Early identification of a 12-bp tandem duplication in TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK): Clinical characterization and response to bisphosphonate therapy.

INTRODUCTION: Ultra-rare mendelian osteolytic disorders caused by different length in-frame activating duplications within exon 1 of TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK) comprise familial expansile osteolysis (FEO), expansile skeletal hyperphosphatasia (ESH), early-onset familial Paget's disease of bone (PDB2), juvenile Paget's disease 2 (JPD2), and panostotic expansile bone disease (PEBD). FEO typically presents with childhood-onset deafness followed by resorption of permanent dentition, and then appendicular bone pain, fractures, and deformities from progressive focal expansile osteolytic lesions emerging from a background of generalized high bone turnover. An 18-bp duplication in TNFRSF11A has been reported in all kindreds with FEO, whereas a 12-bp duplication was found in the young man with PEBD complicated by a massive jaw tumor. We report the clinical course and successful treatment with bisphosphonates of a girl with the 12-bp duplication yet a skeletal phenotype seemingly milder than PEBD. CASE PRESENTATION AND DISCUSSION: This 10-year-old girl presented for dental and orthodontic treatment and was found to have progressive external tooth root resorption. Speech delay was identified at age 18 months, and audiological evaluation showed both conductive and sensorineural hearing loss subsequently treated with a cochlear implant at age 3 years. Biochemical studies indicated increased bone turnover with elevated urinary N-telopeptide levels and serum alkaline phosphatase in the upper normal range. Low lumbar spine bone mineral density (BMD) was revealed by dual-energy X-ray absorptiometry, but whole-body Technetium-99 m bone scintigraphy was normal. Genetic testing identified the identical de novo 12-bp duplication within exon 1 of TNFRSF11A harbored by the young man with PEBD and massive jaw tumor. Bisphosphonate treatment, initiated with one dose of intravenous zoledronic acid that caused prolonged hypocalcemia, then comprised weekly oral alendronate that decreased bone turnover markers and normalized her BMD. CONCLUSION: Constitutive activation of RANK signaling should be considered a possible cause in any young person with rapid bone turnover, particularly in the context of early-onset deafness and/or root resorption of permanent teeth. Early diagnosis and anti-resorptive treatment, given judiciously to avoid sudden and prolonged hypocalcemia, may prevent further skeletal disease.

Late Diagnosis of Congenital Toxoplasmosis with Macrocephaly in Dizygotic Twins after Incidental Detection of Leukocoria: A Case Report.

Untreated congenital toxoplasmosis remains an important cause of neurologic and ocular disease worldwide. However, congenitally infected infants may not have signs and symptoms their physicians recognize, leading to delayed diagnosis and missed opportunities for treatment. We describe a pair of twins diagnosed with congenital toxoplasmosis at 11 months of age following incidental detection of leukocoria in one twin.

Job-Readiness After Pediatric Neuroradiology Training: Defining Trainee Needs.

RATIONALE AND OBJECTIVES: To describe and analyze the pediatric neuroradiology implicit curriculum for general-pediatric and neuro-pediatric radiology fellowship training in order to define specific trainee needs and inform an explicit pediatric neuroradiology curriculum. MATERIALS AND METHODS: A focus group of pediatric radiologists, pediatric neuroradiologists and fellows was conducted to create a needs assessment questionnaire that focused on training experience, current job, and a list of essential competency items. The questionnaire was distributed to 175 members of the Society for Pediatric Radiology. Data were derived from categorical and continuous survey variables. Using an inductive approach, we analyzed and systematically inspected the data to derive themes regarding trainee needs and how they might inform an explicit curriculum. RESULTS: Fifty-seven pediatric radiologists (response rate of 33%) responded to the survey. Sixty-three percent of respondents were fellowship trained in general pediatric radiology, 21% in pediatric neuroradiology, and 16% in both. In their current jobs, 75% of respondents were responsible for interpreting some pediatric neuroradiology. 50% or greater reported limited or no fellowship instruction in five areas of imaging interpretation: fetal neuroimaging; ear and/or nose and/or throat imaging; head and neck imaging; neuroembryology; neuro-spectroscopy and four areas of technical skills and/or image quality: reducing imaging time; choice of contrast agents; sedation; understanding clinical management pathways. CONCLUSION: Trainees endorse inadequate training in certain aspects of imaging interpretation and technical skills which are known to remain a significant and vital aspect of pediatric neuroradiology practice, revealing an opportunity to emphasize these aspects in an explicit curriculum and dedicate educational resources towards this cause.

Imaging of Pediatric Hearing Loss.

Temporal bone high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging are valuable tools in the evaluation of pediatric hearing loss. Computed tomography is important in the evaluation of pediatric conductive hearing loss and is the imaging modality of choice for evaluation of osseous abnormalities. MR imaging is the modality of choice for evaluation of sensorineural hearing loss. A broad spectrum of imaging findings can be seen with hearing loss in children. HRCT and MR imaging provide complementary information and are often used in conjunction in the preoperative evaluation of pediatric candidates for cochlear implantation.

Predictors of pediatric blunt cerebrovascular injury.

BACKGROUND/PURPOSE: Blunt cerebrovascular injury (BCVI) is clinically challenging because these injuries are hard to detect and can have serious neurological consequences, and optimal screening criteria have not been established for children. This study aims to determine risk factors for BCVI in pediatric patients and to evaluate screening practices in a single institutional series. METHODS: A retrospective review of all pediatric blunt trauma patients evaluated over a 10-year period was performed. Demographic, clinical, and radiographic data were reviewed, including the presence of adult risk factors for BCVI. Logistic regression analyses were performed with statistical significance established at p<0.05. RESULTS: Of the 11,596 patients evaluated during the study period, 1018 (8.8%) had at least one adult risk factor for BCVI, but only 62 (6.1% of those with risk factors) underwent angiographic evaluation. Overall, 11 BCVIs were observed, resulting in an incidence of 0.095%. All 11 patients with BCVI had at least one risk factor. Multivariate logistic regression analysis identified cervical spine fracture (OR 36.88 [8.36, 169.95]), GCS score ≤ 8 (OR 16.42 [2.16, 102.33]), male gender (OR 10.52 [1.33, 363.30]), Le Fort II or III facial fracture (OR 63.71 [2.16, 1124.68]), and ISS (unit OR 1.10 [1.04, 1.17]) as independent risk factors for BCVI. CONCLUSION: Adult screening criteria for BCVI appear appropriate for pediatric patients, but most at-risk children are not being screened. LEVEL OF EVIDENCE: Level III (retrospective case-control study).

Brain Tumors in the Neonate.

Brain tumors can develop in the prenatal and neonatal time periods. Neuroimaging studies are crucial for the early detection of prenatal and neonatal brain tumors. Imaging allows for characterization of morphology, as well as the detection of hydrocephalus, local invasion, and distant spread. The imaging features of the more common neonatal brain tumors, including teratomas, choroid plexus tumors, ATRTs, and neoplasm mimics are described.

The Implications of Brain MRI in Autism Spectrum Disorder.

Our objective was to describe the types of providers who refer children with autism spectrum disorder (ASD) for brain magnetic resonance imaging (MRI), the referral reason, and MRI results. The most common referral reasons were autism spectrum disorder with seizures (33.7%), autism spectrum disorder alone (26.3%), and autism spectrum disorder with abnormal neurologic examination or preexisting finding (24%). Neurology (62.5%), general pediatric (22.3%), and developmental/behavioral practitioners (8.9%) referred the most patients. The prevalence of definite pathology was highest in children referred for autism spectrum disorder with abnormal neurologic examination/preexisting finding (26.2%, 95% CI: 16.8%-36%), headaches (25.7%, 95% CI: 11.2%-40.2%), or seizures (22%, 95% CI: 14.6%-29.5%), and was lowest in children referred for autism spectrum disorder alone (6.5%, 95% CI: 1.5%-11.6%). We concluded that there is a low prevalence of definite pathology in children with autism spectrum disorder undergoing brain MRI. In children with abnormal neurologic examination or preexisting finding, seizures, or headaches, one may consider performing brain MRI given the higher prevalence of pathology.

Magnetic resonance imaging of the pediatric neck: an overview.

Evaluation of neck lesions in the pediatric population can be a diagnostic challenge, for which magnetic resonance (MR) imaging is extremely valuable. This article provides an overview of the value and utility of MR imaging in the evaluation of pediatric neck lesions, addressing what the referring clinician requires from the radiologist. Concise descriptions and illustrations of MR imaging findings of commonly encountered pathologic entities in the pediatric neck, including abnormalities of the branchial apparatus, thyroglossal duct anomalies, and neoplastic processes, are given. An approach to establishing a differential diagnosis is provided, and critical points of information are summarized.

Fetal MRI: head and neck.

Abnormalities of the fetal head and neck may be seen in isolation or in association with central nervous system abnormalities, chromosomal abnormalities, and syndromes. Magnetic resonance imaging (MRI) plays an important role in detecting associated abnormalities of the brain as well as in evaluating for airway obstruction that may impact prenatal management and delivery planning. This article provides an overview of the common indications for MRI of the fetal head and neck, including abnormalities of the fetal skull and face, masses of the face and neck, and fetal goiter.