Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review

Overview

Journal Pediatr Neurol

Specialties Neurology
Pediatrics

Date 2019 Apr 1

PMID 30928302

Citations 106

Authors

Heather E Olson

Scott T Demarest

Elia M Pestana-Knight

Lindsay C Swanson

Sumaiya Iqbal

Dennis Lal

Helen Leonard

J Helen Cross

Orrin Devinsky

Tim A Benke

Affiliations

Soon will be listed here.

Abstract

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene CDKL5. This unique disorder includes early infantile onset refractory epilepsy, hypotonia, developmental intellectual and motor disabilities, and cortical visual impairment. We review the clinical presentations and genetic variations in CDD based on a systematic literature review and experience in the CDKL5 Centers of Excellence. We propose minimum diagnostic criteria. Pathogenic variants include deletions, truncations, splice variants, and missense variants. Pathogenic missense variants occur exclusively within the kinase domain or affect splice sites. The CDKL5 protein is widely expressed in the brain, predominantly in neurons, with roles in cell proliferation, neuronal migration, axonal outgrowth, dendritic morphogenesis, and synapse development. The molecular biology of CDD is revealing opportunities in precision therapy, with phase 2 and 3 clinical trials underway or planned to assess disease specific and disease modifying treatments.

Citing Articles

Beneficial Antioxidant Effects of Coenzyme Q10 in In Vitro and In Vivo Models of CDKL5 Deficiency Disorder.

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PMID: 40076840 PMC: 11900000. DOI: 10.3390/ijms26052204.

A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations.

Feng X, Zhu Z, Wang H, Zhou H, Liu J, Shen Y Neurosci Bull. 2025; .

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Women With Genetic Epilepsies.

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The genetic landscape and classification of infantile epileptic spasms syndrome requiring surgery due to suspected focal brain malformations.

Coleman M, Wang M, Snell P, Lee W, DArcy C, Mignone C Brain Commun. 2025; 7(1):fcaf034.

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Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.

Song X, Xia Z, Martinez D, Xu B, Spritzer Z, Zhang Y Cell Rep Med. 2025; 6(2):101926.

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