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2.
Neurology ; 95(6): e718-e732, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32518148

RESUMO

OBJECTIVE: To characterize the extent of CNS involvement in children with Pompe disease using brain MRI and developmental assessments. METHODS: The study included 14 children (ages 6-18 years) with infantile Pompe disease (IPD) (n = 12) or late-onset Pompe disease (LOPD) (n = 2) receiving enzyme replacement therapy. White matter (WM) hyperintense foci seen in the brain MRIs were systematically quantified using the Fazekas scale (FS) grading system with a novel approach: the individual FS scores from 10 anatomical areas were summed to yield a total FS score (range absent [0] to severe [30]) for each child. The FS scores were compared to developmental assessments of cognition and language obtained during the same time period. RESULTS: Mild to severe WM hyperintense foci were seen in 10/12 children with IPD (median age 10.6 years) with total FS scores ranging from 2 to 23. Periventricular, subcortical, and deep WM were involved. WM hyperintense foci were seen throughout the path of the corticospinal tracts in the brain in children with IPD. Two children with IPD had no WM hyperintense foci. Children with IPD had relative weaknesses in processing speed, fluid reasoning, visual perception, and receptive vocabulary. The 2 children with LOPD had no WM hyperintense foci, and high scores on most developmental assessments. CONCLUSION: This study systematically characterized WM hyperintense foci in children with IPD, which could serve as a benchmark for longitudinal follow-up of WM abnormalities in patients with Pompe disease and other known neurodegenerative disorders or leukodystrophies in children.


Assuntos
Encefalopatias Metabólicas Congênitas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Doença de Depósito de Glicogênio Tipo II/diagnóstico por imagem , Imagem por Ressonância Magnética , Neuroimagem , Adolescente , Idade de Início , Encéfalo/patologia , Encefalopatias Metabólicas Congênitas/etiologia , Criança , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Estudos Transversais , Deficiências do Desenvolvimento/etiologia , Terapia de Reposição de Enzimas , Glucana 1,4-alfa-Glucosidase/uso terapêutico , Doença de Depósito de Glicogênio Tipo II/complicações , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Doença de Depósito de Glicogênio Tipo II/psicologia , Humanos , Transtornos da Linguagem/diagnóstico por imagem , Transtornos da Linguagem/etiologia , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Substância Branca/diagnóstico por imagem
3.
J Clin Ultrasound ; 48(4): 240-243, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31994200

RESUMO

We report the case of a fetus with sonographic characteristics of Beckwith-Wiedemann syndrome (BWS). A 30-year-old gravida 2 para 1 was referred to our fetal medicine unit with an omphalocele. Fetal macrosomia, organomegaly, and polyhydramnios but no macroglossia were detected and BWS was suspected. Genetic testing for BWS did not confirm the suspected diagnosis as the karyotype was normal. Symptomatic polyhydramnios led to repeated amnioreductions. At 35 + 5 weeks of gestation, a female neonate of 3660 g was delivered with APGAR scores of 6/7/8, after 1/5/10 min, respectively. The abnormal shape of the thorax, facial dysmorphism, need for ventilation, and generalized muscular hypotonia led to the suspicion of Kagami-Ogata syndrome (KOS), which was confirmed by genetic testing. KOS in our patient was caused by a large deletion in the MEG3-region on chromosome 14q32 affecting the maternal allele. In this report, we highlight the notion that when sonographic signs suggestive of BWS such as macrosomia, polyhydramnios, and omphalocele are present and genetic testing does not confirm the suspected diagnosis, KOS should be tested for.


Assuntos
Síndrome de Beckwith-Wiedemann/diagnóstico por imagem , Transtornos Cromossômicos/diagnóstico por imagem , Anormalidades Craniofaciais/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Hérnia Umbilical/diagnóstico por imagem , Poli-Hidrâmnios/diagnóstico por imagem , Dissomia Uniparental/patologia , Adulto , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 14/genética , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Diagnóstico Diferencial , Feminino , Idade Gestacional , Hérnia Umbilical/genética , Humanos , Recém-Nascido , Poli-Hidrâmnios/genética , Gravidez , Ultrassonografia Pré-Natal , Dissomia Uniparental/genética
4.
J Pediatr ; 217: 79-85.e1, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31706634

RESUMO

OBJECTIVE: To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in 2008-2013. STUDY DESIGN: Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2 years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate. RESULTS: We enrolled 160 infants with median gestational age of 26.6 weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2 years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P = .6). Increasing PVHI severity score was associated with death (P < .001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P = .01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P = .004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P < .001 for both). CONCLUSIONS: Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Doenças do Prematuro/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/patologia , Infarto Cerebral/mortalidade , Infarto Cerebral/patologia , Paralisia Cerebral/complicações , Ventrículos Cerebrais/patologia , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Doenças do Prematuro/patologia , Masculino , Estudos Retrospectivos , Ultrassonografia
6.
Elife ; 82019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31843053

RESUMO

Social visual engagement difficulties are hallmark early signs of autism (ASD) and are easily quantified using eye tracking methods. However, it is unclear how these difficulties are linked to atypical early functional brain organization in ASD. With resting state fMRI data in a large sample of ASD toddlers and other non-ASD comparison groups, we find ASD-related functional hypoconnnectivity between 'social brain' circuitry such as the default mode network (DMN) and visual and attention networks. An eye tracking-identified ASD subtype with pronounced early social visual engagement difficulties (GeoPref ASD) is characterized by marked DMN-occipito-temporal cortex (OTC) hypoconnectivity. Increased DMN-OTC hypoconnectivity is also related to increased severity of social-communication difficulties, but only in GeoPref ASD. Early and pronounced social-visual circuit hypoconnectivity is a key underlying neurobiological feature describing GeoPref ASD and may be critical for future social-communicative development and represent new treatment targets for early intervention in these individuals.


Assuntos
Transtorno Autístico/fisiopatologia , Movimentos Oculares/fisiologia , Rede Nervosa/fisiopatologia , Vias Neurais/fisiologia , Comportamento Social , Atenção/fisiologia , Transtorno Autístico/classificação , Transtorno Autístico/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Modelos Neurológicos
7.
Semin Pediatr Neurol ; 32: 100766, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31813522

RESUMO

Neuroimaging enables the evaluation of many aspects of brain maturation, and detection of abnormalities such as malformation and injury. MRI is integral to the diagnostic work-up of congenital and acquired disorders of the central nervous system in newborns, and imaging findings are central to prognostication. This paper reviews techniques to optimize assessment of maturity of the neonatal brain, as well as abnormalities and injuries of the newborn brain that are associated with abnormal neurocognitive development.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/anormalidades , Encefalopatias/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Humanos , Recém-Nascido , Imagem por Ressonância Magnética , Neuroimagem
8.
Sci Rep ; 9(1): 19072, 2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836837

RESUMO

The role of enlarged subarachnoid space (ESS) in preterm infants has not been described in concrete. We aimed to evaluate whether ESS should be considered a risk factor potentially associated with adverse neurodevelopmental outcomes in prematurity. Electronic medical records of 197 preterm infants (median 32.1 weeks' gestation) including cranial ultrasound (cUS) images, head circumferences, and Korean Developmental Screening Tests for Infants and Children (K-DST) results at 18-24 months corrected age were reviewed. The clinical characteristics and K-DST results were compared in infants with and without ESS (sinocortical width > 3.5 mm). A multivariable logistic regression analysis was performed to identify potential risk factors associated with positive K-DST results. At a median corrected age of 39.0 weeks, 81/197 (41.1%) infants presented ESS. A significantly greater percent of infants in the ESS group screened positive on the K-DST than in the no ESS group (27.2% vs 12.1%, p = 0.007). Within the ESS group, micro-/macrocephaly at term-equivalent age was not different with regard to the K-DST results. From the multivariable logistic regression analysis, gestational age (p = 0.016, OR = 0.855, 95% CI = 0.753-0.971) and ESS (p = 0.019, OR = 1.310, 95% CI = 1.046-1.641) were two significant risk factors associated with positive K-DST results. ESS identified on cUS at term-equivalent age in preterm infants is associated with possible developmental delays. Macrocephaly at term-equivalent age does not guarantee a benign prognosis. Future studies are required to verify ESS as a potential marker for neurodevelopmental delay in preterm infants.


Assuntos
Deficiências do Desenvolvimento/diagnóstico por imagem , Recém-Nascido Prematuro/fisiologia , Crânio/diagnóstico por imagem , Espaço Subaracnóideo/diagnóstico por imagem , Ultrassonografia , Humanos , Recém-Nascido , Masculino , Análise Multivariada
9.
Neuromuscul Disord ; 29(12): 930-939, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31708335

RESUMO

Little is known about the relationship between Becker Muscular Dystrophy (BMD) and mental disorders. This study aimed to clarify whether BMD is a risk factor for psychiatric diseases. We asked genetically or immunohistochemically confirmed BMD patients to participate in the study interview. Participants who consented to psychiatric tests underwent further assessments of intellectual, psychological, and neurodevelopmental disorders. In total, 76 (73%) of 105 BMD patients (median age, 37 years) completed the interview. Of these, 6 had developmental disorders (mental retardation, pervasive developmental disorder), 33/76 (43%) experienced bullying in school, 11 exhibited problematic behaviors such as cutting class and violent incidents, and 16 had psychiatric disorders (schizophrenia spectrum, 5; depressive spectrum, 4; stress-related disorders, 3; obsessive-compulsive and related disorders, 2; somatic symptom and related disorders, 2; bipolar and related disorders, 1). Mean IQ was normal, whereas 13/40 (32.5%) of participants were in a depressive state. High trait anxiety was found in 20/40 (50%) of patients, while 15/40 (38.5%) were in an anxious state. Review of MRI data from 14 participants revealed brain atrophy caused solely by BMD and unrelated to any other complication. Our findings suggest that BMD patients are at risk of developing psychiatric disorders. Physical handicap or bullying may influence their mental state, as many of them have high trait anxiety. Parents, teachers, and supporters should be mindful of the daily environment of BMD patients and provide support to help them cope with stress.


Assuntos
Deficiências do Desenvolvimento , Transtornos Mentais , Distrofia Muscular de Duchenne/psicologia , Adolescente , Adulto , Idoso , Atrofia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Bullying , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/epidemiologia , Humanos , Masculino , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/epidemiologia , Fatores de Risco , Adulto Jovem
10.
Mol Genet Metab ; 128(4): 452-462, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31727539

RESUMO

Lethal neonatal encephalopathies are heterogeneous congenital disorders that can be caused by mitochondrial dysfunction. Biallelic large deletions in the contiguous ATAD3B and ATAD3A genes, encoding mitochondrial inner membrane ATPases of unknown function, as well as compound heterozygous nonsense and missense mutations in the ATAD3A gene have been recently associated with fatal neonatal cerebellar hypoplasia. In this work, whole exome sequencing (WES) identified the novel homozygous variant c.1217 T > G in ATAD3A, predicting a p.(Leu406Arg) substitution, in four siblings from a consanguineous family presenting with fatal neonatal cerebellar hypoplasia, seizures, axial hypotonia, hypertrophic cardiomyopathy, hepatomegaly, congenital cataract, and dysmorphic facies. Biochemical phenotypes of the patients included hyperlactatemia and hypocholesterolemia. Healthy siblings and parents were heterozygous for this variant, which is predicted to introduce a polar chain within the catalytic domain of ATAD3A that shortens its beta-sheet structure, presumably affecting protein stability. Accordingly, patient's fibroblasts with the homozygous variant displayed a specific reduction in ATAD3A protein levels associated with profound ultrastructural alterations of mitochondrial cristae and morphology. Our findings exclude the causative role of ATAD3B on this severe phenotype, expand the phenotypical spectrum of ATAD3A pathogenic variants and emphasize the vital role of ATAD3A in mitochondrial biogenesis.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Cerebelo/anormalidades , Genes Recessivos , Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Mutação , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , ATPases Associadas a Diversas Atividades Celulares/química , Alelos , Substituição de Aminoácidos , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Proteínas de Membrana/química , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas Mitocondriais/química , Modelos Moleculares , Malformações do Sistema Nervoso/diagnóstico por imagem , Linhagem , Conformação Proteica , Relação Estrutura-Atividade , Ultrassonografia/métodos , Sequenciamento Completo do Exoma
11.
Pediatr Neurol ; 101: 39-42, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31495662

RESUMO

AIM: We aimed to characterize the phenotype and outcome of children with bilateral, large vessel perinatal arterial ischemic stroke. METHODS: Patients with bilateral, large vessel perinatal arterial ischemic stroke were identified from a large, population-based cohort (Alberta Perinatal Stroke Project). Subjects were included if stroke involving a major cerebral artery territory was documented in both cerebral hemispheres on magnetic resonance imaging. Standardized variables were extracted from charts including clinical presentations, associated potential risk factors, and outcomes. Outcome measures included the Pediatric Stroke Outcome Measure, Gross Motor Function Classification System, and epilepsy frequency score. Electroencephalographies were reviewed for sleep, epileptiform activity, and background. RESULTS: Of 174 children with perinatal arterial ischemic stroke, eight (5%) had bilateral large artery infarcts. Patients were followed for a mean of 9.7 years (range 1.8 to 14.6 years). One child died. All children had a total Pediatric Stroke Outcome Measure of ≥2 (median 8, range 2 to 10) and Gross Motor Function Classification System ≥ II. Seven of eight (88%) children had a history of epilepsy. CONCLUSIONS: Children with bilateral, large vessel perinatal stroke are at high risk of severe cognitive and motor sequelae. Epilepsy may also be more common than unilateral strokes. Cautious discussions with families regarding prognosis are recommended.


Assuntos
Isquemia Encefálica/complicações , Isquemia Encefálica/psicologia , Deficiências do Desenvolvimento/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Isquemia Encefálica/diagnóstico por imagem , Criança , Desenvolvimento Infantil , Pré-Escolar , Cognição , Estudos de Coortes , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Masculino , Destreza Motora , Acidente Vascular Cerebral/diagnóstico por imagem
12.
Mol Genet Genomic Med ; 7(9): e926, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397114

RESUMO

BACKGROUND: The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that lowers seizure threshold and may also enhance epileptogenesis. In this study, three patients diagnosed with SZT2-related developmental and epileptic encephalopathies (DEEs) were reviewed aiming to expand knowledge of the genotype and phenotype of SZT2 mutations. METHODS: Targeted next-generation sequencing was performed to identify pathogenic mutations in 205 cases with DEEs of unknown etiology. Detailed clinical and genetic data were collected from SZT2-associated patients. RESULTS: Four novel mutations were found (c.1626 + 1G>A, c.5772dupA, c.4209C > A, c.7307_7308insG) in three patients. All the variants were inherited from their parents. Two patients were siblings and harbored the same mutations and presented developmental delay prior to the onset of seizures. All the individuals were diagnosed as DEEs, drug refractory epilepsy, and experienced status epilepticus (SE); one patient died of SE. One subject showed subependymal nodules as similar as those of tuberous sclerosis complex (TSC) in cranial magnetic resonance imaging (MRI). CONCLUSION: Our results expand the genotype and phenotypes of SZT2-related DEEs, suggesting that SZT2 mutations play a role in developmental delay and epileptic encephalopathy, with high susceptibility to SE and relatively specific MRI findings.


Assuntos
Encefalopatias/genética , Deficiências do Desenvolvimento/genética , Mutação , Proteínas do Tecido Nervoso/genética , Estado Epiléptico/genética , Encefalopatias/diagnóstico por imagem , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Estado Epiléptico/diagnóstico por imagem
14.
Handb Clin Neurol ; 162: 201-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31324311

RESUMO

As magnetic resonance imaging has been increasingly used to study brain injury and brain development in premature newborns, the prevalence of cerebellar abnormalities is increasingly recognized. The preterm cerebellum is highly vulnerable to a number of insults during its critical phase of growth and development throughout the period of prematurity and beyond. Direct cerebellar injury and additional factors such as supratentorial brain injury and glucocorticoid exposure adversely impact cerebellar growth and, consequently, increase the risk of neurodevelopmental disabilities. In this chapter the causes and consequences of cerebellar hypoplasia of prematurity are reviewed.


Assuntos
Doenças Cerebelares/congênito , Doenças Cerebelares/patologia , Cerebelo/anormalidades , Doenças do Prematuro/patologia , Malformações do Sistema Nervoso/patologia , Adulto , Animais , Doenças Cerebelares/etiologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Imagem por Ressonância Magnética , Malformações do Sistema Nervoso/diagnóstico por imagem , Gravidez
15.
Can J Neurol Sci ; 46(6): 760-761, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31352912

RESUMO

A 9-year-old female presented to neurology outpatient department of our hospital with complaints of recurrent generalized tonic-clonic seizures since birth and was being treated with anticonvulsants for the same. Patient also had complaints of giddiness and episodes of momentary loss of consciousness. There was history of twitching of left hemiface and eyelid during infancy, often associated with deviation of eyes to the left and groaning. The birth history was unremarkable. Family history revealed no known consanguinity. General examination revealed no dysmorphic features. Neurological examination revealed no cognitive deficits/signs to suggest cerebellar pathology. An electroencephalogram was done in view of her recurrent seizures, which was normal. Initial laboratory work-up was normal. The patient then underwent magnetic resonance imaging (MRI) brain, acquired with a 1.5-T unit (Siemens, Erlangen, Germany). MRI brain revealed hemihypertrophy of left cerebellar hemisphere with disorganized architecture, fissural malorientation with individual folia running vertically rather than horizontally with disorganized foliation, abnormal arborization of white matter predominantly involving mid and dorsal surface of left cerebellar hemisphere and a few suspicious areas of abnormal T2-hyperintense signal in subcortical white matter. Right cerebellar hemisphere and cerebellar vermis were normal. Corpus callosum was normal. Cerebral parenchyma was normal in signal intensity pattern with normal gray-white matter differentiation. Ventricular system was normal (Figures 1 and 2). Cerebellar malformations are uncommon and are usually associated with Dandy-Walker continuum, Joubert syndrome, rhombencephalosynapsis, lissencephaly, Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, muscle-eye-brain disease, congenital cytomegalovirus infection to name a few.1,2 Isolated unilateral cerebellar hemispheric dysplasia is exceedingly rare with only a few cases previously described in English literature. Cerebellar malformations are less adequately understood entity partly because of the complex cerebellar embryology and limited histologic studies of these disorders. Genes expressed in migration and maintenance of the Purkinje cells and/or in the generation and migration of granular cells when mutated will disrupt cerebellar migration and foliation and thus cause cerebellar malformation.3-5 Cerebellum is known to be a centre for motor learning, coordination, and higher cognitive functions. Clinical presentation of cerebellar malformations is highly variable and depends on the degree of cerebellar involvement, presence of associated cerebral involvement and the underlying disorders such as muscular dystrophy if any. Patel and Barkovich suggested an imaging-based classification of cerebellar malformations and classified the malformations broadly into two types, malformations with cerebellar hypoplasia and the ones with cerebellar dysplasia. Each of these was further classified into focal and diffuse.1 Demaerel gave a classification of abnormalities of cerebellar foliation and fissuration.2 Our index case with disorganized architecture, fissural malorientation and disorganized foliation of left cerebellar hemisphere associated with normal cerebellar vermis, corpus callosum, and absence of cerebral malformation falls into Type 2 category as per the classification by Demaerel.2 Treatment depends upon the severity of symptoms and the underlying disorder in case of syndromic malformations. Generally, treatment is symptomatic and supportive. Understanding of the basics of cerebellar embryology, knowledge of the imaging features, and clinical presentation aids in the precise diagnosis of this disorder and its optimal management.


Assuntos
Doenças Cerebelares/diagnóstico por imagem , Cerebelo/anormalidades , Malformações do Sistema Nervoso/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Criança , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética
17.
Int J Dev Neurosci ; 78: 92-97, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31336146

RESUMO

BACKGROUND: Despite implementation of a controlled diet, children with classical galactosemia (CG) may develop a variety of developmental and cognitive problems. In this study, we examined the early developmental status of, as well as the neurological and neuroradiological findings for, children with CG. METHODS: We retrospectively evaluated 46 galactosemia patients who were followed between 2003 and 2017. We included those who exhibited CG and p.gln188arg homozygous mutation without concomitant disease and who had undergone detailed neurological examination, brain magnetic resonance imaging (MRI), and Denver II developmental testing. RESULTS: The mean ages at the time of the most recent neurological examination and Denver II testing were 48.5 ±â€¯28.5 months and 34.4 ±â€¯18.2 months, respectively. Developmental delay was defined as developmental age ≥ 20% lower than chronological age. The results were normal in 25 patients and delayed ≥ 20% in least in one domain, primarily in language development, in 21 patients. Brain MRI was abnormal in 22 patients. CONCLUSIONS: This analysis of the youngest children with the same genetic mutation reported thus far showed that, despite treatment, developmental delays and abnormalities on brain MRI may begin at an early age.


Assuntos
Encéfalo/diagnóstico por imagem , Deficiências do Desenvolvimento/etiologia , Galactosemias/complicações , Mutação , Convulsões/etiologia , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Feminino , Galactosemias/diagnóstico por imagem , Galactosemias/genética , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Exame Neurológico , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/genética
19.
BMC Med Genet ; 20(1): 88, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117962

RESUMO

BACKGROUND: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessively-inherited defect of γ-aminobutyric acid (GABA) metabolism. The absence of SSADH, which is encoded by aldehyde dehydrogenase family 5 member A1 (ALDH5A1) gene, leads to the accumulation of GABA and γ-hydroxybutyric acid (GHB). Few cases with SSADH deficiency were reported in China. CASE PRESENTATION: In this study, four Chinese patients were diagnosed with SSADH deficiency in Tianjin Children's Hospital. We conducted a multidimensional analysis with magnetic resonance imaging (MRI) of the head, semi quantitative detection of urine organic acid using gas chromatography-mass spectrometry, and analysis of ALDH5A1 gene mutations. Two of the patients were admitted to the hospital due to convulsions, and all patients were associated with developmental delay. Cerebral MRI showed symmetrical hyperintense signal of bilateral globus pallidus and basal ganglia in patient 1; hyperintensity of bilateral frontal-parietal lobe, widened ventricle and sulci in patient 2; and widened ventricle and sulci in patient 4. Electroencephalogram (EEG) revealed the background activity of epilepsy in patient 1 and the disappearance of sleep spindle in patient 2. Urine organic acid analysis revealed elevated GHB in all the patients. Mutational analysis, which was performed by sequencing the 10 exons and flanking the intronic regions of ALDH5A1 gene for all the patients, revealed mutations at five sites. Two cases had homozygous mutations with c.1529C > T and c.800 T > G respectively, whereas the remaining two had different compound heterozygous mutations including c.527G > A/c.691G > A and c.1344-2delA/c.1529C > T. Although these four mutations have been described previously, the homozygous mutation of c.800 T > G in ALDH5A1 gene is a novel discovery. CONCLUSION: SSADH deficiency is diagnosed based on the elevated GHB and 4, 5DHHA by urinary organic acid analysis. We describe a novel mutation p.V267G (c.800 T > G) located in the NAD binding domain, which is possibly crucial for this disease's severity. Our study expands the mutation spectrum of ALDH5A1 and highlights the importance of molecular genetic evaluation in patients with SSADH deficiency.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Análise Mutacional de DNA/métodos , Deficiências do Desenvolvimento/genética , Mutação , Succinato-Semialdeído Desidrogenase/deficiência , Succinato-Semialdeído Desidrogenase/genética , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico por imagem , Erros Inatos do Metabolismo dos Aminoácidos/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Pré-Escolar , China , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/etnologia , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética/métodos , Masculino , Succinato-Semialdeído Desidrogenase/metabolismo
20.
Seizure ; 69: 228-234, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112829

RESUMO

PURPOSE: To summarize the clinical features and neuroimaging changes of epilepsy associated with TBC1D24 mutations. METHODS: Genetic testing was conducted in all epilepsy patients without acquired risk factors for epilepsy. Epilepsy patients identified with TBC1D24 compound heterozygous mutations by next-generation sequencing (NGS) epilepsy panel or whole exome sequencing (WES) were enrolled. The enrolled patients were followed up to summarize the clinical features. RESULTS: Nineteen patients were identified with TBC1D24 compound heterozygous mutations. Nine patients carried the same pathogenic variant c.241_252del. The seizure onset age ranged from 1 day to 8 months of age (median age 75 days). The most prominent features were multifocal myoclonus and epilepsia partialis continua (EPC). Myoclonus could be triggered by fever or infection in 15 patients, and could be terminated by sleep or sedation drugs. Psychomotor developmental delay was presented in 11 patients. Six patients exhibited hearing loss. Brain MRIs were abnormal in eight patients. Twelve patients were diagnosed with epilepsy syndromes including one patient who was diagnosed with Dravet syndrome. Two patients died due to status epilepticus at 4 months and 19 months of age, respectively. CONCLUSION: TBC1D24 mutation related epilepsy was drug-resistant. Multifocal myoclonus, EPC, and fever-induced seizures were common clinical features. Most patients presented psychomotor developmental delay. The neuroimaging abnormality and hearing loss could exacerbate during follow-up.


Assuntos
Epilepsia/genética , Proteínas Ativadoras de GTPase/genética , Mutação , Mioclonia/genética , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/terapia , Epilepsia Parcial Contínua/diagnóstico por imagem , Epilepsia Parcial Contínua/genética , Epilepsia Parcial Contínua/fisiopatologia , Epilepsia Parcial Contínua/terapia , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Epilepsia/terapia , Feminino , Seguimentos , Predisposição Genética para Doença , Perda Auditiva/diagnóstico por imagem , Perda Auditiva/genética , Perda Auditiva/fisiopatologia , Perda Auditiva/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Mioclonia/diagnóstico por imagem , Mioclonia/fisiopatologia , Mioclonia/terapia , Convulsões Febris/diagnóstico por imagem , Convulsões Febris/genética , Convulsões Febris/fisiopatologia , Convulsões Febris/terapia
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