ABSTRACT
Type 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3-5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI). Moreover, in all the cases showing an inherited candidate variant, brain MRI was performed in both parents and not only in the carrier one to investigate whether the defect segregated with the variant. More than half of the variants were Missense and belonged to the same chromatin-remodeling genes whose protein truncation variants are associated with severe neurodevelopmental syndromes. In the remaining cases, variants have been detected in genes with a role in cranial bone sutures, microcephaly, neural tube defects, and RASopathy. This study shows that the frequency of C1M is widely underestimated, in fact many of the variants, in particular those in the chromatin-remodeling genes, were inherited from a parent with C1M, either asymptomatic or with mild symptoms. In addition, C1M is a Mendelian trait, in most cases inherited as dominant. Finally, we demonstrate that modifications of the genes that regulate chromatin architecture can cause localized anatomical alterations, with symptoms of varying degrees.
Subject(s)
Arnold-Chiari Malformation/genetics , Chromatin Assembly and Disassembly/genetics , Exome Sequencing , Mutation, Missense , Adolescent , Arnold-Chiari Malformation/diagnostic imaging , Arnold-Chiari Malformation/epidemiology , Child , Child, Preschool , Female , Humans , Infant , MAP Kinase Signaling System/genetics , Magnetic Resonance Imaging , Male , Microcephaly/genetics , Young AdultABSTRACT
The aim of this paper is to provide indications for performing magnetic resonance enterography (MRE) in Crohn's disease (CD), the essential technical elements of MRE techniques and typical findings in patients with CD. Patients suffering from CD frequently require cross-sectional imaging. By performing MRE, it is possible to obtain results comparable to those obtained with endoscopy in terms of identifying and assessing disease activity and better than other cross-sectional imaging techniques, such as CT, in the evaluation of the fibrosis and complications of disease. The MR imaging of diffusion MR is a technique which enables medical staff to add important additional information and which may replace the use of intravenous contrast agents in the near future. Magnetic resonance enterography is an accurate tool for assessing bowel disease and the various complications associated with CD. The lack of exposure to non-ionizing radiation is an important advantage of this imaging technique, especially in the case of pediatric patients. Familiarity with common and pathognomonic imaging features of CD is essential for every clinician involved in the treatment of inflammatory bowel disease and the care of patients.
Subject(s)
Crohn Disease/diagnosis , Magnetic Resonance Imaging , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging/methods , Humans , Magnetic Resonance Imaging/methods , Predictive Value of Tests , Risk Assessment , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
PURPOSE: To evaluate the image quality and the diagnostic efficacy by single-phase whole-body 64-slice multidetector CT (MDCT) for pediatric oncology. PATIENTS AND METHODS: Chest-abdomen-pelvis CT examinations with single-phase split-bolus technique were evaluated for T: detection and delineation of primary tumor (assessment of the extent of the lesion to neighboring tissues), N: regional lymph nodes and M: distant metastasis. Quality scores (5-point scale) were assessed by two radiologists on parenchymal and vascular enhancement. RESULTS: Accurate TNM staging in term of detection and delineation of primary tumor, regional lymph nodes and distant metastasis was obtained in all cases. On the image quality and severity artifact, the Kappa value for the interobserver agreement measure obtained from the analysis was 0.754, (p<0.001), characterizing a very good agreement between observers. CONCLUSION: Single-pass total body CT split-bolus technique reached the highest overall image quality and an accurate TNM staging in pediatric patients with cancer.