A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5
Hirotomo Saitsu1, Hitoshi Osaka, Kiyomi Nishiyama
1Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. hsaitsu@yokohama-cu.ac.jp
Insights
Cyclin-dependent kinase-like 5 (CDKL5) gene deletions in girls can cause early-onset epileptic encephalopathy and Rett syndrome-like features. Genetic testing for CDKL5 deletions is recommended for affected Japanese girls.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Cyclin-dependent kinase-like 5 (CDKL5) gene mutations are linked to early-onset epileptic encephalopathy and Rett syndrome-like features in female patients.
- CDKL5-related disorders present with severe developmental delay, intractable seizures, and hypotonia.
Observation:
- A case study of a Japanese girl with early-onset epileptic encephalopathy, hypotonia, and developmental regression.
- The patient exhibited generalized tonic seizures and stimulus-induced myoclonus.
- Brain MRI revealed cerebral atrophy without structural anomalies; EEG showed diffuse polyspike and wave discharges.
Findings:
- Genomic microarray identified a microdeletion at Xp22.13.
- Quantitative PCR and breakpoint-specific PCR confirmed a de novo 137-kb deletion encompassing CDKL5, RS1, and PPEF1 genes.
- This deletion involved critical exons of the CDKL5 gene.
Implications:
- This case suggests CDKL5 deletions are implicated in Japanese patients with similar clinical presentations.
- Genetic testing for CDKL5, including deletion analysis, should be considered for girls with early-onset epileptic encephalopathy and Rett syndrome-like features.
- Early and accurate genetic diagnosis is crucial for appropriate management and genetic counseling.
Abstract:
Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features.
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