Research Explained: Extending the phenotype associated with the CSNK2A1-related Okur-Chung Syndrome – A clinical study of 11 individuals

Authors: Ceris I. Owen, Ramsay Bowden, Michael J. Parker, Jo Patterson, Joan Patterson, Sue Price, Ajoy Sarkar, Bruce Castle, Charulatha Deshpande, Miranda Splitt, Neeti Ghali, John Dean, Andrew J. Green, Charlene Crosby, Deciphering Developmental Disorders Study, and Katrina Tatton-Brown.

Publication Date: December 16th, 2017

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

Link to article: https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.38610

Research Explained Summary:

Patients with a developmental disorder identified by the Deciphering Developmental Disorders Study at the Wellcome Trust Sanger Institute were genetically sequenced, and 11 were identified to have mutations in the CSNK2A1 gene, causative of OCNDS. Eight distinct mutations were found in these 11 patients, which were not found in the general population, the rest of their developmental disorder cohort, or the parents of the individual children. This indicates that these mutations are de novo, meaning that these mutations weren’t inherited from the child’s parents, but instead occur only in the children.

Clinical features were analyzed, with the most frequently reported being intellectual disability at varying levels. Overall, the average amount of time it took for patients to start sitting without help, walking, or speaking were 11.5 months, 30.5 months, and 44 months respectively, which is significantly delayed from typical development. Other commonly observed manifestations included muscle weakness (hypotonia), behavioral issues, swallowing difficulties, short stature, small head/brain size (microcephaly) and heart defects. Although previous studies have reported characteristic facial features, this study indicated that while there were some recurrent features, these were not significantly indicative of OCNDS.

Together with previous work, this study increases both the number of known OCNDS cases and validates symptoms found in previous cohorts and individuals. Particularly, this study indicates that cardiac dysfunction should be evaluated in OCNDS patients, a trait which hadn’t been seen before, further highlighting the differences across individuals with OCNDS.