Education
Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a neurologic disorder characterized in most cases by early-onset seizures and variably impaired intellectual development (ID). The severity of neurologic impairment is highly variable: some patients may have refractory seizures and be bedridden with no meaningful speech, whereas others may have treatment-responsive seizures and achieve normal psychomotor development (summary by Li et al., 2019)
The CSNK2B gene encodes a regulatory subunit of casein kinase II (CK2), a highly conserved ubiquitous enzyme consisting of subunits alpha (CSNK2A1; 115440), alpha-prime (CSNK2A2; 115442), and beta. It is present in high levels in the brain and appears to be constitutively active. Animal models suggest that CK2 may play a role in dopamine signaling (summary by Poirier et al., 2017; Yang et al., 2018).
Síndrome do Neurodesenvolvimento de Poirier-Bienvenur, 2020. Note: Electronic Article. [Full Text]
The Ministry of Health defines a rare disease as one that affects 1 in 2000 individuals. The Poirier-Bienvenur Neurodevelopment Syndrome (also known by the acronym POBINDS) can be considered ULTRA - RARA, having no estimated incidence and having about 14 cases published so far. This small number is probably also due to the fact that this “syndrome” was only known in 2017, when the first, published in 2017 (Poirier K, 2017). The symptoms described in these cases include early-onset seizures and a wide variety of neurological symptoms, from seizures that do not improve with medications and delayed psychomotor development to patients with well-controlled seizures and near-normal psychomotor development. POBINDS is caused when we have a mutation in the gene called CSNK2B in only one of the alleles (one of the copies of our genetic material) being considered an autosomal dominant disease. This gene is on chromosome number 6. In all cases in the literature, the mutations in CSNK2B occurred 'again' which is the term that is used in genetics to explain that the inheritance was not inherited from either the individual's father or mother, it just happened by chance. Genetic variations that occur at random affect about 3% of individuals even without any risk factor.
Michelle Ernst; C. Working Group; Zöe Powis, CSNK2B: A Novel Cause of Neurodevelopmental Disease and Epilepsy, Collaborators: Columbia University, Conference: Annual Clinical Genetics Meeting (ACMG) 2019, [Full Text]
Here we describe an additional 17 individuals with a neurodevelopmental phenotype who carry a variant in CSNK28. Of the 20 identified cases, including those newly described in this series and the three previously reported, there were 16 males and four females. Epilepsy was reported in 75%, and all of them had seizure onset in the first three years of life. All cases had some degree of developmental delay and/or intellectual disability, ranging from mild developmental delay to severe intellectual disability. Some degree of speech impairment was also described in every case, and motor delay or impairment. Additional findings included hypotonia, behavioral issues, autism/autistic features, endocrine abnormalities, cardiac issues, hearing loss, and genitourinary issues. More than half had dysmorphic features, most of which were reported to be minor. This robust series of patients solidify the association between CSNK2B and neurodevelopmental disease and allows for further characterization of the phenotypic spectrum seen in this condition, including infantile-onset epilepsy with myoclonic seizures.
Li, J., Gao, K., Cai, S., Liu, Y., Wang, Y., Huang, S., Zha, J., Hu, W., Yu, S., Yang, Z., Xie, H., Yan, H., Wang, J., Wu, Y., Jiang, Y. Germline de novo variants in CSNK2B in Chinese patients with epilepsy. Sci. Rep. 9: 17909, 2019. Note: Electronic Article. [Full Text]
In this study, 816 suspected hereditary epilepsy patients tested using trio-based whole-exome sequencing (WES). 10 de novo pathogenic or likely pathogenic variants of CSNK2B in nine probands were identified. Six of the nine epileptic patients had ID/DD. The age of seizure onset of these nine patients with CSNK2B variants ranged from 2–12 months. Eight patients had an age of seizure onset of fewer than 6 months. The epilepsy of most probands (8/9) was a generalized tonic-clonic seizure and clustered (6/9). Most patients had normal electroencephalogram (5/9) and brain magnetic resonance image (7/9) results. Levetiracetam was the most commonly used drug in seizure-free patients (5/7).
Nakashima, M., Tohyama, J., Nakagawa, E., Watanabe, Y., Siew, C. G., Kwong, C. S., Yamoto, K., Hiraide, T., Fukuda, T., Kaname, T., Nakabayashi, K., Hata, K., Ogata, T., Saitsu, H., Matsumoto, N. Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures. J. Hum. Genet. 64: 313-322, 2019. [Full Text]In this study, we describe four patients with neurodevelopmental disorders possessing de novo variants in CSNK2A1 or CSNK2B. Using whole-exome sequencing, we detected 2 de novo variants in CSNK2A1 in two unrelated Japanese patients and two novels de novo variants in CSNK2B in Japanese and Malaysian patients. All four patients showed mild to profound intellectual disabilities, developmental delays, and various types of seizures.
Poirier, K., Hubert, L., Viot, G., Rio, M., Billuart, P., Besmond, C., Bienvenu, T. CSNK2B splice site mutations in patients cause intellectual disability with or without myoclonic epilepsy. Hum. Mutat. 38: 932-941, 2017. [Full Text]The study reports the results from the screening of 2 patients diagnosed with intellectual disability (ID) using exome sequencing. The two patients presented developmental delay with minor facial dysmorphia. One of them presented pharmacoresistant myoclonic epilepsy. The study confirmed that protein kinase CK2 plays a major role in the brain. This study adds knowledge to the increasingly growing list of causative and candidate genes in ID and epilepsy and highlights CSNK2B as a new gene for neurodevelopmental disorders.
This is a letter to the editor of the previous study to confirm the existence of 1 more patient with intellectual disability and myoclonic epilepsy
and the exome sequencing showed a mutation in CSNK2B.
CSNK2B and cancer
