Myoclonic encephalopathy in the CDKL5 gene mutation

Buoni, Sabrina; Zannolli, Raffaella; Colamaria, V.; Macucci, Francesca; Bartolo, Rosanna Maria Di; Corbini, Letizia; Orsi, A; Zappella, Michele; Hayek, Joussef

doi:10.1016/j.clinph.2005.09.008

Cited by 41 publications

(51 citation statements)

References 10 publications

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“…Bahi-Buisson et al 8 described 12 individuals with an initially normal background EEG activity and subsequent deterioration occurring between 6 months and 3 years of life. Buoni et al 7 described an EEG pattern mainly with sporadic focal abnormalities in three infants in their first year of life, which they judged as not suggestive of an epileptic encephalopathy. Archer et al 9 reported that Fp2-F4 F4-C4 C4-P4 P4-O2 Fp2-F8 F8-T4 T4-T6 T6-O2 Fp1-F3 F3-C3 C3-P3 P3-O1 Fp1-F7 F7-T3 T3-T5 T5- background EEG in the first year of life was normal for three individuals and very slow with superimposed multifocal spikes for another three.…”

Section: Discussionmentioning

confidence: 99%

“…After a seemingly normal early development, intractable seizures occur at around 3 to 4 months of life, followed by progressive evidence of severely impaired developmental skills and communication. 2 Reported electroclinical descriptions are diverse, including X-linked infantile spasms, 6 myoclonic encephalopathy, 7 and a threestage epileptic encephalopathy. 8 We focused our analysis on the electroclinical features in the first year of life in order to determine whether an early-onset pattern is at all recognizable.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5] Clinical and electroencephalographic (EEG) studies have identified various features of epileptic encephalopathy that are encountered in most individuals with the disorder, at least at some point during development, including infantile spasms 6 and a form of myoclonic encephalopathy. 7 No study has specifically addressed electroclinical features in the first year of life. This is important because early detection of specific patterns would help more targeted planning of molecular genetic testing and, consequently, differential diagnosis.…”

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CDKL5 gene‐related epileptic encephalopathy: electroclinical findings in the first year of life

Melani

Mei

Pisano

et al. 2011

Develop Med Child Neuro

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ACTH Adrenocorticotropic hormoneAIM Cyclin-dependent kinase-like 5 (CDKL5) gene abnormalities cause an early-onset epileptic encephalopathy. We performed video-electroencephalography (video-EEG) monitoring early in the course of CDKL5-related epileptic encephalopathy in order to examine the early electroclinical characteristics of the condition.METHOD We used video-EEG to monitor six infants (five females, one male) with CDKL5-related epileptic encephalopathy (five mutations; one deletion), at ages 45 days to 12 months and followed them up to the ages of 14 months to 5 years (mean age 23mo). We focused our analysis on the first year of life. The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative for CDKL5 mutations and deletions.RESULTS One infant exhibited normal background activity, three exhibited moderate slowing, and two exhibited a suppression burst pattern. Two participants had epileptic spasms and four had a stereotyped complex seizure pattern, which we defined as a 'prolonged' generalized tonic-clonic event consisting of a tonic-tonic ⁄ vibratory contraction, followed by a clonic phase with series of spasms, gradually translating into repetitive distal myoclonic jerks. Seizure duration ranged from 2 to 4 minutes. The EEG correlate of each clinical phase included an initial electrodecremental event (tonic vibratory phase), irregular series of sharp waves and spike slow waves (clonic phase with series of spasms), and bilateral rhythmic sharp waves (time locked with myoclonus).INTERPRETATION Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual electroclinical pattern of 'prolonged' generalized tonic-clonic seizures.Mutations of or deletions in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) have been shown to cause an epileptic encephalopathy with early-onset severe neurological impairment and intractable seizures.1 The condition has mainly been reported in females, 2 with only six affected males having been described. [3][4][5] Clinical and electroencephalographic (EEG) studies have identified various features of epileptic encephalopathy that are encountered in most individuals with the disorder, at least at some point during development, including infantile spasms 6 and a form of myoclonic encephalopathy.7 No study has specifically addressed electroclinical features in the first year of life. This is important because early detection of specific patterns would help more targeted planning of molecular genetic testing and, consequently, differential diagnosis.We investigated six infants, five of whom harboured CDKL5 mutations and one of whom had a deletion, and evaluated video-EEG recordings in the first year of life. We describe their electroclinical features, including a highly characteristic ictal pattern. METHODWe studied six consecutive individuals (five females, one male; age range 45d-12mo), now aged from 14 months to 5 years (mean age 23....

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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CDKL5 gene‐related epileptic encephalopathy: electroclinical findings in the first year of life

Melani

Mei

Pisano

et al. 2011

Develop Med Child Neuro

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“…CDKL5 mutations also cause ISSX [98], a form of myoclonic encephalopathy [99], and severe encephalopathy with refractory seizures (Table 1) [100]. Mutations in CDKL5 are found mainly in girls, suggesting gestational lethality in boys [101].…”

Section: Cyclin-dependent Kinase-likementioning

confidence: 99%

Genetic Epilepsy Syndromes Without Structural Brain Abnormalities: Clinical Features and Experimental Models

2014

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Research in genetics of epilepsy represents an area of great interest both for clinical purposes and for understanding the basic mechanisms of epilepsy. Most mutations in epilepsies without structural brain abnormalities have been identified in ion channel genes, but an increasing number of genes involved in a diversity of functional and developmental processes are being recognized through whole exome or genome sequencing. Targeted molecular diagnosis is now available for different forms of epilepsy. The identification of epileptogenic mutations in patients before epilepsy onset and the possibility of developing therapeutic strategies tested in experimental models may facilitate experimental approaches that prevent epilepsy or decrease its severity. Functional analysis is essential for better understanding pathogenic mechanisms and gene interactions. In vitro experimental systems are either cells that usually do not express the protein of interest or neurons in primary cultures. In vivo/ex vivo systems are organisms or preparations obtained from them (e.g., brain slices), which should better model the complexity of brain circuits and actual pathophysiological conditions. Neurons differentiated from induced pluripotent stem cells generated from the skin fibroblasts of patients have recently allowed the study of mutations in human neurons having the genetic background of a given patient. However, there is remarkable complexity underlying epileptogenesis in the clinical dimension, as reflected by the fact that experimental models have not provided yet results having clinical translation and that, with a few exceptions concerning rare conditions, no new curative treatment has emerged from any genetic finding in epilepsy.

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“…Axial hypotonia, severe developmental delay and autistic spectrum disorder are also frequently found in patients with these mutations 1 . Different epileptic manifestations were described in patients with mutations in the CDKL5 gene, including seizures with onset at the first six months of life, infantile spasms and myoclonic epilepsy 1,2 . In 2007, the two first Brazilian patients with Rett syndrome and mutations in the MeCP2 gene were reported 3 .…”

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Epileptic encephalopathy and atypical Rett syndrome with mutations in CDKL5: clinical and molecular characterization of two Brazilian patients

Ermel

Carneiro

Souza

et al. 2013

Arq. Neuro-Psiquiatr.

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Myoclonic encephalopathy in the CDKL5 gene mutation

Cited by 41 publications

References 10 publications

CDKL5 gene‐related epileptic encephalopathy: electroclinical findings in the first year of life

CDKL5 gene‐related epileptic encephalopathy: electroclinical findings in the first year of life

Genetic Epilepsy Syndromes Without Structural Brain Abnormalities: Clinical Features and Experimental Models

Epileptic encephalopathy and atypical Rett syndrome with mutations in CDKL5: clinical and molecular characterization of two Brazilian patients

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