For those interested in neurodevelopmental conditions, consider Okur-Chung and Poirier-Bienvenu syndromes.
Okur-Chung neurodevelopmental syndrome is a rare genetic syndrome caused by variants or mutation in the CSNK2A1 gene. Behaviorally it appears as motor delays, developmental disabilities, intellectual disabilities, sleep disorders, and behavioral issues. It appears in both males and females. Probably fewer than 200 cases have been identified worldwide.
Poirier-Bienvenu neurodevelopmental syndrome is another rare genetic syndrome caused by variants or mutations in the CSNK2B gene. It is characterized by seizures during infancy and early childhood and developmental disabilities, Some children have more severe problems than others. There may be 80 to 100 cased worldwide.
Demetra Ballardin et al. (2022) of Institute of Psychiatry and Neuroscience and the Hôpital Sainte Anne of Paris (FR) compared and contrasted the two disorders.
In recent years, variants in the catalytic and regulatory subunits of the kinase CK2 have been found to underlie two different, yet symptomatically overlapping neurodevelopmental disorders, termed Okur-Chung neurodevelopmental syndrome (OCNDS) and Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). Both conditions are predominantly caused by de novo missense or nonsense mono-allelic variants. They are characterized by a generalized developmental delay, intellectual disability, behavioral problems (hyperactivity, repetitive movements and social interaction deficits), hypotonia, motricity and verbalization deficits. One of the main features of POBINDS is epilepsies, which are present with much lower prevalence in patients with OCNDS. While a role for CK2 in brain functioning and development is well acknowledged, these findings for the first time clearly link CK2 to defined brain disorders. Our review will bring together patient data for both syndromes, aiming to link symptoms with genotypes, and to rationalize the symptoms through known cellular functions of CK2 that have been identified in preclinical and biochemical contexts. We will also compare the symptomatology and elaborate the specificities that distinguish the two syndromes.
Because these are genetic disorders and are quite rare, there is essentially no evidence base about treatments or interventions. One would, people sometimes say, “treat the symptoms.” There would be medical management of seizures, for example. And one could expect to behavioral methods to manage learning and socialization. Identify specific behaviors an individual needs to acquire; analyze the behaviors systematically; make environmental adaptations to alter the frequency, intensity, duration, or accuracy of those behaviors; monitor changes.
Does that sound familiar?
Realizing that educational methods would be awfully similar (even the same?) regardless of the syndrome underscores the futility of seeking causes for disorders. In these disorders, researchers know the cause right down to molecules. Knowing the cause does not help us know what to do.
I’m happy with establishing environmental causes. We know how to do that using functional assessment and analysis. There the causes are actionable. And I understand that knowing there is a biological cause helps some folks feel relief from feelings of responsibility for children’s problems.
I wish, however, we could put aside the unproductive worship of “causes,” and spend our time and effort on helping kids succeed.
References
Akahira-Azuma, M., Tsurusaki, Y., Enomoto, Y., Mitsui, J., & Kurosawa, K. (2018). Refining the clinical phenotype of Okur–Chung neurodevelopmental syndrome. Human Genome Variation, 5(1), 18011.
Ballardin, D., Cruz-Gamero, J. M., Bienvenu, T., & Rebholz, H. (2022). Comparing two neurodevelopmental disorders linked to CK2: Okur-Chung neurodevelopmental syndrome and Poirier-Bienvenu neurodevelopmental syndrome—two sides of the same coin?. Frontiers in Molecular Biosciences, 9, 850559. https://doi.org/10.3389/fmolb.2022.850559
Chiu, A. T. G., Pei, S. L. C., Mak, C. C. Y., Leung, G. K. C., Yu, M. H. C., Lee, S. L., ... & Chung, B. H. Y. (2018). Okur‐Chung neurodevelopmental syndrome: Eight additional cases with implications on phenotype and genotype expansion. Clinical Genetics, 93(4), 880-890.
Duz, M.B., Lasa-Aranzasti, A., Cazurro-Gutiérrez, A., Hackett, A., Cueto-González, A. M., Périco, A. A., Ruivenkamp, C. A. L., Gómez-Andrés, D., Curic, E., Palmer, E. E., Jones, E. A., Aliu, E., Veenstra-Knol, H. E., Goel, H., Marti, I. C., Legebeke, J., Wassink-Ryuiter, J. S. K., Ewans, L., Thomas, M. A., Codina-Solà, M., Hollander, N. S., Martínez-Gil, N., Gates, R., Kana, S. L., McKee, S., Banka, S., Sell, S., & Chung, W. K. (2026). Clinical characterization and genotype–phenotype correlations in Chilton-Okur-Chung syndrome. BMC Med Genomics. https://doi.org/10.1186/s12920-026-02448-w
Lippa, N., Mulhern, M., Florido, M. E., Earley, C., & Sands T. T. (2024). CSNK2B-related neurodevelopmental disorder. In M. P. Adamn, S. Bick, G. M. Mirzaa, S. E., Wallace, & A Amemiya (Eds.), GeneReviews. https://www.ncbi.nlm.nih.gov/books/n/gene/csnk2b-ndd/