RESUMO
Cerebellofaciodental syndrome is characterized by facial dysmorphisms, intellectual disability, cerebellar hypoplasia, and dental anomalies. It is an autosomal-recessive condition described in 2015 caused by pathogenic variants in BRF1. Here, we report a Brazilian patient who faced a diagnostic challenge beginning at 11 months of age. Fortunately, whole-exome sequencing (WES) was performed, detecting the BRF1 variants NM_001519.3:c.1649delG:p.(Gly550Alafs*36) and c.421C>T:p.(Arg141Cys) in compound heterozygosity, thus finally achieving a diagnosis of cerebellofaciodental syndrome. The patient is currently 25 years old and is the oldest patient yet reported. The clinical report and a review of published cases are presented. Atlanto-occipital fusion, a reduced foramen magnum and basilar invagination leading to compression of the medulla-spinal cord transition are skeletal findings not reported in previous cases. The description of syndromes with dental findings shows that such anomalies can be an important clue to relevant differential diagnoses. The cooperation of groups from different international centers made possible the resolution of this and other cases and is one of the strategies to bring medical advances to developing countries, where many patients with rare diseases are difficult to diagnose definitively.
Assuntos
Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Anormalidades Craniofaciais/genética , Deficiência Intelectual/genética , Atrofia Muscular/genética , Malformações do Sistema Nervoso/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Anormalidades Dentárias/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/fisiopatologia , Adulto , Brasil/epidemiologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/fisiopatologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/fisiopatologia , Masculino , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/fisiopatologia , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/fisiopatologia , Anormalidades Dentárias/diagnóstico por imagem , Anormalidades Dentárias/fisiopatologia , Sequenciamento do ExomaRESUMO
OBJECTIVE: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. STUDY DESIGN: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. RESULTS: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. CONCLUSIONS: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00614744.
Assuntos
Deficiências do Desenvolvimento/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Imageamento por Ressonância Magnética , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
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 , UltrassonografiaAssuntos
Hipopigmentação/diagnóstico por imagem , Pele/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/diagnóstico por imagem , Humanos , Hipopigmentação/complicações , Síndrome de Lennox-Gastaut/complicações , Síndrome de Lennox-Gastaut/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Síndromes Neurocutâneas/complicações , Síndromes Neurocutâneas/diagnóstico por imagemRESUMO
Congenital Zika virus infection has stimulated great international concern. A prospective case series of 87 infants with laboratory-confirmed congenital Zika syndrome (CZS) at the epicenter of the Brazilian Zika epidemic in Pernambuco state is presented. Mothers were interviewed for symptoms of possible Zika virus (ZIKV) infection during pregnancy, and fetal ultrasounds were obtained. Infant cerebrospinal fluid (CSF) samples were tested for ZIKV-specific antibodies, and sera were screened for other congenital infections. Neuroimaging and ophthalmologic evaluations were also performed. Sixty-six mothers (76%) reported symptoms of ZIKV infection during gestation. Fetal ultrasounds were available from 90% of the mothers, and all demonstrated brain structural abnormalities. All of the CSF samples tested positive for ZIKV immunoglobulin M. The majority of infants (89%) were term; the mean birth weight was 2577 ± 260 g, and the mean head circumference was 28.1 ± 1.8 cm. Severe microcephaly, defined as head circumference 3 SD below the mean for sex and gestational age, was found in 72 (82%) infants. All infants had an abnormal neurological exam, and 18 (20.7%) had arthrogryposis. The main abnormalities detected in computed tomography scans were calcifications (99%), followed by ventricular enlargement (94%), cortical hypogyration (81%), and less commonly, cerebellar hypoplasia (52%). Unilateral diaphragm paralysis was identified in 3 infants. Maternal young age, term infant, small for gestational age, and the presence of ophthalmologic abnormalities were significantly associated with a smaller head circumference Z score. Our findings, based on laboratory-confirmed ZIKV infection, add valuable evidence for the understanding of CZS.
Assuntos
Epidemias , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/congênito , Infecção por Zika virus/epidemiologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Artrogripose/epidemiologia , Artrogripose/virologia , Encéfalo/anormalidades , Encéfalo/virologia , Brasil/epidemiologia , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Cerebelo/virologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/virologia , Epidemias/estatística & dados numéricos , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/virologia , Idade Gestacional , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidiano , Lactente , Microcefalia/diagnóstico por imagem , Microcefalia/epidemiologia , Microcefalia/virologia , Mães , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/epidemiologia , Malformações do Sistema Nervoso/virologia , Neuroimagem , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Paralisia Respiratória/diagnóstico por imagem , Paralisia Respiratória/epidemiologia , Paralisia Respiratória/virologia , Ultrassonografia , Zika virus/imunologia , Zika virus/isolamento & purificação , Infecção por Zika virus/virologiaRESUMO
INTRODUCTION: MRI characterization of dysferlinopathy has been mostly limited to the lower limbs. We aimed to broaden the MRI description of dysferlinopathy and to correlate it with objective measures of motor dysfunction. METHODS: Sequential whole-body axial MRI was performed in 27 patients with genetically confirmed dysferlinopathy classified according to disease duration. Spearman correlations of fatty infiltration scores versus Motor Function Measure (MFM) were calculated. RESULTS: Significant fatty infiltration was symmetrically present in early stages mainly in the posterior compartments of legs and thighs, thigh adductors, pelvic girdle, and some paravertebral muscles and the subscapularis. Later, fatty infiltration involved leg and thigh anterior compartments, arms and forearms, paravertebral, and trunk muscles. MRI infiltration score correlated positively with disease duration and negatively with MFM scale. CONCLUSIONS: We expand MRI characterization of dysferlinopathy and provide evidence for use of MRI scoring combined with motor functional scales to assess the natural course of disease. Muscle Nerve, 2016 Muscle Nerve 54: 203-210, 2016.
Assuntos
Imageamento por Ressonância Magnética , Distrofia Muscular do Cíngulo dos Membros/diagnóstico por imagem , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Imagem Corporal Total , Adolescente , Criança , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Músculo Esquelético/diagnóstico por imagem , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto JovemRESUMO
OBJECTIVE: To report the accuracy of ultrasound scanning (US) in predicting neurodevelopmental and sensorineural outcome in patients with congenital cytomegalovirus (CMV) infection. STUDY DESIGN: Fifty-seven neonates with congenital CMV infection underwent brain US and were observed prospectively for motor skills, developmental quotient, and hearing function. RESULTS: Abnormal results on US were found in 12 of 57 neonates. US lesions were more frequent in newborns with clinical and laboratory signs of congenital CMV infection at birth (10/18) than in newborns who had no symptoms at birth (2/39; P < .001). At least 1 sequela developed in all neonates with symptoms who had abnormal US results, whereas none of the neonates with symptoms who had normal US results had long-term sequelae (P < .001). In the population without symptoms, sensorineural hearing loss developed in 3 of 37 (8.1%) neonates with normal US results, whereas severe sequelae developed in 1 of 2 neonates with abnormal US results. CONCLUSIONS: A good correlation was found between cerebral US abnormalities and the prediction of outcome in newborns who were congenitally infected with CMV and had symptoms at birth. US could be performed as the first neuroimaging study in these newborns. Data are insufficient to permit any suggestions for the population without symptoms.
Assuntos
Encefalopatias/diagnóstico por imagem , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico por imagem , Ultrassonografia Doppler , Peso ao Nascer , Encefalopatias/etiologia , Infecções por Citomegalovirus/complicações , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/virologia , Feminino , Idade Gestacional , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/virologia , Humanos , Incidência , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Razão de Chances , Valor Preditivo dos Testes , Probabilidade , Prognóstico , Estudos Prospectivos , Medição de Risco , Tomografia Computadorizada por Raios XRESUMO
The purpose of the present study was to ascertain whether artificial skull deformation, carried out during infancy, has an effect on the pneumatization of the frontal and maxillary sinuses and on the osseous structure of the frontal bone. Thus, two normal and 12 artificially deformed adult human skulls (12 males, two females) from the collection of pre-Columbian Peruvian skeletons and mummies in the Institute of Anthropology and Human Genetics (University of Munich) were investigated by computed tomography. These skulls had been excavated from four sites on the Peruvian coast: Las Trancas, Cahuachi. Pacatnamu, and Estaqueria. The volumes of the maxillary sinuses varied from 5.18 mL to 17.19 mL. Those of the frontal sinuses varied from zero to 6.21 mL. The artificial deformation of the skull, which occurred during infancy, had no influence on the size of the maxillary and frontal sinuses. There was also no difference in the average bone thickness of the os frontale; however, artificial deformation in infancy had an influence on the bone structure, resulting in a tremendous rarefication of the diploe of the frontal bones. Based on these findings we conclude that the various types of skull deformation instituted in infancy seem to exert no inhibitory effect on the pneumatization of either the frontal or maxillary sinuses.