title: There is variability in the attainment of developmental milestones in the CDKL5 disorder.
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.
  
  
  CONCLUSIONS
  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.
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia Australia.
authors: Stephanie
authors: S
authors: Fehr
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia Australia.
authors: Helen
authors: H
authors: Leonard
authors: Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, NSW Australia.
authors: Gladys
authors: G
authors: Ho
authors: Department of Neurology and Rehabilitation, Princess Margaret Hospital, Perth, Western Australia Australia.
authors: Simon
authors: S
authors: Williams
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia Australia.
authors: Nick
authors: N
authors: de Klerk
authors: School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia Australia.
authors: David
authors: D
authors: Forbes
authors: Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, NSW Australia ; Disciplines of Paediatrics & Child Health and Genetic Medicine, University of Sydney, Sydney, NSW Australia.
authors: John
authors: J
authors: Christodoulou
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia Australia ; School of Physiotherapy and Exercise Science, Curtin University, Perth, Western Australia Australia.
authors: Jenny
authors: J
authors: Downs
keywords: CDKL5 disorder; Developmental disabilities; Early infantile epileptic encephalopathy; Epileptic encephalopathy
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