Research Explained: Patient with a heterozygous pathogenic variant in CSNK2A1 gene: A new case to update the Okur–Chung neurodevelopmental syndrome (2024)

Authors: Albin Blanc, Céline Bonnet, Marion Wandzel, Virginie Roth, Yannis Duffourd, Hanna Safraou, Bruno Leheup, Florence Muller, Julie D Colne, François Feillet, Emmanuelle Schmitt, Matheus Castro, Jullian Savatt, Adriano Burcheri, Christophe Nemos, Christophe Philippe, Laëtitia Lambert 

Publication Date: May 6, 2024

Research Explained By: Gabrielle Rushing, PhD, Science Program Director

Research Simplified Summary:

This publication describes a 7-year-old male in France with a CSNK2A1 Arg47Gln (R47Q) variant, known to cause Okur-Chung Neurodevelopmental Syndrome (OCNDS). The authors describe novel features that are potentially associated with OCNDS, including:

1. Clubfeet (a common birth defect affecting muscles and bones in the feet causing the foot to point down and turn in)
2. Exotropia (a type of strabismus, or eye misalignment where one eye deviates outward), and
3. Peg lateral incisor teeth (a condition where the second tooth on either side of the front teeth does not develop correctly and is small, pointed, and looks like a cone

The authors propose that this case report may extend the phenotypic spectrum (which symptoms present) in OCNDS. Strabismus (eye misalignment) has been mentioned as a rare symptom in a previous Gene Review publication by Dr. Okur and Dr. Chung. Other dental malformations have recently been described in OCNDS including long incisors, cracked teeth, missing enamel, small teeth, and fused teeth.

One limitation of this case study is that the child inherited a duplication (a type of mutation that involves the production of one or more copies of a gene or region of a chromosome) of genetic material on a different chromosome than CSNK2A1, but this duplication is currently classified as a variant of uncertain significance, meaning that we don’t have enough evidence to tell if this DNA change contributes to the symptoms that present in the child. Further research is needed to determine if specific symptoms correlate with specific changes in the CSNK2A1 gene and if the symptoms reported in this case study are more prevalent in the OCNDS population.