Cerebral Visual Impairment in CDKL5 Deficiency Disorder Correlates With Developmental Achievement

Abstract

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder is a rare neurodevelopmental disorder characterized by infantile-onset refractory epilepsy, profound developmental delays, and cerebral visual impairment. Although there is evidence that the presence of cerebral visual impairment in CDKL5 deficiency disorder is common, the potential impact of cerebral visual impairment severity on developmental attainment has not been explored directly. Focusing on a cohort of 46 children with CDKL5 deficiency disorder, examination features indicative of cerebral visual impairment were quantified and compared to developmental achievement. The derived cerebral visual impairment severity score was inversely correlated with developmental attainment, bolstering the supposition that cerebral visual impairment severity may provide a useful early biomarker of disease severity and prognosis. This study demonstrates the utility of a cerebral visual impairment score to better capture the range of cerebral visual impairment severity in the CDKL5 deficiency disorder population and further elucidates the interaction between cerebral visual impairment and developmental outcomes.

Keywords: CDKL5 deficicency disorder; Cerebral vision impairment; developmental and epileptic encephalopathy; developmental outcome.

Figure 1.

CVI Severity Score: List of CVI Variables and their Corresponding ‘Points.’ The Variables, when Present on Exam, are Summed According to their Value. Minimum Score Possible = 0; Maximum Points Possible = 7.

Figure 2.

7-Point Development Scale: Variables included in the 7-Point Developmental Scale, Subdivided into Three Domains (i.e., Gross Motor, Hand Function, Expressive Communication). The Variables within each Domain are Considered Ordinal, such that the Presence of more Advanced Milestones Assume Preceding Milestones if not otherwise Indicated on History. Minimum Score Possible = 0; Maximum Points Possible = 7.

Figure 3.

16-Point Development Scale: Variables Included in the Expanded 16-point Developmental Scale, Subdivided into four Domains (i.e., Gross Motor, Hand Function, Expressive Communication, Social/Cognitive). Expressive Communication was Further Divided into Verbal and Nonverbal Communication. Each Domain has a Maximum of four Possible Points. Minimum Score Possible = 0; Maximum Points Possible = 16.

Figure 4.

Scatterplot of CVI scores vs developmental scores. Adjusted R-Square and prediction line based on multiple linear regression model. A jitter option was used to see overlapping points.