KCNQ2 encephalopathy manifesting with Rett-like features

Mastrangelo, Mario; Manti, Filippo; Giannini, Maria Teresa; Guerrini, Renzo; Leuzzi, Vincenzo

doi:10.1212/nxg.0000000000000510

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…Potassium channel, voltage-gated, kqt-like subfamily, member 2 (KCNQ2) pathogenic variants cause benign neonatal epilepsy and KCNQ2-related encephalopathy. A hyperkinetic MD has been increasingly recognized, but also parkinsonism (bradykinesia, hypomimia and hypoactivity) has been reported [44]. Together with early-onset epilepsy, six patients (three males) also presented with an RTT-like phenotype, featuring regression, abnormal early development, impaired/absent hand use and stereotypies (including hand flapping/washing/mouthing) in half, while the majority are non-ambulant and non-verbal, with profound DD.…”

Section: Kcnq2mentioning

confidence: 99%

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Rett Syndrome Spectrum in Monogenic Developmental-Epileptic Encephalopathies and Epilepsies: A Review

Spagnoli

Fusco

Pisani

2021

Genes

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Introduction: Progress in the clinical application of next-generation-sequencing-based techniques has resulted in a dramatic increase in the recognized genetic heterogeneity of the Rett syndrome spectrum (RSS). Our awareness of the considerable overlap with pediatric-onset epilepsies and epileptic/developmental encephalopathies (EE/DE) genes is also growing, and the presence of variable clinical features inside a general frame of commonalities has drawn renewed attention into deep phenotyping. Methods: We decided to review the medical literature on atypical Rett syndrome and “Rett-like” phenotypes, with special emphasis on described cases with pediatric-onset epilepsies and/or EE-DE, evaluating Neul’s criteria for Rett syndrome and associated movement disorders and notable stereotypies. Results: “Rett-like” features were described in syndromic and non-syndromic monogenic epilepsy- and DE/EE-related genes, in “intellectual disability plus epilepsy”-related genes and in neurodegenerative disorders. Additionally, prominent stereotypies can be observed in monogenic complex neurodevelopmental disorders featuring epilepsy with or without autistic features outside of the RSS. Conclusions: Patients share a complex neurodevelopmental and neurological phenotype (developmental delay, movement disorder) with impaired gait, abnormal tone and hand stereotypies. However, the presence and characteristics of regression and loss of language and functional hand use can differ. Finally, the frequency of additional supportive criteria and their distribution also vary widely.

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Section: Kcnq2mentioning

confidence: 99%

“…The most represented (100%) supportive criteria are abnormal tone; only one patient has more than 5 supportive criteria. Of note, two out of six have abnormal brain MRI, including fronto-insular atrophy [12,42,44,45].…”

Section: Kcnq2mentioning

confidence: 99%

Rett Syndrome Spectrum in Monogenic Developmental-Epileptic Encephalopathies and Epilepsies: A Review

Spagnoli

Fusco

Pisani

2021

Genes

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“…Patient 3 is heterozygous for a de novo substitution mutation (c.977T>G; p. Ile326Arg; CADD PHRED score: 26.2) in the ATP1A2 gene, which is a private mutation. Analysis of patient 4's exome revealed a de novo substitution mutation in the gene KCNQ2 (c.740C>A; p.Ser247Ter; CADD PHRED score: 41), which is associated with early infantile epileptic encephalopathy [30,55]. This variant is predicted to be targeted by nonsense-mediated decay (NMD).…”

Section: Clinical and Molecular Characterization Of Pathogenic Variantsmentioning

confidence: 99%

Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders

Frankel

Podder

Sharifi

et al. 2023

Cells

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Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) cause classical forms of Rett syndrome (RTT) in girls. A subset of patients who are recognized to have an overlapping neurological phenotype with RTT but are lacking a mutation in a gene that causes classical or atypical RTT can be described as having a ‘Rett-syndrome-like phenotype (RTT-L). Here, we report eight patients from our cohort diagnosed as having RTT-L who carry mutations in genes unrelated to RTT. We annotated the list of genes associated with RTT-L from our patient cohort, considered them in the light of peer-reviewed articles on the genetics of RTT-L, and constructed an integrated protein–protein interaction network (PPIN) consisting of 2871 interactions connecting 2192 neighboring proteins among RTT- and RTT-L-associated genes. Functional enrichment analysis of RTT and RTT-L genes identified a number of intuitive biological processes. We also identified transcription factors (TFs) whose binding sites are common across the set of RTT and RTT-L genes and appear as important regulatory motifs for them. Investigation of the most significant over-represented pathway analysis suggests that HDAC1 and CHD4 likely play a central role in the interactome between RTT and RTT-L genes.

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“…In the Clinical/Scientific Note “KCNQ2 encephalopathy manifesting with Rett-like features: A follow-up into adulthood” by Mastrangelo et al, 1 the first sentence of the fifth paragraph should read, “A next-generation sequencing panel that included 140 genes involved in genetic epilepsies revealed the de novo heterozygous KCNQ2 variant c.629 G > C (p.Arg210Pro), which was not present in the Human Gene Mutation Database (portal.biobase-international.com/). ” The authors regret the error.…”

mentioning

confidence: 99%