CDKL5 Deficiency Disorder (CDD)-Rare Presentation in Male

Abstract

CDKL5 deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the X-linked cyclin-dependent kinase 5 (CDKL5) gene. This rare disorder occurs more frequently in females than in males. The incidence is estimated to be approximately 1: 40,000-60,000 live births. So far, 50 cases have been described in boys. The clinical course in males tends to be more severe and is often associated with death in the first or second decade of life. The authors present an unreported 2.5-year-old male patient with drug-resistant epilepsy who was diagnosed with a de novo mutation in the CDKL5 gene. First seizures developed in the fifth week of life and have progressed steadily since then. The child's psychomotor development was strongly delayed, and generalized hypotonia was noticed since birth. Brain MRI showed areas of incomplete myelination, posterior narrowing of the corpus callosum, a pineal cyst of up to 3 mm, and open islet lids. Intensive antiseizure medications (ASMs), a ketogenic diet, and steroid therapy were not successful. Short-term improvement was achieved with the implantation of a vagal nerve stimulator (VNS). Due to the progressive course of the disease, the boy requires frequent modification of ASMs.

Keywords: CDKL5 deficiency disorder; children; epileptic encephalopathy; refractory epilepsy.

Figure 1

(a–c) Brain MRI in transverse planes: (a) normal in T1; (b,c) unfished myelinisation in peritrigonal white matter in (b) T2; (c) T2 FLAIR.

Figure 2

(a–c) Brain MRI, axial (a) T2 FLAIR (b) T2, coronal (T2) unfinished myelinisation of white matter surrounding occipital horns.

Figure 3

(a–c) Brain MRI in advanced sequences: (a) DWI diffusion weighted imaging; (b) ADC map—apparent diffusion coefficient map—areas of prolonged diffusion in peritrigonal white matter regions corresponding to unfinished myelinisation, (c) FA—fractional anisotropy sequence—symmetrical image of fibers of both hemispheres.