Understanding
Okur-Chung Neurodevelopmental Syndrome
Research Explained: Motor phenotypes associated with genetic neurodevelopmental disorders
Authors: Alexandra Santana Almansa, LeeAnne Green Snyder, Wendy K. Chung, Jennifer M. Bain, and Siddharth Srivastava
Written By: Tierney Baum, PhD, Strategic R&D Consultant
Edited by: Gabrielle Rushing, PhD, Chief Scientific Officer, CSNK2A1 Foundation
This recent publication focuses on characterizing motor disturbances in patients with neurodevelopmental disorders (NDDs) by analyzing available data in the Simons Searchlight database. Researchers in this study were interested in determining if certain genetic disorders were associated with a more severely affected motor presentation in patients. Both CSNK2A1 and the sister gene, CSNK2B, were included in the study.
Simons Searchlight is an online international research program with a natural history database, biorepository, and resource network for over 175 rare genetic neurodevelopmental disorders.
Simons Searchlight is a project supported by the Simons Foundation, through the Simons Foundation Autism Research Initiative (SFARI).
Summary of Results
Motor Milestone: Sitting Unsupported
- Records from 777 individuals showed the average age of sitting unsupported at 11.4 months
- Individuals with CSNK2A1 mutations had an average age of sitting of 9.9 months unsupported and individuals with CSNK2B mutations had an average age of sitting of 8.2 months
Motor Milestone: Walking Independently
- Records from 638 individuals showed the average age of walking independently at 25.4 months
- Individuals with CSNK2A1 mutations had an average age of walking independently at 30.6 months and individuals with CSNK2B mutations h an average age of walking independently at 18 months
- One CSNK2A1 patient had an age of walking reported at ~240 months (20 years)
Tone Abnormalities
- 696 individuals were reported to have tone abnormalities with 83% reporting hypotonia, 16% hypertonia, 10% cerebral palsy (CP), and 3% spastic CP
- Researchers note that of all the genetic neurodevelopmental disorders reported, CTNNB1 and DYRK1A-related disorders had a notably high prevalence of motor disturbances. Outside of these two disorders there was generally a low prevalence of reported CP among other NDDs (~10%)
- 30 CSNK2A1 patients self-reported tone abnormalities.
- Out of these 30, only 1 CSNK2A1 patient was reported to have hypertonia and 2 out of 30 (~7%) were reported to have cerebral palsy.
Definitions
Hypotonia - low muscle tone or muscle weakness
Hypertonia - high muscle tone so that limbs may be stiff and difficult to move
Cerebral Palsy - a group of neurological disorders that effect the ability to move, maintain balance, and control muscles
Spastic Cerebral Palsy - a type of cerebral palsy that causes increased muscle tone, causing stiff muscles and muscle spasms
The charts below show different numbers in the columns:
Column 1: descriptive (gene and milestone name)
Column 2: the total number of patients included in the study for CSNK2A1 (42) and CSNK2B (8)
Column 3: the average age in months of the patients in the study
Column 4: the average age of achievement of listed milestone (e.g., sitting or walking)
Column 5: the minimum or lowest age reported in the study for listed milestone
Column 6: the maximum or highest age reported in the study for listed milestone (for patients who reported reaching the milestone)
Column 7: percentage of patients that have not yet reached the milestone
| CSNK2A1 | Number of patients | Age at evaluation in months - average | Achievement age of milestones in months – average | Achievement age of milestones in months – min | Achievement age of milestones in months - max | % not yet* |
|---|---|---|---|---|---|---|
| Sitting | 42 | 90.5 | 9.9 | 4 | 24 | 4.8 (2/42) |
| Walking | 42 | 90.5 | 30.6 | 14 | 240 | 4.9 (2/42) |
| CSNK2B | Number of patients | Age at evaluation in months - average | Achievement age of milestones in months – average | Achievement age of milestones in months – min | Achievement age of milestones in months - max |
|---|---|---|---|---|---|
| Sitting | 8 | 62.1 | 8.2 | 5 | 13 |
| Walking | 8 | 62.1 | 18 | 13 | 23 |
*All 8 CSNK2B patients in the study achieved the milestones of sitting and walking whereas 2 CSNK2A1 patients in the study had not yet achieved the milestones at the time of analysis.
What does this mean for individuals with OCNDS?
This study highlights key insights into motor development and tone abnormalities in individuals with CSNK2A1 mutations compared to other neurodevelopmental disorders (NDDs). By better understanding these patterns, families and clinicians can anticipate challenges and implement targeted strategies to optimize developmental outcomes for individuals with OCNDS.
Motor Milestones
- Sitting Unsupported: Individuals with CSNK2A1 mutations typically achieve sitting unsupported at an average of 9.9 months, which is slightly earlier than the general average for individuals with NDDs (11.4 months). However, 4.8% of individuals with CSNK2A1 mutations had not yet reached this milestone at the time of the study.
- Walking Independently: Walking independently occurred later, at an average age of 30.6 months, compared to the general average for NDDs (25.4 months). Notably, 4.9% had not achieved this milestone, with one individual reporting a walking age as late as ~240 months.
Tone Abnormalities
- Among individuals with CSNK2A1, tone abnormalities were reported in 30 patients:
- Hypotonia (low muscle tone) was the most common.
- Only 7% reported cerebral palsy, reflecting a relatively low prevalence compared to disorders like CTNNB1 and DYRK1A.
Implications
- Developmental Variation: Motor development in individuals with CSNK2A1 mutations shows significant variation. While many achieve milestones on time, others may face delays, underscoring the need for tailored early interventions and physical therapies.
- Low Risk of Severe Motor Impairment: A lower prevalence of severe motor impairments, such as CP, is encouraging, though hypotonia remains a common concern.
- Individualized Care: These findings highlight the importance of individualized developmental monitoring and support for motor skills in individuals with CSNK2A1 mutations.