Pathogenic Role of the X-Linked Cyclin-Dependent Kinase-Like 5 and Aristaless-Related Homeobox Genes in Epileptic Encephalopathy of Unknown Etiology With Onset in the First Year of Life

Abstract Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus. De novo variants in genes that mediate synaptic transmission such as SCN1A and PCDH19 are often associated with Dravet syndrome. Recently, GABAA receptor subunit genes (GABRs) encoding α1 (GABRA1), β3 (GABRB3) and γ2 (GABRG2), but not β2 (GABRB2) or β1 (GABRB1), subunits are frequently associated with Dravet syndrome or Dravet syndrome-like phenotype. We performed next generation sequencing on 870 patients with Dravet syndrome and identified nine variants in three different GABRs. Interestingly, the variants were all in genes encoding the most common GABAA receptor, the α1β2γ2 receptor. Mutations in GABRA1 (c.644T>C, p.L215P; c.640C>T, p.R214C; c.859G>A; V287I; c.641G>A, p.R214H) and GABRG2 (c.269C>G, p.T90R; c.1025C>T, p.P342L) presented as de novo cases, while in GABRB2 two variants were de novo (c.992T>C, p.F331S; c.542A>T, p.Y181F) and one was autosomal dominant and inherited from the maternal side (c.990_992del, p.330_331del). We characterized the effects of these GABR variants on GABAA receptor biogenesis and channel function. We found that defects in receptor gating were the common deficiency of GABRA1 and GABRB2 Dravet syndrome variants, while mainly trafficking defects were found with the GABRG2 (c.269C>G, p.T90R) variant. It seems that variants in α1 and β2 subunits are less tolerated than in γ2 subunits, since variant α1 and β2 subunits express well but were functionally deficient. This suggests that all of these GABR variants are all targeting GABR genes that encode the assembled α1β2γ2 receptor, and regardless of which of the three subunits are mutated, variants in genes coding for α1, β2 and γ2 receptor subunits make them candidate causative genes in the pathogenesis of Dravet syndrome.

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Acute Bronchiolitis: Is There a Role for Lung Ultrasound?

Diagnostics ◽

10.3390/diagnostics9040172 ◽

2019 ◽

Vol 9 (4) ◽

pp. 172 ◽

Cited By ~ 4

Author(s):

Di Mauro ◽

Ammirabile ◽

Quercia ◽

Panza ◽

Capozza ◽

...

Keyword(s):

Clinical Management ◽

Lung Ultrasound ◽

Ultrasound Examination ◽

Diagnostic Algorithm ◽

Current Evidence ◽

Radiographic Examination ◽

First Year ◽

Pubmed Database ◽

First Year Of Life

Introduction: Viral bronchiolitis is a common cause of lower respiratory tract infection in the first year of life, considered a health burden because of its morbidity and costs. Its diagnosis is based on history and physical examination and the role of radiographic examination is limited to atypical cases. Thus far, Lung Ultrasound (LUS) is not considered in the diagnostic algorithm for bronchiolitis. Methods: PubMed database was searched for trials reporting on lung ultrasound examination and involving infants with a diagnosis of bronchiolitis. Results: Eight studies were suitable. Conclusions: This review analyzed the current evidence about the potential usefulness of LUS in the clinical management of bronchiolitis. Literature supports a peculiar role of LUS in the evaluation of the affected children, considering it as a reliable imaging test that could benefit the clinical management of bronchiolitis.

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

Developmental Medicine & Child Neurology ◽

10.1111/j.1469-8749.2010.03889.x ◽

2011 ◽

Vol 53 (4) ◽

pp. 354-360 ◽

Cited By ~ 42

Author(s):

FEDERICO MELANI ◽

DAVIDE MEI ◽

TIZIANA PISANO ◽

SALVATORE SAVASTA ◽

EMILIO FRANZONI ◽

...

Keyword(s):

Epileptic Encephalopathy ◽

First Year ◽

First Year Of Life

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

Developmental Medicine & Child Neurology ◽

10.1111/j.1469-8749.2010.03888.x ◽

2011 ◽

Vol 53 (4) ◽

pp. 296-297

Author(s):

WILLEM F M ARTS

Keyword(s):

Epileptic Encephalopathy ◽

First Year ◽

First Year Of Life

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Water Balance and ‘Salt Wasting' in the First Year of Life: The Role of Aldosterone-Signaling Defects

Hormone Research in Paediatrics ◽

10.1159/000449057 ◽

2016 ◽

Vol 86 (3) ◽

pp. 143-153 ◽

Cited By ~ 12

Author(s):

Carla Bizzarri ◽

Stefania Pedicelli ◽

Marco Cappa ◽

Stefano Cianfarani

Keyword(s):

Water Balance ◽

First Year ◽

Salt Wasting ◽

First Year Of Life

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Molecular diagnosis of epileptic encephalopathy of the first year of life applying a customized gene panel in a group of Argentinean patients

Epilepsy & Behavior ◽

10.1016/j.yebeh.2020.107322 ◽

2020 ◽

Vol 111 ◽

pp. 107322 ◽

Cited By ~ 1

Author(s):

Matias Juanes ◽

Gabriel Veneruzzo ◽

Mariana Loos ◽

Gabriela Reyes ◽

Hilda Veronica Araoz ◽

...

Keyword(s):

Molecular Diagnosis ◽

Epileptic Encephalopathy ◽

Gene Panel ◽

First Year ◽

First Year Of Life

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No perceptual reorganization for Limburgian tones? A cross-linguistic investigation with 6- to 12-month-old infants

Journal of Child Language ◽

10.1017/s0305000917000228 ◽

2017 ◽

Vol 45 (2) ◽

pp. 290-318 ◽

Cited By ~ 5

Author(s):

STEFANIE RAMACHERS ◽

SUSANNE BROUWER ◽

PAULA FIKKERT

Keyword(s):

Language Acquisition ◽

First Year ◽

Lexical Tone ◽

Linguistic Experience ◽

Tone Languages ◽

First Year Of Life ◽

Visual Habituation ◽

Degree Of Similarity

AbstractDespite the fact that many of the world's languages use lexical tone, the majority of language acquisition studies has focused on non-tone languages. Research on tone languages has typically investigated well-known tone languages such as Mandarin and Cantonese Chinese. The current study looked at a Limburgian dialect of Dutch that uses lexical pitch differences, albeit in a rather restricted way. Using a visual habituation paradigm, 6- to 12-month-old Limburgian and Dutch infants were tested for their ability to discriminate Limburgian tones. The results showed that both Limburgian and Dutch infants discriminate the Limburgian tones throughout their first year of life. The role of linguistic experience, acoustic salience, and the degree of similarity to the native prosodic system are discussed.

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Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report

Frontiers in Neurology ◽

10.3389/fneur.2021.704747 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gianluca Piccolo ◽

Giuseppe d'Annunzio ◽

Elisabetta Amadori ◽

Antonella Riva ◽

Paola Borgia ◽

...

Keyword(s):

Genetic Basis ◽

First Year ◽

Arthrogryposis Multiplex Congenita ◽

Neurodevelopmental Delay ◽

Pathogenic Variants ◽

Phenotypic Spectrum ◽

Distal Muscle ◽

Neurodevelopmental Impairment ◽

First Year Of Life

Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2, encoding a C4H2 type zinc-finger nuclear factor abundantly expressed in the developing human brain. The main clinical features described in WWS families carrying ZC4H2 pathogenic variants encompass having a short stature, microcephaly, birth respiratory distress, arthrogryposis, hypotonia, distal muscle weakness, and broad neurodevelopmental delay. We hereby report a Sicilian family with a boy clinically diagnosed with WWS and genetically investigated with exome sequencing (ES), leading to the identification of a c.593G>A (p. R198Q) hemizygous pathogenic variant in the ZC4H2 gene. During the first year of life, the onset of central hypoadrenalism led to recurrent hypoglycemic events, which likely contributed to seizure susceptibility. Also, muscle biopsy studies confirmed a pathology of the muscle tissue and revealed peculiar abnormalities of the neuromuscular junction. In conclusion, we expand the phenotypic spectrum of the WWS-related neurodevelopmental disorders and discuss the role of ZC4H2 in the context of the potential neuroendocrinological and neuromuscular features associated with this condition.

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XPC and POLH/XPV Genes Mutated in a Genetic Cluster of Xeroderma Pigmentosum Patients in Northeast Brazil

Frontiers in Genetics ◽

10.3389/fgene.2021.784963 ◽

2022 ◽

Vol 12 ◽

Author(s):

Ligia Pereira Castro ◽

Danilo Batista-Vieira ◽

Tiago Antonio de Souza ◽

Ana Rafaela de Souza Timoteo ◽

Jessica Dayanna Landivar Coutinho ◽

...

Keyword(s):

Xeroderma Pigmentosum ◽

High Throughput Sequencing ◽

First Year ◽

Genetic Condition ◽

Genetic Cluster ◽

High Incidence ◽

Comoro Island ◽

First Year Of Life ◽

Defective Dna Repair

Xeroderma pigmentosum (XP) is a rare genetic condition in which exposure to sunlight leads to a high tumor incidence due to defective DNA repair machinery. Herein, we investigated seven patients clinically diagnosed with XP living in a small city, Montanhas (Rio Grande do Norte), in the Northeast region of Brazil. We performed high-throughput sequencing and, surprisingly, identified two different mutated genes. Six patients carry a novel homozygote mutation in the POLH/XPV gene, c.672_673insT (p.Leu225Serfs*33), while one patient carries a homozygote mutation in the XPC gene, c.2251-1G>C. This latter mutation was previously described in Southeastern Africa (Comoro Island and Mozambique), Pakistan, and in a high incidence in Brazil. The XP-C patient had the first symptoms before the first year of life with aggressive ophthalmologic tumor progression and a melanoma onset at 7 years of age. The XP-V patients presented a milder phenotype with later onset of the disorder (mean age of 16 years old), and one of the six XP-V patients developed melanoma at 72 years. The photoprotection is minimal among them, mainly for the XP-V patients. The differences in the disease severity between XP-C (more aggressive) and XP-V (milder) patients are obvious and point to the major role of photoprotection in the XPs. We estimate that the incidence of XP patients at Montanhas can be higher, but with no diagnosis, due to poor health assistance. Patients still suffer from the stigmatization of the condition, impairing diagnosis, education for sun protection, and medical care.

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Things that can be changed in early intervention in childhood

Medicinski pregled ◽

10.2298/mpns1508267g ◽

2015 ◽

Vol 68 (7-8) ◽

pp. 267-272 ◽

Cited By ~ 2

Author(s):

Spela Golubovic ◽

Jasminka Markovic ◽

Lidija Perovic

Keyword(s):

Early Intervention ◽

First Year ◽

Early Age ◽

Special Educator ◽

Professional Help ◽

Early Intervention Services ◽

Rehabilitation Professionals ◽

Novi Sad ◽

First Year Of Life

Introduction. Early intervention implies a model of support focused on a child, family and a broader community from early childhood. The aim of this study was to analyze the elements of the successful early intervention in childhood, as well as to assess the role of a special educator and rehabilitator and level of their involvement in implementing the program on the territory of Novi Sad. Material and Methods. The study sample included 100 parents of children with disabilities (aged 3-7), who completed the questionnaire designed for the purposes of this research, based on a similar questionnaire design. Results. Speech delay is one of the most common reasons (over 50%) why parents seek professional help. By the end of the first year of life of their child, 43% of parents responded that they had noticed the first problems, that is, a problem was identified in 25% of children of this age group, and the same number was included in the treatment. About 55% of children were involved in organized treatment from 3 years of age onwards. Special educators and rehabilitators are usually involved in treatment when the team consists of three or more professionals. Conclusions. It is necessary to improve early intervention services, to educate staff, and provide conditions which would make it possible to overcome the existing disadvantages in treating children from an early age. In addition, the involvement of special education and rehabilitation professionals in treatment teams since children?s early age is vital.

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