CDKL5-associated developmental and epileptic encephalopathy: A long-term, longitudinal electroclinical study of 22 cases

Darra, Francesca; Monchelato, Manuela; Loos, Mariana; Juanes, Matías; Bernardina, Bernardo Dalla; Valenzuela, Gabriela Reyes; Gallo, Adolfo; Caraballo, Roberto

doi:10.1016/j.eplepsyres.2023.107098

Cited by 4 publications

(1 citation statement)

References 37 publications

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“…Long-term video/EEG monitoring recorded seizures appearing as tonic seizures followed by bursts of periodic myoclonias (Figure 1). The EEG pattern promptly suggested the etiological diagnosis of a CDKL5 encephalopathy, as is typical of this type of developmental disorder [20]. Subsequently, other seizures occurred in the following months, including focal seizures and hypermotor seizures interspersed with tonic seizures, also described in CDKL5 encephalopathy and suggestive of this clinical entity.…”

Section: Case Reportmentioning

confidence: 80%

A Case of CDKL5 Deficiency Due to an X Chromosome Pericentric Inversion: Delineation of Structural Rearrangements as an Overlooked Recurrent Pathological Mechanism

Lombardo,

Sinibaldi,

Genovese

et al. 2024

IJMS

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CDKL5 deficiency disorder (CDD) is an X-linked dominant epileptic encephalopathy, characterized by early-onset and drug-resistant seizures, psychomotor delay, and slight facial features. Genomic variants inactivating CDKL5 or impairing its protein product kinase activity have been reported, making next-generation sequencing (NGS) and chromosomal microarray analysis (CMA) the standard diagnostic tests. We report a suspicious case of CDD in a female child who tested negative upon NGS and CMA and harbored an X chromosome de novo pericentric inversion. The use of recently developed genomic techniques (optical genome mapping and whole-genome sequencing) allowed us to finely characterize the breakpoints, with one of them interrupting CDKL5 at intron 1. This is the fifth case of CDD reported in the scientific literature harboring a structural rearrangement on the X chromosome, providing evidence for the hypothesis that this type of anomaly can represent a recurrent pathogenic mechanism, whose frequency is likely underestimated, with it being overlooked by standard techniques. The identification of the molecular etiology of the disorder is extremely important in evaluating the pathological outcome and to better investigate the mechanisms associated with drug resistance, paving the way for the development of specific therapies. Karyotype and genomic techniques should be considered in all cases presenting with CDD without molecular confirmation.

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Section: Case Reportmentioning

confidence: 80%

A Case of CDKL5 Deficiency Due to an X Chromosome Pericentric Inversion: Delineation of Structural Rearrangements as an Overlooked Recurrent Pathological Mechanism

Lombardo,

Sinibaldi,

Genovese

et al. 2024

IJMS

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Clinical phenotype and genetic characteristics of SZT2 related diseases: A case report and literature review

Zhang,

Han,

Yang

et al. 2024

Seizure: European Journal of Epilepsy

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CDKL5 deficiency disorder: progressive brain atrophy may be part of the syndrome

et al. 2023

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The clinical phenotype of Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) has been delineated but neuroimaging features have not been systematically analyzed. We studied brain magnetic resonance imaging (MRI) scans in a cohort of CDD patients and reviewed age at seizure onset, seizure semiology, head circumference. Thirty-five brain MRI from 22 unrelated patients were included. The median age at study entry was 13.4 years. In 14/22 patients (85.7%), MRI in the first year of life was unremarkable in all but two. In 11/22, we performed MRI after 24 months of age (range 2.5–23 years). In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain (−17.7%, P-value = 0.014), including both white matter (−25.7%, P-value = 0.005) and cortical gray matter (−9.1%, P-value = 0.098), with a reduction of surface area (−18.0%, P-value = 0.032), mainly involving the temporal regions, correlated with the head circumference (ρ = 0.79, P-value = 0.109). Both the qualitative structural assessment and the quantitative analysis detected brain volume reduction involving the gray and white matter. These neuroimaging findings may be related to either progressive changes due to CDD pathogenesis, or to the extreme severity of epilepsy, or both. Larger prospective studies are needed to clarify the bases for the structural changes we observed.

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CDKL5-associated developmental and epileptic encephalopathy: A long-term, longitudinal electroclinical study of 22 cases

Cited by 4 publications

References 37 publications

A Case of CDKL5 Deficiency Due to an X Chromosome Pericentric Inversion: Delineation of Structural Rearrangements as an Overlooked Recurrent Pathological Mechanism

A Case of CDKL5 Deficiency Due to an X Chromosome Pericentric Inversion: Delineation of Structural Rearrangements as an Overlooked Recurrent Pathological Mechanism

Clinical phenotype and genetic characteristics of SZT2 related diseases: A case report and literature review

CDKL5 deficiency disorder: progressive brain atrophy may be part of the syndrome

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