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1.
Am J Med Genet A ; 194(2): 211-217, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37795572

RESUMO

Tatton-Brown-Rahman syndrome (TBRS) or DNMT3A-overgrowth syndrome is characterized by overgrowth and intellectual disability associated with minor dysmorphic features, obesity, and behavioral problems. It is caused by variants of the DNMT3A gene. We report four patients with this syndrome due to de novo DNMT3A pathogenic variants, contributing to a deeper understanding of the genetic basis and pathophysiology of this autosomal dominant syndrome. Clinical and magnetic resonance imaging assessments were also performed. All patients showed corpus callosum anomalies, small posterior fossa, and a deep left Sylvian fissure; as well as asymmetry of the uncinate and arcuate fascicles and marked increased cortical thickness. These results suggest that structural neuroimaging anomalies have been previously overlooked, where corpus callosum and brain tract alterations might be unrecognized neuroimaging traits of TBRS syndrome caused by DNMT3A variants.


Assuntos
Anormalidades Múltiplas , Deficiência Intelectual , Anormalidades Musculoesqueléticas , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/genética , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Anormalidades Múltiplas/genética , Anormalidades Musculoesqueléticas/complicações , Síndrome , Neuroimagem
2.
Memory ; : 1-20, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588660

RESUMO

Electrophysiological and behavioural correlates of true and false memories were examined in the Deese/Roediger-McDermont (DRM) paradigm. A mass univariate approach for analysing event-related potentials (ERP) in the temporal domain was used to examine the electrophysiological effects associated with this paradigm precisely (point-by-point) and without bias (data-driven). Behaviourally, true and false recognition did not differ, and the predicted DRM effect was observed, as false recognition of critical lures (i.e., new words semantically related to studied words) was higher than false alarms of new (unrelated) words. Neurally, an expected old/new effect was observed during the time-range of the late positive component (LPC) over left centro-parietal scalp electrodes. Furthermore, true recognition also evoked larger LPC amplitudes than false recognition over both left centro-parietal and fronto-central scalp electrodes. However, we did not observe LPC-related differences between critical lures and new words, nor between correct rejections of critical lures and new words. In contrast, correct rejections of critical lures were accompanied by higher activation of a sustained positive slow wave (SPSW) in right fronto-central electrodes beyond 1200 ms. This result reveals a key role of post-retrieval processes in recognition. Results are discussed in light of theoretical approaches to false memory in the DRM paradigm.

3.
Dev Sci ; 25(5): e13210, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34873804

RESUMO

Although progress has been made in elucidating the behavioral and neural development of global stopping across the lifespan, little is known about the development of selective stopping. This more complex form of inhibitory control is required in real-world situations where ongoing responses must be inhibited to certain stimuli but not others, and can be assessed in laboratory settings using a stimulus selective stopping task. Here we used this task to investigate the qualitative and quantitative developmental changes in selective stopping in a large-scale cross-sectional study with three different age groups (children, preadolescents, and young adults). We found that the ability to stop a response selectively to some stimuli (i.e., use a selective strategy) rather than non-selectively to all presented stimuli (i.e., use a global, non-selective strategy) is fully mature by early preadolescence, and remains stable afterwards at least until young adulthood. By contrast, the efficiency or speed of stopping (indexed by a shorter stop-signal reaction time or SSRT) continues to mature throughout adolescence until young adulthood, both for global and selective implementations of stopping. We also provide some preliminary findings regarding which other task variables beyond the strategy and SSRT predicted age group status. Premature responding (an index of "waiting impulsivity") and post-ignore slowing (an index of cognitive control) were among the most relevant predictors in discriminating between developmental age groups. Although present results need to be confirmed and extended in longitudinal studies, they provide new insights into the development of a relevant form of inhibitory control.


Assuntos
Comportamento Impulsivo , Inibição Psicológica , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Tempo de Reação/fisiologia , Adulto Jovem
4.
Neurocase ; 28(1): 11-18, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35253627

RESUMO

. COL18A1 gene mutations have been associated with Knobloch syndrome, which is characterized by ocular and brain abnormalities. Here we report a 4.5 years-old male child with autism and two novel COL18A1 mutations (NM_030582.4: c.1883_1891dup and c.1787C>T). Hypermetropic astigmatism, but not brain migration disorders, was observed. However, an asymmetric pattern of cerebellar perfusion and a smaller arcuate fascicle were found.  Low levels of collagen XVIII were also observed in the patient´s serum. Thus, biallelic loss-of-function mutations in COL18A1 may be a new cause of autism  without the brain malformations typically reported in patients with Knobloch syndrome.


Assuntos
Colágeno Tipo XVIII , Endostatinas , Cerebelo , Pré-Escolar , Colágeno Tipo XVIII/genética , Encefalocele , Endostatinas/genética , Humanos , Masculino , Mutação , Neuroimagem , Degeneração Retiniana , Descolamento Retiniano/congênito
5.
Medicina (B Aires) ; 79(Suppl 1): 57-61, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30776281

RESUMO

Attention deficit / hyperactivity disorder (ADHD) is one of the most prevalent disorders in the child-youth population, with a known impact on learning and school performance. Lack of attention, associated executive dysfunction and comorbid problems -particularly those related to learning and anxiety-, strongly determine this conceptual domain. Affected youths have more problems for taking notes, completion of homework, school programming and less motivation to study. Despite greater dedication to homework and greater use of support resources, school failure and nonachievement of curricular objectives are more frequent in these patients. The early diagnosis of ADHD and its comorbidities, the adequate and individualized psychoeducational and pharmacological intervention, have been shown to improve academic prognosis in the short and long term. For this purpose, the active participation of health and education professionals is essential.


El trastorno por déficit de atención/hiperactividad (TDAH) es uno de los trastornos más prevalentes en la población infanto-juvenil, con un impacto ya conocido sobre el aprendizaje y rendimiento escolar. La falta de atención, la disfunción ejecutiva asociada y los problemas comórbidos ­particularmente los relacionados con el aprendizaje y la ansiedad­, condicionan marcadamente este dominio conceptual. Los jóvenes afectos, tienen más problemas para la toma de apuntes, finalización de trabajos, programación escolar y menor motivación al estudio. A pesar de una mayor dedicación al estudio y mayor uso de recursos de apoyo, el fracaso escolar y la no consecución de objetivos curriculares son más frecuentes en estos pacientes. El diagnóstico temprano del TDAH y sus comorbilidades, la intervención psicoeducativa y farmacológica adecuada e individualizada, han demostrado mejorar el pronóstico académico a corto y largo plazo. Para este propósito, es imprescindible la participación activa de profesionales de la salud y la educación.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Hábitos , Desempenho Acadêmico/psicologia , Adolescente , Ansiedade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Criança , Pré-Escolar , Comorbidade , Humanos , Aprendizagem , Deficiências da Aprendizagem/complicações , Deficiências da Aprendizagem/psicologia , Deficiências da Aprendizagem/terapia
6.
Actas Esp Psiquiatr ; 47(4): 158-64, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31461155

RESUMO

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent disorders in the child and adolescent population, with a known impact on learning, social relations and quality of life. However, the lifestyle habits of patients with this disorder have been poorly studied. MATERIAL AND METHODS: A total of 160 children and adolescents, aged between 6 and 16 years, participated in the study. Half of them were treatment-naïve patients with a clinical diagnosis of ADHD according to DSM-IV-TR criteria, and without comorbidities. The remaining 80 participants were typically developing (TD) controls without known neurodevelopmental or psychiatric disorders. Parents of all participants completed a questionnaire about their children´s lifestyle habits (e.g, daily hours of sleep, media use and study). RESULTS: The groups had a similar socioeconomic background and did not differ with respect to age and sex distribution. However, patients with ADHD spent more time than TD children studying, and less time watching TV, playing video games, using computers and playing with other people. They also slept fewer hours per night than children and adolescents with TD. ADHD and TD groups spent similar time reading, listening to music and playing sports. CONCLUSIONS: The results of this study suggest that children and adolescents with ADHD have different lifestyle habits compared to age- and sex-matched controls. These findings are not explained by comorbid disorders or medication/ psychological treatment.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Hábitos , Estilo de Vida , Adolescente , Criança , Comportamento Infantil , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pais , Inquéritos e Questionários , Jogos de Vídeo
7.
Am J Med Genet A ; 164A(8): 2074-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24782348

RESUMO

LBX1 plays a cardinal role in neuronal and muscular development in animal models. Its function in humans is unknown; it has been reported as a candidate gene for idiopathic scoliosis. Our goal is to document the first clinical case of a microduplication at 10q24.31 (chr10:102927883-103053612, hg19), affecting exclusively LBX1. The patient, a 12-year-old girl, showed attention problems, dyspraxia, idiopathic congenital scoliosis, and marked hypotrophy of paravertebral muscles. Her paternal aunt had a severe and progressive myopathy with a genetic study that revealed the same duplication. We propose to consider genetic studies, particularly of LBX1, in patients with scoliosis and/or hypotrophy-hypoplasia of paravertebral muscles of unknown etiology.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 10 , Doenças Musculares/genética , Escoliose/genética , Criança , Hibridização Genômica Comparativa , Feminino , Estudos de Associação Genética , Proteínas de Homeodomínio/genética , Humanos , Imageamento por Ressonância Magnética , Doenças Musculares/diagnóstico , Fenótipo , Radiografia , Escoliose/diagnóstico , Espanha , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Fatores de Transcrição/genética
8.
Childs Nerv Syst ; 30(12): 2157-61, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24980605

RESUMO

CASE REPORT: We describe an unusual clinical case with an 11-Mb deletion at 4q27 (chr4: 123094652-134164491), craniosynostosis (CS), mild psychomotor retardation, and facial dysmorphic features. This deletion involves 18 genes; FGF2, NUDT6, and SPRY1 are primarily or secondarily implicated in human cranial bone and sagittal suture development and could play an important role in CS. CONCLUSIONS: Clinicians should always contemplate genetic studies in patients with syndromic CS. Mutational targeted genetic testing is appropriate for patients with classical or specific CS syndrome. Nevertheless, array comparative genomic hybridization (array CGH) should be considered as a first-line test in nontypical syndromic CS phenotype. Cytogenetic studies are decisive for genetic counseling indeed.


Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 4/genética , Craniossinostoses/genética , Deficiência Intelectual/genética , Atrofia Muscular/genética , Transtornos Psicomotores/genética , Criança , Anormalidades Craniofaciais , Fácies , Retardo do Crescimento Fetal/genética , Fator 2 de Crescimento de Fibroblastos/genética , Estudos de Associação Genética , Aconselhamento Genético , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Proteínas de Membrana/genética , Fosfoproteínas/genética , Proteínas/genética
9.
Medicina (B Aires) ; 84 Suppl 1: 26-30, 2024 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-38350621

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a complex and heterogeneous neurodevelopmental disorder from a causal, clinical and prognostic perspective. Research reflects its multifactorial nature with a prominent role of genetic factors. Population studies have historically pointed to the involvement of numerous genetic variants of small effect size, which hardly by themselves increase the risk of presenting the disorder and hardly justify its high heritability. Many of them are present in more than 60% of the general population, suggesting their modulatory rather than causal role. However, after the irruption of new genetic techniques in the last 15 years, a greater number of cases are being identified with genetic disorders (many of them monogenic), whose genetic variants alone explain the presence of ADHD. A detailed study of the personal and family history, as well as a complete physical examination, can help to identify some of them. The identification of the cause in this group of cases has a crucial value in clinical counseling, genetic-familial counseling and prognostic anticipation, as well as in the performance or avoidance of complementary studies and in the design of the intervention plan.


El trastorno por déficit de atención/hiperactividad (TDAH) es un trastorno del neurodesarrollo complejo y heterogéneo desde una perspectiva causal, clínica y pronóstica. La investigación refleja su carácter multifactorial con un papel destacado de los factores genéticos. Los estudios poblacionales han señalado históricamente la implicación de numerosas variantes genéticas de escaso tamaño de efecto, las cuales por sí mismas apenas incrementan el riesgo de TDAH y difícilmente justifican su elevada heredabilidad. Muchas de ellas están presentes en más del 60% de la población general, lo que sugiere su papel modulador más que causal. No obstante, gracias a la irrupción de nuevas técnicas genéticas en los últimos 15 años, se están identificando un mayor número de casos con trastornos genéticos (muchos de ellos monogénicos), cuyas variantes genéticas explican por sí mismas la presencia del TDAH. El estudio detallado de los antecedentes personales y familiares, así como una exploración física completa, puede ayudar a identificar algunos de ellos. La identificación de la causa en este conjunto de casos tiene un valor crucial en el asesoramiento clínico, el consejo genético-familiar y la anticipación pronóstica, así como en la realización o evitación de estudios complementarios y en el diseño del plan terapéutico.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtornos do Neurodesenvolvimento , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Projetos de Pesquisa , Predisposição Genética para Doença
10.
Neuroimage ; 76: 272-81, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23523776

RESUMO

Despite an extensive literature on the neural substrates of response inhibition, when and where this process occurs in the brain remain unclear. The present study aimed to shed light on this issue by exploiting the high temporal resolution of the event-related potentials (ERPs) and recent advances in source localization. Temporo-spatial principal component analysis was employed to define more precisely the two ERP components most often associated with response inhibition (i.e., frontocentral N2 and frontocentral P3), as well as to improve the accuracy of source localization. In addition, participants (N=40) performed a modified Go/Nogo task composed of three types of stimuli (frequent-Go, infrequent-Go, and infrequent-Nogo), which allowed us to dissociate neural activity associated with response inhibition from that related to novelty processing by directly contrasting nogo and go trials matched with respect to frequency of occurrence. Scalp ERP data indicated that the frontocentral P3, but not the frontocentral N2, showed larger amplitudes for infrequent-Nogo than for infrequent-Go trials. Source localization data parallel the results obtained at the scalp level: only P3-related activity showed differences between infrequent-Nogo and infrequent-Go trials. This increased activation was observed predominantly in the presupplementary motor area (preSMA). Present results suggest that the frontocentral P3 and the preSMA play a core role in response inhibition. The findings of this study substantiate and complement previous results obtained by hemodynamic procedures.


Assuntos
Encéfalo/fisiologia , Potenciais Evocados P300/fisiologia , Inibição Psicológica , Adulto , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Estimulação Luminosa , Análise de Componente Principal , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Adulto Jovem
11.
Brain Cogn ; 83(1): 10-20, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23867737

RESUMO

Although, in everyday life, patients with attention deficit hyperactivity disorder (ADHD) are frequently distracted by goal-irrelevant affective stimuli, little is known about the neural and behavioral substrates underlying this emotional distractibility. Because some of the most important brain responses associated with the sudden onset of an emotional distracter are characterized by their early latency onset and short duration, we addressed this issue by using a temporally agile neural signal capable of detecting and distinguishing them. Specifically, scalp event-related potentials (ERPs) were recorded while 20 boys with ADHD combined type and 20 healthy comparison subjects performed a digit categorization task during the presentation of three types of irrelevant, distracting stimuli: arousing negative (A-), neutral (N) and arousing positive (A+). Behavioral data showed that emotional distracters (both A- and A+) were associated with longer reaction times than neutral ones in the ADHD group, whereas no differences were found in the control group. ERP data revealed that, compared with control subjects, boys with ADHD showed larger anterior N2 amplitudes for emotional than for neutral distracters. Furthermore, regression analyses between ERP data and subjects' emotional ratings of distracting stimuli showed that only in the ADHD group, emotional arousal (ranging from calming to arousing) was associated with anterior N2: its amplitude increased as the arousal content of the visual distracter increased. These results suggest that boys with ADHD are more vulnerable to the distracting effects of irrelevant emotional stimuli than control subjects. The present study provides first data on the neural substrates underlying emotional distractibility in ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Comportamento/fisiologia , Encéfalo/fisiopatologia , Emoções/fisiologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Potenciais Evocados/fisiologia , Humanos , Masculino , Tempo de Reação , Percepção Visual/fisiologia
12.
Medicina (B Aires) ; 83 Suppl 2: 22-26, 2023 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-36820478

RESUMO

Beyond the frequent coexistence of attention deficit hyperactivity disorder (ADHD) and reading disorder (dyslexia), the present review aims to examine the available empirical evidence on how ADHD negatively impacts on learning to read. Existing data suggest that the presence of the disorder (especially inattention symptoms), may affect i) the correct acquisition of reading, either directly or through its influence on the precursors to reading; ii) decoding skills themselves (reading accuracy and fluency), both directly and indirectly through its influence on cognitive processes such as distractibility or executive functions; and iii) reading comprehension, probably indirectly through the executive and verbal memory difficulties characteristic of ADHD. These findings have important implications for better characterizing and intervening on reading difficulties in ADHD, whether clinical or subclinical.


Más allá de la frecuente coexistencia del trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno específico del aprendizaje de la lectura, la presente revisión pretende examinar la evidencia empírica disponible sobre cómo el TDAH impacta negativamente sobre el aprendizaje de la lectura. Los datos existentes apuntan a que la presencia del trastorno (especialmente los síntomas de falta de atención), puede afectar a i) la correcta adquisición de lectura, ya sea de manera directa o a través de su influencia sobre los precursores de la lectura; ii) las propias habilidades de decodificación (precisión y fluidez lectora), tanto de manera directa como indirecta a través de su influencia sobre procesos cognitivos como la distracción o las funciones ejecutivas; y ii) la comprensión lectora, probablemente de manera indirecta por las dificultades ejecutivas y en la memoria de trabajo verbal características del TDAH. Estas conclusiones presentan importantes implicaciones para caracterizar e intervenir mejor sobre las dificultades lectoras en el TDAH, ya sean clínicas o subclínicas.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Dislexia , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Compreensão , Aprendizagem , Cognição , Função Executiva , Dislexia/complicações , Dislexia/psicologia
13.
Hum Brain Mapp ; 33(9): 2147-60, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21901794

RESUMO

Although the involvement of the anterior cingulate cortex (ACC) in emotional response inhibition is well established, there are several outstanding issues about the nature of this involvement that are not well understood. The present study aimed to examine the precise contribution of the ACC to emotion-modulated response inhibition by capitalizing on fine temporal resolution of the event-related potentials (ERPs) and the recent advances in source localization. To this end, participants (N = 30) performed an indirect affective Go/Nogo task (i.e., unrelated to the emotional content of stimulation) that required the inhibition of a motor response to three types of visual stimuli: arousing negative (A-), neutral (N), and arousing positive (A+). Behavioral data revealed that participants made more commission errors to A+ than to N and A-. Electrophysiological data showed that a specific region of the ACC at the intersection of its dorsal and rostral subdivisions was significantly involved in the interaction between emotional processing and motor inhibition. Specifically, activity reflecting this interaction was observed in the P3 (but not in the N2) time range, and was greater during the inhibition of responses to A+ than to N and A-. Additionally, regression analyses showed that inhibition-related activity within this ACC region was associated with the emotional content of the stimuli (its activity increased as stimulus valence was more positive), and also with behavioral performance (both with reaction times and commission errors). The present results provide additional data for understanding how, when, and where emotion interacts with response inhibition within the ACC.


Assuntos
Emoções/fisiologia , Giro do Cíngulo/fisiologia , Inibição Psicológica , Adulto , Cor , Sinais (Psicologia) , Interpretação Estatística de Dados , Eletroencefalografia , Feminino , Giro do Cíngulo/anatomia & histologia , Humanos , Masculino , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Análise de Regressão , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-36011868

RESUMO

BACKGROUND: European countries apply a policy of deterrence of migrants in territorial and extraterritorial border areas. The authors apply the model of torturing environments, which has been already applied to other contexts where persons are deprived of liberty, to the situation of the reception center of Moria, on the island of Lesvos (Greece). METHODS: A cross-sectional study was conducted in the months of April and June of 2020. Personal interviews were conducted with 160 people (80 men, 80 women) from Afghan, Syrian, Somalian, and Congo backgrounds. The authors applied the Torturing Environmental Scale, which measures interpersonal violence, emotional distress, and legal safeguards. RESULTS: The findings confirm the inhumane living conditions for the people sheltered in Moria, documenting the severe suffering of the population due to elements linked to basic human functions (hunger, thirst, hygiene, overcrowding, temperature, etc.), actions that produce fear and distress, actions that produce helplessness and hopelessness, actions that cause physical pain, attacks on sexual integrity, and attacks on identity and the need to belong. Some of the data suggest that the purposive and intentionality elements of the definition of cruel, inhuman, or degrading treatment were also met. CONCLUSIONS: According to the conceptual model of torturing environments, the Moria reception camp constitutes a space of systematic ill treatment that vulnerated the European legal standards related to torture (Article 3 of the Human Rights Convention). The idea of torturing environments provides a valuable avenue to assess human rights violations in collective spaces and could constitute a useful tool in forensic and litigation processes.


Assuntos
Refugiados , Tortura , Estudos Transversais , Feminino , Grécia , Direitos Humanos , Humanos , Masculino , Campos de Refugiados
15.
Mol Syndromol ; 13(2): 165-170, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35418825

RESUMO

Bi-allelic mutations in the TUBGCP4 gene have been recently associated with autosomal recessive microcephaly with chorioretinopathy. However, little is known about the genotype-phenotype characteristics of this disorder. Here, we describe a 5-year-old male patient with autism and a normal occipitofrontal circumference. No retinal abnormalities were observed. Brain MRI revealed the presence of enlarged sheaths of both tortuous optic nerves; both eyes had shorter axial lengths. Whole-exome sequencing in trio revealed synonymous TUBGCP4 variants in homozygous state: c.1746G>T; p.Leu582=. This synonymous variant has been previously described and probably leads to skipping of exon 16 of TUBGCP4. These results broaden the clinical spectrum of this new syndrome and suggest that TUBGCP4 bi-allelic mutations may underlie complex neurodevelopmental disorders.

16.
Medicina (B Aires) ; 82 Suppl 1: 23-27, 2022 Feb 02.
Artigo em Espanhol | MEDLINE | ID: mdl-35171803

RESUMO

This study aims to contribute to a better understanding of attention deficit hyperactivity disorder (ADHD) by comprehensively examining the relationship between two of the main cognitive deficits of the disorder (attention and inhibitory control), symptomatology (inattention and hyperactivity/impulsivity) and functional impairment in 85 children and adolescents with ADHD without other comorbid disorders. We found, independent of general intellectual functioning and age, that i) greater attentional and inhibitory deficits predicted greater severity of ADHD symptoms, ii) greater attentional and inhibitory deficits predicted greater functional impairment, but not in a direct way but through symptoms, and iii) greater symptomatic severity predicted greater functional impairment. Beginning to explore and understand the complexity of ADHD is key to advance our knowledge of the disorder and for correct clinical decision making.


Este estudio pretende contribuir a una mejor comprensión del trastorno por déficit de atención con hiperactividad (TDAH) examinado de manera exhaustiva la relación entre dos de los principales déficits cognitivos del trastorno (la atención y el control inhibitorio), la sintomatología (falta de atención e hiperactividad / impulsividad) y la repercusión funcional en 85 niños/as y adolescentes con TDAH sin otros trastornos comórbidos. Encontramos, con independencia del funcionamiento intelectual general y de la edad, que i) un mayor déficit atencional e inhibitorio, predijo una mayor gravedad de los síntomas del TDAH, ii) un mayor déficit atencional e inhibitorio predijo un mayor deterioro funcional, pero no de una manera directa sino a través de los síntomas, y iii) una mayor severidad sintomática predijo una mayor repercusión funcional. Comenzar a explorar y comprender la complejidad del TDAH es clave para avanzar en nuestro conocimiento del trastorno y para la correcta toma de decisiones clínicas.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtornos Cognitivos , Disfunção Cognitiva , Adolescente , Criança , Cognição , Disfunção Cognitiva/diagnóstico , Humanos
17.
Appl Neuropsychol Child ; 11(4): 921-927, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34470565

RESUMO

Mutations in the PQBP1 gene are associated with Renpenning syndrome (RENS1, MIM# 309500). Most cases are characterized by intellectual disability, but a detailed neuropsychological profile has not yet been established. The present case study of a 8.5 years-old male child with a missense novel mutation in the PQBP1 gene expands existing understanding of this syndrome by presenting a milder clinical and neuropsychological phenotype. Whole exome trio analysis sequencing revealed a maternally inherited PQBP1 missense mutation in chromosome X [NM_001032383.1, c.727C > T (p.Arg243Trp)]. Variant functional studies demonstrated a significant reduction in the interaction between PQBP1 and the component of the nuclear pre-mRNA splicing machinery, U5-15KD. A comprehensive neuropsychological assessment revealed marked deficits in processing speed, attention and executive functioning (including planning, inhibitory control and working memory) without intellectual disability. Several components of language processing were also impaired. These results support that this mutation partially disrupts the function of this gene, which is known to play critical roles in embryonic and neural development. As most of the genomic PQBP1 abnormalities associated with intellectual disability have been found to be loss-of-function mutations, we hypothesize that a partial loss-of-function of this variant is associated with a mild behavioral and neuropsychological phenotype.


Assuntos
Deficiência Intelectual , Mutação de Sentido Incorreto , Proteínas de Transporte/genética , Paralisia Cerebral , Proteínas de Ligação a DNA/genética , Humanos , Deficiência Intelectual/genética , Masculino , Herança Materna , Deficiência Intelectual Ligada ao Cromossomo X , Proteínas Nucleares/genética , Fenótipo , Precursores de RNA
18.
Psychon Bull Rev ; 28(1): 209-218, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32815113

RESUMO

Selective stopping is demanded in situations where responses must be suppressed to certain signals, but not others. To explore this type of inhibition, the standard stop-signal task has been modified to include a selective implementation of response inhibition by introducing a new stimulus that participants should ignore. However, a stimulus-selective stop-signal task can be performed following different strategies. Some participants fulfill the selective implementation of the stopping process after discriminating the stop and ignore signals, but some others stop the ongoing response whenever any new stimulus appears. The factors that influence this strategy choice are being explored, where both task and participant variables are under consideration. This study aimed to investigate whether the difficulty in discriminating between stop and ignore signals influences strategy adoption. Additionally, we examined whether participants modify their strategy in a flexible manner throughout the task in alternating easy and hard discrimination condition blocks. In the easy discrimination condition, the stop and the ignore signals differed both in color and shape, whereas in the hard discrimination condition, they only differed in shape. Our results from 64 participants revealed that manipulating the difficulty of signal discrimination strongly influenced strategy choice. Also, we found that participants can adapt their strategy according to task demands. They preferentially adopted a selective stopping strategy when discrimination was easy, whereas they changed to a nonselective stopping strategy under the hard discrimination condition. Overall, results from the current study suggest that signal discrimination difficulty influences the adoption of strategies in selective stopping.


Assuntos
Função Executiva/fisiologia , Inibição Psicológica , Desempenho Psicomotor/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
19.
Eur J Paediatr Neurol ; 35: 8-15, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34547584

RESUMO

KBG syndrome is characterized by dental, craniofacial and skeletal anomalies, short stature and global developmental delay or intellectual disability. It is caused by microdeletions or truncating mutations of ANKRD11. We report four unrelated probands with this syndrome due to de novo ANKRD11 aberrations that may contribute to a better understanding of the genetics and pathophysiology of this autosomal dominant syndrome. Clinical, cognitive and MRI assessments were performed. Three of the patients showed normal intellectual functioning, whereas the fourth had a borderline level of intellectual functioning. However, all of them showed deficits in various cognitive and socioemotional processes such as attention, executive functions, empathy or pragmatic language. Moreover, all probands displayed marked asymmetry of the uncinate fascicles and an abnormal gyrification pattern in the left frontal lobe. Thus, structural neuroimaging anomalies seem to have been overlooked in this syndrome. Disturbed frontal gyrification and/or lower structural integrity of the uncinate fascisulus might be unrecognized neuroimaging features of KBG syndrome caused by ANKRD11 aberrations. Present results also point out that this syndrome is not necessarily associated with global developmental delay and intellectual disability, but it can be related to other neurodevelopmental disorders or subclinical levels of attention-deficit hyperactivity disorder, autism, communication disorders or specific learning disabilities.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Proteínas Repressoras , Anormalidades Dentárias , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/genética , Fácies , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/genética , Fenótipo , Proteínas Repressoras/genética , Anormalidades Dentárias/diagnóstico por imagem , Anormalidades Dentárias/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-34200757

RESUMO

The main aim of this study was to investigate the development of selective inhibitory control in middle childhood, a critical period for the maturation of inhibition-related processes. To this end, 64 children aged 6-7 and 56 children aged 10-11 performed a stimulus-selective stop-signal task, which allowed us to estimate not only the efficiency of response inhibition (the stop-signal reaction time or SSRT), but also the strategy adopted by participants to achieve task demands. We found that the adoption of a non-selective (global) strategy characterized by stopping indiscriminately to all stimuli decreased in older children, so that most of them were able to interrupt their ongoing responses selectively at the end of middle childhood. Moreover, compared to younger children, older children were more efficient in their ability to cancel an initiated response (indexed by a shorter SSRT), regardless of which strategy they used. Additionally, we found improvements in other forms of impulsivity, such as the control of premature responding (waiting impulsivity), and attentional-related processes, such as intra-individual variability and distractibility. The present results suggest that middle childhood represents a milestone in the development of crucial aspects of inhibitory control, including selective stopping.


Assuntos
Comportamento Impulsivo , Inibição Psicológica , Adolescente , Atenção , Criança , Cognição , Humanos , Desempenho Psicomotor , Tempo de Reação
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