Research Explained: A Dual Diagnosis of Okur–Chung Neurodevelopmental Syndrome and Becker Muscular Dystrophy

Research Explained: A Dual Diagnosis of Okur–Chung Neurodevelopmental Syndrome and Becker Muscular Dystrophy: Inquiry Into the Lower Limits of Neurodevelopmental Functioning Attributable to Muscular Dystrophy

Authors: Victoria Liu, Eva Hanson, Joshua W. Owens, Robert J. Hopkin, Amelle Shillington

Author: Gabrielle Rushing, PhD, CSNK2A1 Foundation Chief Scientific Officer

Edited by: Tierney Baum, PhD, Strategic R&D Consultant

Link to Publication: https://pmc.ncbi.nlm.nih.gov/articles/PMC11802274/

Research Explained Summary

A recent case study published in Brain and Behavior describes a 3-year-old male with global developmental delay, growth failure, and dysmorphic facial features. Initially, genetic testing identified a duplication within the DMD gene, typically associated with Becker Muscular Dystrophy (BMD). Muscular dystrophies are disorders that cause progressive weakness and degeneration of skeletal muscle. However, the child’s significant neurodevelopmental impairments exceeded what is usually observed in BMD, prompting further genetic analysis. Whole-exome sequencing revealed a heterozygous CSNK2A1 variant, c.593A>G (p. Lys198Arg also referred to as K198R), confirming a dual diagnosis of Okur–Chung Neurodevelopmental Syndrome (OCNDS) alongside BMD. 

OCNDS is an autosomal dominant disorder caused by pathogenic variants in CSNK2A1, which encodes the αlpha1 catalytic subunit of protein kinase CK2, an essential enzyme involved in neural development, regulating gene expression, and cell signaling. The identified K198R variant affects a key lysine residue known to be crucial for the stability and function of the CK2 protein. Changes to CK2’s protein function within humans caused by the K198R variant is currently not fully understood.

Researchers found that the patient’s IQ scores were significantly lower than typically found with only a BMD diagnosis, prompting further investigation into other contributing factors. They conclude that unexplained symptoms in similar patients should prompt further diagnostic workup. This case underscores the importance of considering dual diagnoses in patients with neuromuscular conditions who present with unexpected neurodevelopmental challenges. The combination of BMD and OCNDS in this patient highlights the need for comprehensive genetic testing when a single diagnosis does not fully explain the clinical presentation. The findings also contribute to the growing understanding of CSNK2A1 variants, emphasizing the necessity for further research into the molecular and functional consequences of specific mutations, including K198R, to refine genotype-phenotype correlations and improve clinical management.