RESUMO
The corpus callosum, the largest white matter inter-hemispheric pathway, is involved in language and communication. In a cohort of 15 children and adolescents (8-15 years) with developmental absence of the corpus callosum (AgCC), this study aimed to describe language and everyday communication functioning, and explored the role of anatomical factors, social risk, and non-verbal IQ in these outcomes. Standardised measures of language and everyday communication functioning, intellectual ability and social risk were used. AgCC classification and anterior commissure volume, a potential alternative pathway, were extracted from T1-weighted images. Participants with AgCC showed reduced receptive and expressive language compared with test norms, and high rates of language and communication impairments. Complete AgCC, higher social risk and lower non-verbal IQ were associated with communication difficulties. Anterior commissure volume was not associated with language and communication. Recognising heterogeneity in language and communication functioning enhances our understanding and suggests specific focuses for potential interventions.
Assuntos
Agenesia do Corpo Caloso , Humanos , Adolescente , Criança , Masculino , Feminino , Agenesia do Corpo Caloso/fisiopatologia , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/complicações , Agenesia do Corpo Caloso/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/fisiopatologia , Corpo Caloso/patologia , Comunicação , Imageamento por Ressonância Magnética , Idioma , Transtornos da Comunicação/fisiopatologia , Transtornos da Comunicação/etiologia , Inteligência/fisiologiaRESUMO
OBJECTIVES: To evaluate the evolution of interhemispheric coherences (ICo) in background and spindle frequency bands during childhood and use it to identify individuals with corpus callosum dysgenesis (CCd). METHODS: A monocentric cohort of children aged from 0.25 to 15 years old, consisting of 13 children with CCd and 164 without, was analyzed. The ICo of background activity (ICOBckgrdA), sleep spindles (ICOspindles), and their sum (sICO) were calculated. The impact of age, gender, and CC status on the ICo was evaluated, and the sICO was used to discriminate children with or without CCd. RESULTS: ICOBckgrdA, ICOspindles and sICO increased significantly with age without any effect of gender (p < 10-4), in both groups. The regression equations of the different ICo were stronger, with adjusted R2 values of 0.54, 0.35, and 0.57, respectively. The ICo was lower in children with CCd compared to those without CCd (p < 10-4 for all comparisons). The area under the precision recall curves for predicting CCd using sICO was 0.992 with 98.9 % sensitivity and 87.5 % specificity. DISCUSSION: ICo of spindles and background activity evolve in parallel to brain maturation and depends on the integrity of the corpus callosum. sICO could be an effective diagnostic biomarker for screening children with interhemispheric dysfunction.
Assuntos
Agenesia do Corpo Caloso , Eletroencefalografia , Humanos , Criança , Masculino , Feminino , Pré-Escolar , Adolescente , Eletroencefalografia/métodos , Agenesia do Corpo Caloso/fisiopatologia , Agenesia do Corpo Caloso/diagnóstico , Lactente , Corpo Caloso/fisiopatologia , Estudos de Coortes , Ondas Encefálicas/fisiologiaRESUMO
ABSTRACT A 12-year-old boy with Donnai-Barrow syndrome diagnosed intra-uterus presented esotropia, high myopia, nystagmus, and optic disk staphyloma in an ophthalmologic examination. The patient had associated Fanconi syndrome and sensorineural hearing loss as well as facial manifestations as hypertelorism, downward slanting of palpebral fissures and low ear implantation. Magnetic resonance imaging revealed agenesis of the corpus callosum. To our knowledge, this is the first reported case associated with esotropia, nystagmus, and optic disk staphyloma.
RESUMO Paciente do sexo masculino, 12 anos, com diagnóstico intrauterino de síndrome de Donnai-Barrow, apresentava ao exame oftalmológico esotropia, alta miopia, nistagmo e estafiloma de disco óptico. Associado ao quadro, apresentava síndrome de Falconi e perda auditiva neurossensorial, além de alterações faciais, como hipertelorismo, inclinação inferior das fissuras palpebrais e implantação baixa das orelhas. Ressonância magnética revelou agenesia de corpo caloso. Ao nosso conhecimento, este é o primeiro caso relatado associando esotropia, nistagmo e estafiloma de disco óptico.
Assuntos
Humanos , Masculino , Criança , Anormalidades Múltiplas , Doenças do Nervo Óptico/fisiopatologia , Esotropia/fisiopatologia , Nistagmo Patológico/fisiopatologia , Miopia/fisiopatologia , Erros Inatos do Transporte Tubular Renal , Síndrome , Acidose Tubular Renal , Descolamento Retiniano , Criptorquidismo , Síndrome de Fanconi/fisiopatologia , Agenesia do Corpo Caloso/fisiopatologia , Hérnias Diafragmáticas Congênitas , Perda Auditiva Neurossensorial , Hipertelorismo/fisiopatologiaAssuntos
Agenesia do Corpo Caloso/complicações , Agenesia do Corpo Caloso/fisiopatologia , COVID-19/complicações , COVID-19/fisiopatologia , Progressão da Doença , Hiperidrose/complicações , Hiperidrose/fisiopatologia , Hipotermia/complicações , Hipotermia/fisiopatologia , Agenesia do Corpo Caloso/diagnóstico , COVID-19/diagnóstico , Feminino , Humanos , Hiperidrose/diagnóstico , Hipotermia/diagnóstico , Pessoa de Meia-IdadeRESUMO
Hereditary motor sensory neuropathy (HMSN/ACC) with agenesis of the corpus callosum (ACC) has been documented in the French-derived populations of Charlevoix and Saguenay/Lac St. Jean in Quebec, Canada, as well as a few sporadic families throughout the world. HMSN/ACC occurs because of loss-of-function mutations in the potassium-chloride cotransporter 3 (KCC3). In HMSN/ACC, motor deficits occur early in infancy with rapid and continual deterioration of motor and sensory fibers into juvenile and adulthood. Genetic work in mice has demonstrated that the disease is caused by loss of KCC3 function in neurons and particularly parvalbumin (PV)-expressing neurons. Currently, there are no treatments or cures for HMSN/ACC other than pain management. As genetic counseling in Quebec has increased as a preventative strategy, most individuals with HSMN/ACC are now adults. The onset of the disease is unknown. In particular, it is unknown if the disease starts early during development and whether it can be reversed by restoring KCC3 function. In this study, we used two separate mouse models that when combined to the PV-CreERT2 tamoxifen-inducible system allowed us to 1) disrupt KCC3 expression in adulthood or juvenile periods; and 2) reintroduce KCC3 expression in mice that first develop with a nonfunctional cotransporter. We show that disrupting or reintroducing KCC3 in the adult mouse has no effect on locomotor behavior, indicating that expression of KCC3 is critical during embryonic development and/or the perinatal period and that once the disease has started, reexpressing a functional cotransporter fails to change the course of HMSN/ACC.
Assuntos
Agenesia do Corpo Caloso/terapia , Comportamento Animal , Gânglios Espinais/metabolismo , Terapia Genética , Atividade Motora , Doenças do Sistema Nervoso Periférico/terapia , Simportadores/metabolismo , Fatores Etários , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/metabolismo , Agenesia do Corpo Caloso/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Gânglios Espinais/fisiopatologia , Regulação da Expressão Gênica no Desenvolvimento , Predisposição Genética para Doença , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Parvalbuminas/metabolismo , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Fenótipo , Equilíbrio Postural , Teste de Desempenho do Rota-Rod , Simportadores/genéticaAssuntos
Adenilossuccinato Liase/deficiência , Adenilossuccinato Liase/genética , Agenesia do Corpo Caloso/fisiopatologia , Transtorno Autístico/genética , Deficiências do Desenvolvimento/fisiopatologia , Epilepsia/fisiopatologia , Lisencefalia/fisiopatologia , Hipotonia Muscular/fisiopatologia , Erros Inatos do Metabolismo da Purina-Pirimidina/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Agenesia do Corpo Caloso/diagnóstico por imagem , Transtorno Autístico/diagnóstico , Transtorno Autístico/fisiopatologia , Vermis Cerebelar/anormalidades , Vermis Cerebelar/diagnóstico por imagem , Córtex Cerebral/anormalidades , Córtex Cerebral/diagnóstico por imagem , Eletroencefalografia , Heterozigoto , Humanos , Recém-Nascido , Lisencefalia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Mutação , Tamanho do Órgão , Erros Inatos do Metabolismo da Purina-Pirimidina/diagnóstico , Erros Inatos do Metabolismo da Purina-Pirimidina/fisiopatologia , Sequenciamento do ExomaAssuntos
Agenesia do Corpo Caloso , Perda Auditiva Neurossensorial , Hérnias Diafragmáticas Congênitas , Túbulos Renais , Miopia , Proteinúria , Erros Inatos do Transporte Tubular Renal , Agenesia do Corpo Caloso/fisiopatologia , Perda Auditiva Neurossensorial/fisiopatologia , Hérnias Diafragmáticas Congênitas/fisiopatologia , Humanos , Túbulos Renais/fisiopatologia , Miopia/fisiopatologia , Nefrologistas , Proteinúria/fisiopatologia , Erros Inatos do Transporte Tubular Renal/fisiopatologiaRESUMO
The present study is interested in the role of the corpus callosum in the development of the language network. We, therefore, investigated language abilities and the language network using task-based fMRI in three cases of complete agenesis of the corpus callosum (ACC), three cases of partial ACC and six controls. Although the children with complete ACC revealed impaired functions in specific language domains, no child with partial ACC showed a test score below average. As a group, ACC children performed significantly worse than healthy controls in verbal fluency and naming. Furthermore, whole-brain ROI-to-ROI connectivity analyses revealed reduced intrahemispheric and right intrahemispheric functional connectivity in ACC patients as compared to controls. In addition, stronger functional connectivity between left and right temporal areas was associated with better language abilities in the ACC group. In healthy controls, no association between language abilities and connectivity was found. Our results show that ACC is associated not only with less interhemispheric, but also with less right intrahemispheric language network connectivity in line with reduced verbal abilities. The present study, thus, supports the excitatory role of the corpus callosum in functional language network connectivity and language abilities.
Assuntos
Cognição/fisiologia , Corpo Caloso/fisiologia , Lateralidade Funcional/fisiologia , Idioma , Adolescente , Agenesia do Corpo Caloso/fisiopatologia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
The corpus callosum is the largest white matter pathway in the brain connecting the two hemispheres. In the context of developmental absence (agenesis) of the corpus callosum (AgCC), a proposed candidate for neuroplastic response is strengthening of intrahemispheric pathways. To test this hypothesis, we assessed structural and functional connectivity in a uniquely large cohort of children with AgCC (n = 20) compared with typically developing controls (TDC, n = 29), and then examined associations with neurobehavioral outcomes using a multivariate data-driven approach (partial least squares correlation, PLSC). For structural connectivity, children with AgCC showed a significant increase in intrahemispheric connectivity in addition to a significant decrease in interhemispheric connectivity compared with TDC, in line with the aforementioned hypothesis. In contrast, for functional connectivity, children with AgCC and TDC showed a similar pattern of intrahemispheric and interhemispheric connectivity. In conclusion, we observed structural strengthening of intrahemispheric pathways in children born without corpus callosum, which seems to allow for functional connectivity comparable to a typically developing brain, and were relevant to explain neurobehavioral outcomes in this population. This neuroplasticity might be relevant to other disorders of axonal guidance, and developmental disorders in which corpus callosum alteration is observed.
Assuntos
Agenesia do Corpo Caloso/fisiopatologia , Comportamento Infantil/fisiologia , Corpo Caloso/fisiologia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Adolescente , Agenesia do Corpo Caloso/diagnóstico por imagem , Criança , Comportamento Infantil/psicologia , Estudos de Coortes , Corpo Caloso/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/diagnóstico por imagemRESUMO
Aicardi syndrome (AIC) is a rare congenital neurodevelopmental disorder of unknown etiology, that affects almost exclusively females, originally characterized by corpus callosum agenesis, chorioretinal lacunae, and infantile spasms. The current diagnostic criteria also include qualitative facial features (prominent premaxilla, upturned nasal tip, decreased nasal bridge angle, sparse lateral eyebrows, and microphthalmia) that still need quantification. A three-dimensional (3D) photogrammetric assessment of 11 Italian females, age 7-32 years, who satisfied AIC criteria, was performed. Linear distances and angles were computed from soft-tissue facial landmarks coordinates. The z-score values were calculated using data of 850 healthy reference females matched for age and compared by Mann-Whitney test (p < .01). Patients showed a shorter philtrum and right side orbital height (mean z-scores: -1.7, -0.9), shorter superior, middle, and inferior facial depths (mean z-scores: -1.3, -2.2, -2.3), and a smaller length of mandibular ramus (mean z-score: -2.1); conversely, they showed larger nasal and lower facial widths, and lower facial convexity (mean z-scores: 1.7, 1.4, 2.4). The inclinations of the orbit versus the true horizontal were increased bilaterally (mean z-scores: 1.8, 1.1). Some common facial abnormalities were quantified in AIC patients using a noninvasive instrument. They may help clinicians in performing a definite AIC diagnosis in atypical or doubt cases.
Assuntos
Síndrome de Aicardi/diagnóstico , Face/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Adolescente , Adulto , Agenesia do Corpo Caloso/diagnóstico , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/fisiopatologia , Síndrome de Aicardi/diagnóstico por imagem , Síndrome de Aicardi/fisiopatologia , Pesos e Medidas Corporais , Criança , Síndrome de Down/diagnóstico por imagem , Síndrome de Down/genética , Síndrome de Down/fisiopatologia , Face/fisiopatologia , Feminino , Humanos , Itália/epidemiologia , Nariz/diagnóstico por imagem , Nariz/fisiopatologia , Adulto JovemRESUMO
Corpus callosum dysgenesis (CCD) is a developmental brain condition in which some white matter fibers fail to find their natural course across the midplane, reorganizing instead to form new aberrant pathways. This type of white matter reorganization is known as long-distance plasticity (LDP). The present work aimed to characterize the Balb/c mouse strain as a model of CCD. We employed high-resolution anatomical MRI in 81 Balb/c and 27 C57bl6 mice to show that the Balb/c mouse strain presents a variance in the size of the CC that is 3.9 times higher than the variance of normotypical C57bl6. We also performed high-resolution diffusion-weighted imaging (DWI) in 8 Balb/c and found that the Balb/c strain shows aberrant white matter bundles, such as the Probst (5/8 animals) and the Sigmoid bundles (7/8 animals), which are similar to those found in humans with CCD. Using a histological tracer technique, we confirmed the existence of these aberrant bundles in the Balb/c strain. Interestingly, we also identified sigmoid-like fibers in the C57bl6 strain, thought to a lesser degree. Next, we used a connectome approach and found widespread brain connectivity differences between Balb/c and C57bl6 strains. The Balb/c strain also exhibited increased variability of global connectivity. These findings suggest that the Balb/c strain presents local and global changes in brain structural connectivity. This strain often presents with callosal abnormalities, along with the Probst and the Sigmoid bundles, making it is an attractive animal model for CCD and LDP in general. Our results also show that even the C57bl6 strain, which typically serves as a normotypical control animal in a myriad of studies, presents sigmoid-fashion pattern fibers laid out in the brain. These results suggest that these aberrant fiber pathways may not necessarily be a pathological hallmark, but instead an alternative roadmap for misguided axons. Such findings offer new insights for interpreting the significance of CCD-associated LDP in humans.
Assuntos
Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/fisiopatologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Animais , Conectoma , Corpo Caloso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fibras Nervosas Mielinizadas/patologia , Especificidade da Espécie , Substância Branca/diagnóstico por imagemRESUMO
INTRODUCTION: Whole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies. OBJECTIVE: To discover novel genes linked to both CC anomalies and NDD. METHODS: Clinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in SUPT16H, a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared. RESULTS: We identified four patients with de novo missense variants in SUPT16H and one patient with a de novo deletion including SUPT16H. These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging. CONCLUSION: Our findings implicate the gene SUPT16H in a novel disorder characterised by neurodevelopmental deficits and CC anomalies.
Assuntos
Agenesia do Corpo Caloso/genética , Proteínas de Ciclo Celular/genética , Predisposição Genética para Doença , Transtornos do Neurodesenvolvimento/genética , Fatores de Transcrição/genética , Adolescente , Agenesia do Corpo Caloso/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Corpo Caloso/fisiopatologia , Exoma/genética , Feminino , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Masculino , Mutação de Sentido Incorreto/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , Convulsões/genética , Convulsões/fisiopatologia , Sequenciamento do ExomaRESUMO
The purpose of this article is to report a case study of the effect of therapeutic drumming on motor, communication skills, and behavior of a preteen diagnosed with agenesis of the corpus callosum. This 12-year-old participated in 30- to 45-minute weekly sessions over a 12-month period in which rudimentary drumming exercises were used to analyze and then measure any changes in equilibrium reactions, postural transfers, and trunk control. Measurable documentation evidenced marked improvement in motor skills while suggesting communication and behavioral improvement. The findings support the theory that therapeutic drumming would benefit preteens with agenesis of the corpus callosum, which provides promising evidence to other neurologic developmental diagnoses and therefore indicates a need for further research. While the therapeutic nature of music is well documented, how the listener participates can influence the effect of the music. For example, passive music listening can improve pain or anxiety, however, active music listening with expected intentional action may improve physical, mental, behavioral, and spiritual healing. Active music listening could be a valuable holistic nursing intervention.
Assuntos
Agenesia do Corpo Caloso/terapia , Musicoterapia/normas , Agenesia do Corpo Caloso/fisiopatologia , Criança , Emoções/fisiologia , Feminino , Humanos , Força Muscular/fisiologia , Musicoterapia/métodos , Musicoterapia/estatística & dados numéricos , Resistência Física/fisiologia , Equilíbrio Postural/fisiologia , Propriocepção/fisiologia , Desempenho Psicomotor/fisiologiaRESUMO
Mutations in MED12 gene have been described in association with syndromic and non-syndromic X-linked intellectual disability (XLID). Up to date at least three distinct XLID syndromes have been described: FG syndrome, Lujan-Fryns syndrome (LS) and Ohdo syndrome (OSMKB). In the last years, thanks to the massive use of next generation sequencing techniques (NGS) it has been possible to discover at least 16 others MED12 mutations and to expand the phenotype of MED12-related disorders. Here we report three subjects from a large non-consanguineous family presenting with a mild to severe ID, important speech delay, behavior problems, dysmorphic facial features and hearing loss. NGS allows us to detect the MED12 missense variant c.3883Câ¯>â¯T (p.(Arg1295Cys)) carried by the three patients. This variant has been reported in 2016 by Hu et al. in one family from a big cohort of XLID families. This clinical report contributes to expanding the phenotype associated with MED12-mutations.
Assuntos
Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/genética , Anus Imperfurado/genética , Blefarofimose/genética , Blefaroptose/genética , Constipação Intestinal/genética , Anormalidades Craniofaciais/genética , Cardiopatias Congênitas/genética , Deficiência Intelectual/genética , Síndrome de Marfan/genética , Complexo Mediador/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Hipotonia Muscular/congênito , Anormalidades Múltiplas/fisiopatologia , Adolescente , Agenesia do Corpo Caloso/fisiopatologia , Anus Imperfurado/fisiopatologia , Blefarofimose/fisiopatologia , Blefaroptose/fisiopatologia , Criança , Constipação Intestinal/fisiopatologia , Anormalidades Craniofaciais/fisiopatologia , Genes Ligados ao Cromossomo X , Perda Auditiva/genética , Perda Auditiva/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Síndrome de Marfan/fisiopatologia , Deficiência Intelectual Ligada ao Cromossomo X/fisiopatologia , Pessoa de Meia-Idade , Hipotonia Muscular/genética , Hipotonia Muscular/fisiopatologia , Mutação de Sentido Incorreto , LinhagemRESUMO
Agenesis of the corpus callosum (ACC) is a common prenatally-detected brain anomaly. Recently, an association between mutations in the DCC Netrin 1 receptor (DCC) gene and ACC, with or without mirror movements, has been demonstrated. In this manuscript, we present a family with a novel heterozygous frameshift mutation in DCC, review the available literature, and discuss the challenges involved in the genetic counseling for recently discovered disorders with paucity of medical information. We performed whole exome sequencing in a healthy nonconsanguineous couple that underwent two pregnancy terminations due to prenatal diagnosis of ACC. A heterozygous variant c.2774dupA (p.Asn925Lysfs*17) in the DCC gene was demonstrated in fetal and paternal DNA samples, as well as in a healthy 4-year-old offspring. When directly questioned, both father and child reported having mirror movements not affecting quality of life. Segregation analysis demonstrated the variant in three paternal siblings, two of them having mirror movements. Brain imaging revealed normal corpus callosum. Summary of literature data describing heterozygous loss-of-function variants in DCC (n = 61) revealed 63.9% penetrance for mirror movements, 9.8% for ACC, and 5% for both. No significant neurodevelopmental abnormalities were reported among the seven published patients with DCC loss-of-function variants and ACC. Prenatal diagnosis of ACC should prompt a specific anamnesis regarding any neurological disorder, as well as intentional physical examination of both parents aimed to detect mirror movements. In suspicious cases, detection of DCC pathogenic variants might markedly improve the predicted prognosis, alleviate the parental anxiety, and possibly prevent pregnancy termination.
Assuntos
Agenesia do Corpo Caloso/genética , Receptor DCC/genética , Transtornos dos Movimentos/genética , Malformações do Sistema Nervoso/genética , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/fisiopatologia , Feminino , Aconselhamento Genético , Heterozigoto , Humanos , Masculino , Transtornos dos Movimentos/diagnóstico por imagem , Transtornos dos Movimentos/fisiopatologia , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/fisiopatologia , Penetrância , Gravidez , Diagnóstico Pré-NatalRESUMO
Agenesis of the corpus callosum is a congenital brain malformation that can occur in isolation or as a component of a congenital syndrome. Hepatoblastoma (HB) is a rare tumor that comprises two thirds of primary hepatic neoplasms in children and adolescents. Up to 20% of children with HB have associated congenital anomalies. In addition to defined genetic syndromes such as Familial Adenomatous Polyposis, Beckwith-Wiedemann syndrome, Trisomy 13, and Trisomy 18, HB is significantly associated with kidney/bladder abnormalities. We present two children with multiple congenital anomalies, including agenesis of the corpus callosum, who were subsequently diagnosed with HB. Review of the literature revealed two patients with clinically-diagnosed Aicardi syndrome and HB. Due to the rarity of both agenesis of the corpus callosum and HB, this is likely a true association. Further investigation into the underlying genetic and molecular basis of this probable association is warranted.
Assuntos
Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/genética , Síndrome de Aicardi/genética , Hepatoblastoma/genética , Anormalidades Múltiplas/fisiopatologia , Agenesia do Corpo Caloso/complicações , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/fisiopatologia , Síndrome de Aicardi/complicações , Síndrome de Aicardi/diagnóstico por imagem , Síndrome de Aicardi/fisiopatologia , Criança , Pré-Escolar , Corpo Caloso/fisiopatologia , Feminino , Hepatoblastoma/complicações , Hepatoblastoma/diagnóstico por imagem , Hepatoblastoma/fisiopatologia , Humanos , Lactente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologiaRESUMO
In the absence of the corpus callosum due to either surgical transection or congenital agenesis, the interhemispheric exchange of information is disrupted, as emphasized by several clinical studies. In such cases, a reduction of interhemispheric functional connectivity, that is, an increased independence of the functional signals of the two disconnected hemispheres, is expected to occur. A growing literature has investigated this hypothesis, and a number of studies were able to confirm it. However, this increased independence is not always observed, especially in congenital agenesis, in which the functional signals of the two hemispheres are often found to be characterized by synchronization or correlation. The extent of these counterintuitive findings and possible explanations are discussed. Overall, these findings highlight both methodological and theoretical considerations that emphasize the importance of subcortical structures, the preservation of which may underlie alternative pathways of functional connectivity and interhemispheric communication.
Assuntos
Agenesia do Corpo Caloso/fisiopatologia , Encéfalo/fisiopatologia , Conectoma , Corpo Caloso/fisiopatologia , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Agenesia do Corpo Caloso/patologia , Encéfalo/patologia , Corpo Caloso/patologia , Corpo Caloso/cirurgia , Humanos , Rede Nervosa/patologia , Vias Neurais/patologiaRESUMO
BACKGROUND: Vici syndrome is a neurodevelopmental disorder of the autophagy pathway. Almost all cases reported have the cardinal features of agenesis of corpus callosum, cataract, cardiomyopathy, immunodeficiency and hypopigmentation. CASE CHARACTERISTICS: 8-month-old boy with developmental delay, myoclonic jerks, repeated respiratory infections, coarse facial features, cataract and hypopigmented hair. Echocardiography revealed dilated cardiomyopathy and magnetic resonance imaging of brain suggested agenesis of corpus callosum. Exome sequencing detected a novel homozygous nonsense mutation in the EPG5 gene. OUTCOME: Establishing a definite diagnosis helped in proper prognostication, providing genetic counseling and prenatal diagnosis to the family. MESSAGE: Though uncommon, presence of the characteristic features makes Vici syndrome a clinically recognizable cause of developmental delay.
Assuntos
Agenesia do Corpo Caloso , Proteínas Relacionadas à Autofagia/genética , Encéfalo/diagnóstico por imagem , Catarata , Deficiências do Desenvolvimento , Doenças por Armazenamento dos Lisossomos/diagnóstico , Proteínas de Transporte Vesicular/genética , Assistência ao Convalescente/métodos , Agenesia do Corpo Caloso/diagnóstico , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/fisiopatologia , Catarata/diagnóstico , Catarata/genética , Catarata/fisiopatologia , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Diagnóstico Diferencial , Testes Genéticos , Humanos , Síndromes de Imunodeficiência/diagnóstico , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Mutação , IrmãosAssuntos
Agenesia do Corpo Caloso/diagnóstico por imagem , Cistos/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Imageamento por Ressonância Magnética , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/fisiopatologia , Cistos/congênito , Cistos/patologia , Diagnóstico Tardio , Deficiências do Desenvolvimento/fisiopatologia , Humanos , Lactente , Masculino , Neuroimagem , PrognósticoRESUMO
The paradoxical absence of a split-brain syndrome in most cases of callosal dysgenesis has originated three main hypotheses, namely, (i) bilateral cortical representation of language, (ii) bilateral thalamocortical projections of somatosensory pathways conveyed by the spinothalamic-medial lemniscus system, and (iii) a variable combination of (i) and (ii). We used functional neuroimaging to investigate the cortical representation and lateralization of somatosensory information from the palm of each hand in six cases of callosal dysgenesis (hypothesis [ii]). Cortical regions of interest were contralateral and ipsilateral S1 (areas 3a and 3b, 1 and 2 in the central sulcus and postcentral gyrus) and S2 (parts of areas 40 and 43 in the parietal operculum). The degree of cortical asymmetry was expressed by a laterality index (LI), which may assume values from -1 (fully left-lateralized) to +1 (fully right-lateralized). In callosal dysgenesis, LI values for the right and the left hands were, respectively, -1 andâ¯+â¯1 for both S1 and S2, indicating absence of engagement of ipsilateral S1 and S2. In controls, LI values wereâ¯-â¯0.70 (S1) andâ¯-â¯0.51 (S2) for right hand stimulation, and 0.82 (S1) and 0.36 (S2) for left hand stimulation, reflecting bilateral asymmetric activations, which were significantly higher in the hemisphere contralateral to the stimulated hand. Therefore, none of the main hypotheses so far entertained to account for the callosal dysgenesis-split-brain paradox have succeeded. We conclude that the preserved interhemispheric transfer of somatosensory tactile information in callosal dysgenesis must be mediated by a fourth alternative, such as aberrant interhemispheric bundles, reorganization of subcortical commissures, or both.