Prevalence of neuropsychiatric symptoms associated with malformations of cortical development

Ho, Cyrus S.H.; Dubeau, François; Séguin, René; Ducharme, Simon

doi:10.1016/j.yebeh.2019.01.011

Cited by 13 publications

(8 citation statements)

References 29 publications

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“…We in fact identified a high rate of neuropsychiatric features in our cohort, including aggressive behavior, psychosis, ADHD/Attention deficiency and ASD. The remarkable association of cortical anomalies with neuropsychiatric features is in line with current literature revealing that psychiatric symptoms may occur in up to a third of cases with MCD, including pachygyria [ 16 , 17 ]. Notably, aggressive behavior has also been described in several subjects with biallelic CRADD variants [ 18 ].…”

Section: Discussionsupporting

confidence: 85%

Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features

et al. 2021

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The PIDDosome is a multiprotein complex, composed by the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 that induces apoptosis in response to DNA damage. In the recent years, biallelic pathogenic variants in CRADD have been associated with a neurodevelopmental disorder (MRT34; MIM 614499) characterized by pachygyria with a predominant anterior gradient, megalencephaly, epilepsy and intellectual disability. More recently, biallelic pathogenic variants in PIDD1 have been described in a few families with apparently nonsydnromic intellectual disability. Here, we aim to delineate the genetic and radio-clinical features of PIDD1-related disorder. Exome sequencing was carried out in six consanguineous families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals as well as reviewing all the data from previously reported cases. We identified five distinct novel homozygous variants (c.2584C>T p.(Arg862Trp), c.1340G>A p.(Trp447*), c.2116_2120del p.(Val706Hisfs*30), c.1564_1565delCA p.(Gln522fs*44), and c.1804_1805del p.(Gly602fs*26) in eleven subjects displaying intellectual disability, behaviorial and psychiatric features, and a typical anterior-predominant pachygyria, remarkably resembling the CRADD-related neuroimaging pattern. In summary, we outline the phenotypic and molecular spectrum of PIDD1 biallelic variants supporting the evidence that the PIDD1/CRADD/caspase-2 signaling is crucial for normal gyration of the developing human neocortex as well as cognition and behavior.

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Section: Discussionsupporting

confidence: 85%

Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features

et al. 2021

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“…The adult HD brain also shows various developmental malformations, including periventricular nodular heterotopia (PNH) (most frequent) and immature neuronal populations. PNH is characterized by altered neural migration and is usually associated with drug-resistant epilepsy and various psychiatric disorders ( Fry et al, 2013 ; Jamuar et al, 2014 ; Alcantara et al, 2017 ; Ho et al, 2019 ). Interestingly, PNH can be experimentally reproduced following in utero injection of a genotoxin such as MAM or carmustine ( Moroni et al, 2013 ; Luhmann, 2016 ) suggesting that early-life exposure to environmental genotoxins may be able to trigger similar molecular and neurodevelopmental changes.…”

Section: Genomic Instability and Cycad Toxinsmentioning

confidence: 99%

Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease

Kisby

Spencer

2021

Front. Neurosci.

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Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC) is a disappearing prototypical neurodegenerative disorder (tau-dominated polyproteinopathy) linked with prior exposure to phytogenotoxins in cycad seed used for medicine and/or food. The principal cycad genotoxin, methylazoxymethanol (MAM), forms reactive carbon-centered ions that alkylate nucleic acids in fetal rodent brain and, depending on the timing of systemic administration, induces persistent developmental abnormalities of the cortex, hippocampus, cerebellum, and retina. Whereas administration of MAM prenatally or postnatally can produce animal models of epilepsy, schizophrenia or ataxia, administration to adult animals produces little effect on brain structure or function. The neurotoxic effects of MAM administered to rats during cortical brain development (specifically, gestation day 17) are used to model the histological, neurophysiological and behavioral deficits of human schizophrenia, a condition that may precede or follow clinical onset of motor neuron disease in subjects with sporadic ALS and ALS/PDC. While studies of migrants to and from communities impacted by ALS/PDC indicate the degenerative brain disorder may be acquired in juvenile and adult life, a proportion of indigenous cases shows neurodevelopmental aberrations in the cerebellum and retina consistent with MAM exposure in utero. MAM induces specific patterns of DNA damage and repair that associate with increased tau expression in primary rat neuronal cultures and with brain transcriptional changes that parallel those associated with human ALS and Alzheimer’s disease. We examine MAM in relation to neurodevelopment, epigenetic modification, DNA damage/replicative stress, genomic instability, somatic mutation, cell-cycle reentry and cellular senescence. Since the majority of neurodegenerative disease lacks a solely inherited genetic basis, research is needed to explore the hypothesis that early-life exposure to genotoxic agents may trigger or promote molecular events that culminate in neurodegeneration.

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“…psichikos sutrikimo atvejų. Tyrimas parodė, kad šiuo atveju psichikos sutrikimai nekoreliuoja su pagrindiniais smegenų žievės struktūros pakitimais [20]. Išvados 1.…”

Section: Diskusijaunclassified

Smegenų Žievės Struktūros Pakitimų Įtaka Psichikos Sveikatai

Jaras¹

2021

Health Sciences

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Straipsnyje aprašomas 23 metų pacientės klinikinis atvejis, prasidėjęs bloga nuotaika, nerimo simptomatika, padidėjusiu jautrumu, verksmingumu, sutrikusiu nakties miegu ir po subjektyviai reikšmingos stresogeninės situacijos pasireiškęs staigia psichozine simptomatika. Pacientė jauno amžiaus ir staiga sutrikusi psichikos sveikata buvo indikacija ieškoti galimos organinės patologijos. Gydymo eigoje atlikus detalų ištyrimą ir įvertinus galvos smegenų MRT vaizdus, nustatytas įgimtas galvos smegenų Silvijaus vagos išplitimas, galvos smegenų mikrogirija ir pachigirija. Tyrimo tikslas – pristatyti galimus psichikos būklės pasikeitimus ir simptomus, esant įgimtiems galvos smegenų struktūros pakitimams.

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Prevalence of neuropsychiatric symptoms associated with malformations of cortical development

Cited by 13 publications

References 29 publications

Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features

Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features

Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease

Smegenų Žievės Struktūros Pakitimų Įtaka Psichikos Sveikatai

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