Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations

Kurahashi, N.; Miyake, Noriko; Mizuno, Seiji; Koshimizu, Eriko; Kurahashi, Hirokazu; Yamada, Keitaro; Natsume, Jun; Aoki, Yusuke; Nakamura, Miho; Taniai, Hiroko; Maki, Yuki; Abe-Hatano, Chihiro; Matsumoto, Naomichi; Maruyama, Koichi

doi:10.1016/j.braindev.2017.03.025

Cited by 20 publications

(23 citation statements)

References 31 publications

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“…21 Recent study reported that although seizure outcome is favorable in KS, 22 focal seizures in patient with KMT2D pathogenic variants do not respond immediately to medication. 23 Neurological work-up in our patient revealed a focal epilepsy involving the centrotemporal region of the left hemisphere, currently being treated only with valproic acid with excellent seizures control. 24 Most of the described KS cases reported normal brain MRI.…”

Section: Discussionmentioning

confidence: 69%

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome

et al. 2020

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Kabuki syndrome (KS) is a rare genetic condition with multiple congenital abnormalities and developmental delay. The cardinal manifestations of KS include characteristic facial features, intellectual disability, skeletal defects, dermatoglyphic abnormalities, and postnatal growth deficiencies. Cardiac and urological malformations are commonly present in patient with KS, as well as language deficits and immunological abnormalities. Here, we report a case of a child with an atypical form of KS, associated with macrodontia, corpus callosum dysmorphism, focal epilepsy responsive to antiepileptic treatment, and a novel KMT2D gene missense variant, c.2413C > T, never reported to date.

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Section: Discussionmentioning

confidence: 69%

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome

et al. 2020

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“…Childhood-onset epileptic encephalopathy (COEE) (Carvill et al, 2013;Suls et al, 2013) EHMT1 (Boissel et al, 2009;Rowles et al, 2012) KDM5C Lysine demethylase 5C Histone demethylase X-linked mental retardation (XLMR) (Poeta et al, 2013) KMT2D Lysine methyltransferase 2D Histone methyltransferase Kabuki syndrome (Kurahashi et al, 2017) MBD5 Methyl-binding domain 5 Methyl-DNA binding protein Intellectual disability, autosomal dominant 1 (MRD1); 2q23.1 microdeletion syndrome with seizures (Talkowski et al, 2011) MECP2 Methyl CpG binding protein 2…”

Section: Reader Of Histone Acetylation Marksmentioning

confidence: 99%

Epigenetics explained: a topic “primer” for the epilepsy community by the ILAE Genetics/Epigenetics Task Force

Kobow¹,

Reid²,

Vliet³

et al. 2020

Epileptic Disorders

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Epigenetics refers broadly to processes that influence medium to long‐term gene expression by changing the readability and accessibility of the genetic code. The Neurobiology Commission of the International League Against Epilepsy (ILAE) recently convened a Task Force to explore and disseminate advances in epigenetics to better understand their role and intersection with genetics and the neurobiology of epilepsies and their co‐morbidities, and to accelerate translation of these findings into the development of better therapies. Here, we provide a topic primer on epigenetics, explaining the key processes and findings to date in experimental and human epilepsy. We review the growing list of genes with epigenetic functions that have been linked with epilepsy in humans. We consider potential practical applications, including using epigenetic signals as biomarkers for tissue‐ and biofluid‐based diagnostics and the prospects for developing epigenetic‐based treatments for epilepsy. We include a glossary of terms, FAQs and other supports to facilitate a broad understanding of the topic for the non‐expert. Last, we review the limitations, research gaps and the next challenges. In summary, epigenetic processes represent important mechanisms controlling the activity of genes, providing opportunities for insight into disease mechanisms, biomarkers and novel therapies for epilepsy.

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“…Kabuki Syndrome type I (KS, OMIM#147920) is a rare multi-systemic disorder, manifested by craniofacial anomalies including cleft lip/palate and microcephaly, hearing loss, neurodevelopmental defects, epilepsy, skeletal and skin abnormalities, and congenital heart defects (CHD) (1) (2-4) (5-7) (8) (9)(10)(11). While there is variable expressivity of the clinical hallmarks (8,12), CHD is present in ~70% of KS patients, with a unique predilection for left-sided obstructive lesions, including hypoplastic aortic arch, coarctation of the aorta and hypoplastic left heart syndrome (13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Notch signaling rescues cardiovascular development in Kabuki Syndrome

Serrano

Demarest

Tone-Pah-Hote

et al. 2018

Preprint

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Kabuki Syndrome patients have a spectrum of congenital disorders, including congenital heart defects, the primary determinant of mortality. Seventy percent of Kabuki Syndrome patients have mutations in the histone methyl-transferase KMT2D. However, the underlying mechanisms that drive these congenital disorders are unknown. Here, we generated and characterized a zebrafish kmt2d null mutant that recapitulates the cardinal phenotypic features of Kabuki Syndrome, including microcephaly, palate defects, abnormal ear development and cardiac defects. The cardiovascular defects consist of abnormal aortic arches and hypoplastic ventricle, driven by previously unknown aberrant endocardial and endothelial vasculogenesis. We identify a regulatory link between the Notch pathway and Kmt2d during vasculogenesis and show that pharmacological inhibition of Notch signaling rescues the cardiovascular phenotype in zebrafish Kabuki Syndrome. Taken together these findings demonstrate that Kmt2d regulates vasculogenesis, provide evidence for interactions between Kmt2d and Notch signaling in Kabuki Syndrome, and suggest future directions for clinical research.

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Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations

Cited by 20 publications

References 31 publications

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome

Epigenetics explained: a topic “primer” for the epilepsy community by the ILAE Genetics/Epigenetics Task Force

Inhibition of Notch signaling rescues cardiovascular development in Kabuki Syndrome

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