CDKL5 deficiency disorder (CDD)

CDLK5 deficiency (CDD)

• was first identified as a cause of human disease in 2004 (1)
  
• is a complex clinical condition resulting from non-functional or absent CDKL5 protein, a serine–threonine kinase pivotal for neural maturation and synaptogenesis (2)
  
• CDD was initially considered a variant of Rett syndrome - but is now recognised as an independent disorder and classified as a developmental epileptic encephalopathy
  
• is an X-linked disorder and exhibits a prevalence four times greater in females, indicating that germline mutations in males during the fetal period are not compatible with life (2)
  
• is an ultra-rare disorder with an estimated incidence of 2·36 per 100 000 livebirths (1)
  
• characterised by early-onset (generally within the first 2 months of life) seizures that are usually refractory to polypharmacy
  
• development is severely impaired in patients with CDD, with only a quarter of girls and a smaller proportion of boys achieving independent walking; however, there is clinical variability, which is probably genetically determined (1)
  
• gastrointestinal, sleep, and musculoskeletal problems are common in CDD, as in other developmental epileptic encephalopathies, but the prevalence of cerebral visual impairment appears higher in CDD (1)

Reference:

1. Leonard H et al. CDKL5 deficiency disorder: clinical features, diagnosis, and management. Lancet Neurol. 2022 Jun;21(6):563-576.
2. Dell'Isola B et al. CDKL5 deficiency-related neurodevelopmental disorders: a multi-center cohort study in Italy. J Neurol. 2024 Aug;271(8):5368-5377.