Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a severe X-linked neurodevelopmental encephalopathy caused by mutations in the <i>CDKL5</i> gene and characterized by early-onset epilepsy and intellectual and motor impairments.
Our findings suggest that CDKL5 mutations likely play a direct role in psychomotor development, whereas epilepsy is one of the clinical features associated with this complex disorder.
Our aim was to describe diaper changing-induced reflex seizures as one of the presenting features in a case of CDKL5-related epilepsy, providing video-EEG documentation and focusing discussion on hyperexcitability determined by the disease.
The purpose of this study was to evaluate the frequency of mosaicism detected by next-generation sequencing in genes associated with epilepsy-related neurodevelopmental disorders.MethodsWe conducted a retrospective analysis of 893 probands with epilepsy who had a multigene epilepsy panel or whole-exome sequencing performed in a clinical diagnostic laboratory and were positive for a pathogenic or likely pathogenic variant in one of nine genes (CDKL5, GABRA1, GABRG2, GRIN2B, KCNQ2, MECP2, PCDH19, SCN1A, or SCN2A).
The consequent misexpression of the CDKL5 protein in the nervous system leads to a severe phenotype characterized by intellectual disability, motor impairment, visual deficits and early-onset epilepsy.
The systematic search took place in February/2017 and updated in December/2017 using the keywords "epilepsy" or "Dravet" or "Lennox-Gastaut" or "CDKL5" combined with "Cannabis," "cannabinoid," "cannabidiol," or "CBD" resulting in 199 papers.
We report on two patients, a boy and a girl, with EIEE2 that present with early onset epilepsy, hypotonia, severe intellectual disability, and poor eye contact.
Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features.
In order to clarify the CDKL5 genotype-phenotype correlations in Chinese patients, CDKL5 mutational screening in cases with early-onset epileptic encephalopathies and RTT without MECP2 mutation were performed.
Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys.
Four probands had de novo mutations in genes previously shown to harbor heterozygous mutations in patients with severe, early onset epilepsies (two in SCN1A, and one each in CDKL5 and EEF1A2).
This study demonstrated the importance of CDKL5 mutations as etiological factors in neurodevelopmental disorders, and indicated that a thorough analysis of the CDKL5 gene sequence and its rearrangements should be considered in females with Rett syndrome-like phenotypes, severe encephalopathy and epilepsy with onset before 5 months of age.
It is now clearly emerging that epilepsy has distinctive characteristics in typical Rett syndrome and in the different syndromes caused by CDKL5 and FOXG1 gene alterations.
The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative forCDKL5 mutations and deletions.
The severity of epilepsy associated with CDKL5 mutations was recently shown to correlate with the type of CDKL5 mutations and epilepsy was identified to involve three distinct sequential stages.
Atypical RS with severe early-onset encephalopathy and therapy-resistant epilepsy can be due to mutations in the CDKL5 (Cyclin-Dependent Kinase-like 5) gene in Xp22.