RESUMEN
Children with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1+/-). Children with NF1 demonstrated abnormal organization of cortical association networks and altered posterior-anterior functional connectivity in the default network. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered. NF1 children demonstrated reduced functional connectivity between striatum and the frontoparietal network and increased striatal functional connectivity with the limbic network. Awake passive mouse functional connectivity MRI in Nf1+/- mice similarly revealed reduced posterior-anterior connectivity along the cingulate cortex as well as disrupted corticostriatal connectivity. The striatum of Nf1+/- mice showed increased functional connectivity to somatomotor and frontal cortices and decreased functional connectivity to the auditory cortex. Collectively, these results demonstrate similar alterations across species, suggesting that NF1 pathogenesis is linked to striatal dysfunction and disrupted corticocortical connectivity in the default network.
Asunto(s)
Trastorno Autístico/etiología , Encéfalo/patología , Vías Nerviosas/patología , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/patología , Adolescente , Animales , Encéfalo/diagnóstico por imagen , Niño , Modelos Animales de Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Ratones , Vías Nerviosas/diagnóstico por imagen , Neurofibromatosis 1/diagnóstico por imagenRESUMEN
BACKGROUND: Arrest of fetal brain development and the fetal brain disruption sequence describe a severe phenotype involving microcephaly, occipital bone prominence, and scalp rugae. Congenital disorders of glycosylation are a heterogeneous group of inherited disorders involved in glycoprotein and glycolipid biosynthesis, which can cause microcephaly and severe neurodevelopmental disability. METHODS: We report an example of fetal microcephaly diagnosed at 36 weeks' gestation with a history of normal fetal biometry at 20 weeks' gestation. Postnatal genetic testing was performed. RESULTS: Fetal magnetic resonance imaging at 36 weeks' gestational age showed severe cortical thinning with a simplified gyral pattern for gestational age, ventriculomegaly, and agenesis of the corpus callosum. The fetal skull had a posterior shelf at the level of the lambdoid suture, characteristic of fetal brain disruption sequence. Postnatal brain magnetic resonance imaging found no brain growth during the interval from the fetal to postnatal study. The infant was found to have biallelic pathologic mutations in ALG11. CONCLUSIONS: Arrest of fetal brain development, with image findings consistent with fetal brain disruption sequence, is a previously unreported phenotype of congenital microcephaly in ALG11-congenital disorder of glycosylation. ALG11-congenital disorder of glycosylation should be considered in the differential diagnosis of this rare form of congenital microcephaly.
Asunto(s)
Encéfalo/diagnóstico por imagen , Trastornos Congénitos de Glicosilación/diagnóstico por imagen , Desarrollo Fetal , Manosiltransferasas/genética , Microcefalia/diagnóstico por imagen , Encéfalo/patología , Trastornos Congénitos de Glicosilación/genética , Trastornos Congénitos de Glicosilación/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Microcefalia/genética , Microcefalia/patologíaRESUMEN
The role of MRI in the evaluation of fetal abnormalities is still under evaluation. We describe a case of an intracranial mass that was initially identified by prenatal ultrasound and was further evaluated by MRI. Ultimately, the findings were most consistent with hematoma secondary to an underlying dural malformation with spontaneous involution. The advantages of fetal MRI in the assessment and management of this abnormality will be discussed.