Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies.

Leukodystrophies are a broad class of genetic disorders that result in disruption or destruction of central myelination. Although the mechanisms underlying these disorders are heterogeneous, there are many common symptoms that affect patients irrespective of the genetic diagnosis. The comfort and quality of life of these children is a primary goal that can complement efforts directed at curative therapies. Contained within this report is a systems-based approach to management of complications that result from leukodystrophies. We discuss the initial evaluation, identification of common medical issues, and management options to establish a comprehensive, standardized care approach. We will also address clinical topics relevant to select leukodystrophies, such as gallbladder pathology and adrenal insufficiency. The recommendations within this review rely on existing studies and consensus opinions and underscore the need for future research on evidence-based outcomes to better treat the manifestations of this unique set of genetic disorders.

Early occurrence of cerebral white matter abnormality detected in a neonate with salt-wasting congenital adrenal hyperplasia.

The development of white matter signal abnormalities on magnetic resonance brain imaging (MRI) in children and young adults with congenital adrenal hyperplasia has been well documented. Existing theories regarding the development of these findings include effects of electrolyte imbalances, effects of disease-related hormone abnormalities, and non-physiologic long-term administration of corticosteroids. Many of the patients previously described were normal neurologically. We describe the case of white matter signal abnormalities in a neonate with salt-wasting congenital adrenal hyperplasia who presented with seizures during the first week of life, possibly due to a transient blood calcium disturbance. This case suggests that white matter changes are not simply the result of chronic insults and that they may not always be subclinical.

Diffusion-weighted imaging in fetuses with severe congenital heart defects.

Fetal diffusion MR imaging was performed in 3 fetuses with CHD. ADC values in the periatrial WM, thalamus, and basal ganglia were compared with those in a control population of fetuses. Diffusivity in the periatrial WM and thalamus was higher for the fetuses with CHD compared with controls. These observations support the finding of abnormal in utero brain development in fetuses with CHD.

Diagnóstico retrospectivo de infección congénita por citomegalovirus en un caso clínico infantil / Retrospective diagnosis of congenital infection by cytomegalovirus int he case of one infant

Introduction. 10-15% of asymptomatic congenital infections by cytomegalovirus (CMV) in the neonatal period develop persistent problems with varying degrees of severity, fundamentally involving neurological disorders, neurosensory hypoacusis and hypovision, which appear from the age of 6-9 months onwards, when a diagnosis is no longer possible. The PCR (polymerase chain reaction) technique can detect DNA of CMV in blood samples on filter paper used for screening hypothyroidism and metabolic pathologies that were kept from the neonatal period. Case report. A child aged 3 years and 8 months with delayed intrauterine growth, autism, mental retardation, microcephalus and neurosensory hypoacusis; periventricular calcifications, leukoencephalopathy and bilateral malformation of the temporal lobe; and a diagnosis of congenital CMV confirmed by detection of DNA by PCR in the blood sample on filter paper saved from the neonatal period. Conclusions. The retrospective study of congenital infection by CMV should be considered when faced with severity and varying association of delayed intrauterine growth, microcephalus, neurosensory hypoacusis, chorioretinitis, mental retardation, autism or other behavioural disorders, intracranial calcifications, encephaloclastic alterations, leukoencephalopathy, cortical dysplasia and malformations of the temporal lobe and the hippocampus. Since the filter papers from neonatal screening are not kept for ever, perhaps the idea of doing so ought to be considered, given the possibilities they offer for retrospective studies (AU)

Introducción. Un 10-15% de las infecciones congénitas por citomegalovirus (CMV) asintomáticas en el período neonatal desarrollan problemas persistentes de gravedad variable, fundamentalmente afectación neurológica, hipoacusia neurosensorial e hipovisión, que se manifiestan a partir de los 6-9 meses, cuando ya no es posible efectuar el diagnóstico. La técnica de la PCR (del inglés, polymerase chain reaction) puede detectar el ADN del CMV en las muestras de sangre del papel de filtro que se emplean para el cribaje de hipotiroidismo y metabolopatías, guardadas desde el período neonatal. Caso clínico. Se trata de un niño de 3 años y 8 meses de edad con retraso de crecimiento intrauterino, autismo, retraso mental, microcefalia e hipoacusia neurosensorial, con calcificaciones periventriculares, leucoencefalopatía y malformación bilateral del lóbulo temporal, con confirmación diagnóstica de CMV congénito por detección del ADN mediante PCR en la sangre del papel de filtro guardado desde el período neonatal. Conclusiones. El estudio retrospectivo de infección congénita por CMV debería plantearse ante la presencia de gravedad y asociación variables de retraso de crecimiento intrauterino, microcefalia, hipoacusia neurosensorial, coriorretinitis, retraso mental, autismo u otros problemas de conducta, calcificaciones intracraneales, alteraciones encefaloclásticas, leucoencefalopatía, displasia cortical y malformaciones del lóbulo temporal y el hipocampo. Dado que los papeles de filtro de cribaje neonatal no se guardan indefinidamente, se plantea la posibilidad de hacerlo, dadas las posibilidades de estudios retrospectivos que ofrecen (AU)