2B gene. It is mostly characterized by early-onset seizures, hypotonia, and mild dysmorphic features. Craniodigital syndrome is a recently described disorder also related to CSNK2B, with a single report in the literature. Objective To report two unrelated cases of children harboring CSNK2B variants (NM_001320.6) who presented with distinct diseases. Case report Case 1 is a 7-month-old, Caucasian, female patient with chief complaints of severe hypotonia and drug-refractory myoclonic epilepsy, with a likely pathogenic de novo variant c.494A>G (p.His165Arg). Case 2 is a 5-year-old male, Latino patient with craniodigital intellectual disability syndrome subjacent to a de novo, likely pathogenic variant c.94G>T (p.Asp32Tyr). His dysmorphic features included facial dysmorphisms, supernumerary nipples, and left-hand postaxial polydactyly. Conclusion This report suggest that the CSNK2B gene may be involved in the physiopathology of neurodevelopmental disorders and variable dysmorphic features.

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Genomic analysis of “microphenotypes” in epilepsy

Stanley

Hostyk

Tran

et al. 2021

American J of Med Genetics Pt A

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Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as “all focal epilepsy” and “all genetic generalized epilepsy”. In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or “microphenotype” may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome‐wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau–Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A).

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CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity

Cited by 19 publications

References 19 publications

Expanding Phenotype of Poirier–Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients

Expanding Phenotype of Poirier–Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients

Two different presentations of de novo variants of CSNK2B: two case reports

Genomic analysis of “microphenotypes” in epilepsy

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