CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature

Lilles, Stella; Talvik, Inga; Noormets, Klari; Vaher, Ulvi; Õunap, Katrin; Reimand, Tiia; Sander, Valentin; Ilves, Pilvi; Talvik, Tiina

doi:10.1055/s-0036-1586730

Cited by 12 publications

(2 citation statements)

References 20 publications

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“…55 To further confirm this figure, in literature from 2004 to 2018, approximately 200 new cases of CDKL5-related disorders have been described, of which 40 are males. [56][57][58][59][60][61] Furthermore, clinical severity of the CDKL5 disease for both genders has been described as very similar, most often overlapping. Therefore, these studies suggest that, contrary to the Rett-syndrome, CDKL5 disorders are not exclusive to the female sex, and CDKL5 testing should be considered independently of the gender.…”

Section: Clinical Presentationsmentioning

confidence: 99%

CDKL5 Gene: Beyond Rett Syndrome

Ciccia

Scalia

Venti

et al. 2021

Journal of Pediatric Neurology

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CDKL5 is a gene located in the X-chromosome (Xp22) encoding a serine/threonine kinase involved in various signaling pathways, implicated in cell proliferation, axon development, dendrite growth, synapse formation, and maintenance. Mutations occurring in this gene have been associated with drug-resistant early-onset epilepsy, with multiple seizures type, and deep cognitive and motor development delay with poor or absent speech, ataxic gait or inability to walk, hand stereotypies and in a few cases decrement of head growth. Many aspects remain unclear about the CDKL5 deficiency disorders, research will be fundamental to better understand the pathogenesis of neurological damage and consequently developed more targeted and profitable therapies, as there is not, at the present, a gene-based treatment and the seizures are in most of the cases drug resistant. In this article, we summarize the actual knowledge about CDKL5 gene function and mostly the consequence given by its dysfunction, also examining the possible therapeutic approaches.

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Section: Clinical Presentationsmentioning

confidence: 99%

CDKL5 Gene: Beyond Rett Syndrome

Ciccia

Scalia

Venti

et al. 2021

Journal of Pediatric Neurology

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“…[10], выраженность клинических проявлений у лиц обоих полов одинакова, в то время как данные, полученные S. Lilles и соавт. [11], свидетельствуют в пользу большей выраженности клинических проявлений у пациентов мужского пола.…”

Section: Introductionunclassified

Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations

Дадали

Акимова

Коновалов

et al. 2020

Rus. ž. det. nevrol.

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Early infantile epileptic encephalopathies (EIEE) are a group of disorders characterized by pharmacoresistant epileptic seizures manifesting in infancy and leading to psychomotor retardation. The most common genetic variant with X-linked dominant inheritance is type 2 EIEE associated with CDKL5 gene mutations. We evaluated the prevalence of this type of EIEE among Russian patients (n = 148) with epileptic seizures manifesting in infancy and analyzed their clinical and genetic characteristics. We performed exome sequencing for all patients; 15 (10 %) of them (aged between 2 months and 5 years) were found to have CDKL5 gene mutations and were, therefore, diagnosed with type 2 EIEE. The results of correlation analysis suggest that the severity of clinical manifestations of type 2 EIEE is largely determined by the location of mutations affecting the function of the protein encoded by this gene. This is important to ensure better understanding of type 2 EIEE etiology and predict it severity in patients with different allelic variants.

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The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures

Burgess

Wang

McTague

et al. 2019

Annals of Neurology

106

109

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Objective Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe developmental and epileptic encephalopathies. We delineate the genetic causes and genotype–phenotype correlations of a large EIMFS cohort. Methods Phenotypic and molecular data were analyzed on patients recruited through an international collaborative study. Results We ascertained 135 patients from 128 unrelated families. Ninety‐three of 135 (69%) had causative variants (42/55 previously reported) across 23 genes, including 9 novel EIMFS genes: de novo dominant GABRA1, GABRB1, ATP1A3; X‐linked CDKL5, PIGA; and recessive ITPA, AIMP1, KARS, WWOX. The most frequently implicated genes were KCNT1 (36/135, 27%) and SCN2A (10/135, 7%). Mosaicism occurred in 2 probands (SCN2A, GABRB3) and 3 unaffected mothers (KCNT1). Median age at seizure onset was 4 weeks, with earlier onset in the SCN2A, KCNQ2, and BRAT1 groups. Epileptic spasms occurred in 22% patients. A total of 127 patients had severe to profound developmental impairment. All but 7 patients had ongoing seizures. Additional features included microcephaly, movement disorders, spasticity, and scoliosis. Mortality occurred in 33% at median age 2 years 7 months. Interpretation We identified a genetic cause in 69% of patients with EIMFS. We highlight the genetic heterogeneity of EIMFS with 9 newly implicated genes, bringing the total number to 33. Mosaicism was observed in probands and parents, carrying critical implications for recurrence risk. EIMFS pathophysiology involves diverse molecular processes from gene and protein regulation to ion channel function and solute trafficking. ANN NEUROL 2019;86:821–831

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CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature

Cited by 12 publications

References 20 publications

CDKL5 Gene: Beyond Rett Syndrome

CDKL5 Gene: Beyond Rett Syndrome

Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations

The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures

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