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. 2015;7(1):2.
doi: 10.1186/1866-1955-7-2. Epub 2015 Jan 5.

There is variability in the attainment of developmental milestones in the CDKL5 disorder

Stephanie Fehr  1 , Helen Leonard  1 , Gladys Ho  2 , Simon Williams  3 , Nick de Klerk  1 , David Forbes  4 , John Christodoulou  5 , Jenny Downs  6
Affiliations

There is variability in the attainment of developmental milestones in the CDKL5 disorder

Stephanie Fehr et al. J Neurodev Disord. 2015.

Abstract

Background: Individuals with the CDKL5 disorder have been described as having severely impaired development. A few individuals have been reported having attained more milestones including walking and running. Our aim was to investigate variation in attainment of developmental milestones and associations with underlying genotype.

Methods: Data was sourced from the International CDKL5 Disorder Database, and individuals were included if they had a pathogenic or probably pathogenic CDKL5 mutation and information on early development. Kaplan-Meier time-to-event analyses investigated the occurrence of developmental milestones. Mutations were grouped by their structural/functional consequence, and Cox regression was used to investigate the relationship between genotype and milestone attainment.

Results: The study included 109 females and 18 males. By 5 years of age, only 75% of the females had attained independent sitting and 25% independent walking whilst a quarter of the males could sit independently by 1 year 3 months. Only one boy could walk independently. No clear relationship between mutation group and milestone attainment was present, although females with a late truncating mutation attained the most milestones.

Conclusion: Attainment of developmental milestones is severely impaired in the CDKL5 disorder, with the majority who did attain skills attaining them at a late age. It appears as though males are more severely impaired than the females. Larger studies are needed to further investigate the role of genotype on clinical variability.

Keywords: CDKL5 disorder; Developmental disabilities; Early infantile epileptic encephalopathy; Epileptic encephalopathy.

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Figures

Figure 1
Figure 1
Schematic representation of the CDKL5 protein and our mutational grouping. Legend: The catalytic region is shown in light grey and the C-terminal region in white. Modified from ‘What We Know and Would Like to Know about CDKL5 and its Involvement in Epileptic Encephalopathy’ [17]. TEY motif Thr-Glu-Tyr motif, NLS 1 and NLS 2 nuclear localisation signals 1 and 2, NES nuclear export signal.
Figure 2
Figure 2
The proportion of females and males with the CDKL5 disorder who attained developmental milestones by various ages. Legend: A: independent sitting, B: independent standing, C: independent walking, D: raking grasp, E: pincer grip, F: babble, G: single words.
Figure 3
Figure 3
The influence of mutation type of the proportion of females with the CDKL5 disorder who attained developmental milestones by various ages. Legend: A: independent sitting, B: independent standing, C: independent walking, D: raking grasp, E: pincer grip, F: babble, G: single words.
See this image and copyright information in PMC

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