Research Explained: Okur-Chung neurodevelopmental syndrome: Eight additional cases with implications on phenotype and genotype expansion

Authors: A. T. G Chiu, S. L. C. Pei, C. C. Y. Mak, G. K. C. Leung, M. H. C. Yu, S. L. Lee, M. Vreeburg, R. Pfundt, I. van der Burgt, T. Kleefstra, T. M. T. Frederic, S. Nambot, L. Faivre, A. L. Bruel, M. Rossi, B. Isidor, S. Küry, B. Cogne, T. Besnard, M. Willems, M. R. F. Reijnders, and B. H. Y. Chung

Publication Date: December 10th, 2017

Research Explained By: Brad Davidson, CSNK2A1 Foundation Science Communication Intern

Link to article: https://onlinelibrary.wiley.com/doi/10.1111/cge.13196

Research Explained Summary:

In this case series, eight new patients with OCNDS were identified. The authors analyzed the symptoms present in these patients and combined their analysis with that of six previously characterized patients to create a better summary of what defines OCNDS. Specifically, 13/14 patients displayed intellectual disability. However, one patient entered school and their performance was assessed to be above average. Autism, sleep disorders, excessive temper tantrums, muscle weakness (hypotonia), and physical brain abnormalities were the most common neurodevelopmental symptoms found. Other common traits included failure to thrive, short stature, skin abnormalities, gastrointestinal issues, and immunological issues. In terms of characteristic facial features, microcephaly (small brain/head) was very common with 8/14 patients displaying this, while other features such as a round face, broad nose, and low-set ears were reported but were less common.

The genetic mutations present in OCNDS were also evaluated, including a total of 22 subjects across 4 studies reported to the date of publication of this paper. All mutations causing OCNDS were found in the CSNK2A1 gene, with most of them in an area of the gene that translates to a region known as the “protein kinase domain” of the protein that CSNK2A1 encodes, CK2α. Only two mutations found in these 22 patients fall outside of this specific region, indicating its importance for both proper function of the gene and overall human development. The most common mutation found among this cohort is called p.K198R and it is within this region.

Together, this study reported 8 new patients diagnosed with OCNDS and performed an analysis of all symptoms and genetic mutations found to date. The authors recommend that patients with OCNDS be seen by a clinical geneticist and receive comprehensive assessment from a multidisciplinary team including physiotherapists, occupational therapists, speech therapists, and clinical psychologists.

  Pop-up definition: Failure to thrive (FTT) is a term used in healthcare to describe a condition in which a child, typically an infant or young child, is not growing or developing as expected for their age. [BC1]