De novo variants in SP9 cause a novel form of interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity.

PURPOSE: Interneuronopathies are a group of neurodevelopmental disorders characterized by deficient migration and differentiation of gamma-aminobutyric acidergic interneurons resulting in a broad clinical spectrum, including autism spectrum disorders, early-onset epileptic encephalopathy, intellectual disability, and schizophrenic disorders. SP9 is a transcription factor belonging to the Krüppel-like factor and specificity protein family, the members of which harbor highly conserved DNA-binding domains. SP9 plays a central role in interneuron development and tangential migration, but it has not yet been implicated in a human neurodevelopmental disorder. METHODS: Cases with SP9 variants were collected through international data-sharing networks. To address the specific impact of SP9 variants, in silico and in vitro assays were carried out. RESULTS: De novo heterozygous variants in SP9 cause a novel form of interneuronopathy. SP9 missense variants affecting the glutamate 378 amino acid result in severe epileptic encephalopathy because of hypomorphic and neomorphic DNA-binding effects, whereas SP9 loss-of-function variants result in a milder phenotype with epilepsy, developmental delay, and autism spectrum disorder. CONCLUSION: De novo heterozygous SP9 variants are responsible for a neurodevelopmental disease. Interestingly, variants located in conserved DNA-binding domains of KLF/SP family transcription factors may lead to neomorphic DNA-binding functions resulting in a combination of loss- and gain-of-function effects.

Can we improve accuracy and reliability of MRI interpretation in children with optic pathway glioma? Proposal for a reproducible imaging classification.

INTRODUCTION: Magnetic resonance (MR) images from children with optic pathway glioma (OPG) are complex. We initiated this study to evaluate the accuracy of MR imaging (MRI) interpretation and to propose a simple and reproducible imaging classification for MRI. METHODS: We randomly selected 140 MRIs from among 510 MRIs performed on 104 children diagnosed with OPG in France from 1990 to 2004. These images were reviewed independently by three radiologists (F.T., 15 years of experience in neuroradiology; D.L., 25 years of experience in pediatric radiology; and J.L., 3 years of experience in radiology) using a classification derived from the Dodge and modified Dodge classifications. Intra- and interobserver reliabilities were assessed using the Bland-Altman method and the kappa coefficient. These reviews allowed the definition of reliable criteria for MRI interpretation. RESULTS: The reviews showed intraobserver variability and large discrepancies among the three radiologists (kappa coefficient varying from 0.11 to 1). These variabilities were too large for the interpretation to be considered reproducible over time or among observers. A consensual analysis, taking into account all observed variabilities, allowed the development of a definitive interpretation protocol. Using this revised protocol, we observed consistent intra- and interobserver results (kappa coefficient varying from 0.56 to 1). The mean interobserver difference for the solid portion of the tumor with contrast enhancement was 0.8 cm(3) (limits of agreement = -16 to 17). CONCLUSION: We propose simple and precise rules for improving the accuracy and reliability of MRI interpretation for children with OPG. Further studies will be necessary to investigate the possible prognostic value of this approach.

Pediatric cervical spine in emergency: radiographic features of normal anatomy, variants and pitfalls.

Injuries of the cervical spine are uncommon in children. The distribution of injuries, when they do occur, differs according to age. Young children aged less than 8 years usually have upper cervical injuries because of the anatomic and biomechanical properties of their immature spine, whereas older children, whose biomechanics more closely resemble those of adults, are prone to lower cervical injuries. In all cases, the pediatric cervical spine has distinct radiographic features, making the emergency radiological analysis of it difficult. Such features as hypermobility between C2 and C3, pseudospread of the atlas on the axis, pseudosubluxation, the absence of lordosis, anterior wedging of vertebral bodies, pseudowidening of prevertebral soft tissue and incomplete ossification of synchondrosis can be mistaken for traumatic injuries. The interpretation of a plain radiograph of the pediatric cervical spine following trauma must take into account the age of the child, the location of the injury and the mechanism of trauma. Comprehensive knowledge of the specific anatomy and biomechanics of the childhood spine is essential for the diagnosis of suspected cervical spine injury. With it, the physician can, on one hand, differentiate normal physes or synchondroses from pathological fractures or ligamentous disruptions and, on the other, identify any possible congenital anomalies that may also be mistaken for injury. Thus, in the present work, we discuss normal radiological features of the pediatric cervical spine, variants that may be encountered and pitfalls that must be avoided when interpreting plain radiographs taken in an emergency setting following trauma.

The correlation between prenatal ultrasound and MRI in isolated periventricular pseudocysts: Analysis of 10 years' experience at the University Hospital of Angers.

BACKGROUND: Periventricular cysts are one of the most extensively documented antenatal brain lesions found through fetal ultrasound at the University Hospital of Angers. The main purpose of our study was to determine the contribution of fetal magnetic resonance imaging (MRI) and postnatal transfontanellar ultrasound (TFU) in the assessment of isolated periventricular cysts found on antenatal ultrasound at the University Hospital of Angers. METHODS: This retrospective, descriptive study was carried out over a 10-year period. Overall, 82 cases were included, divided into two groups according to the type of cysts found on the ultrasound: 13 cases of subependymal pseudocysts (SEPC) and 69 cases of frontal horn cysts (FHC). In all, 43 children underwent a postnatal TFU: seven in the SEPC group and 36 in the FHC group. RESULTS: Our study found excellent agreement between antenatal ultrasound and fetal MRI in the FHC group concerning classification of the cysts (approval rate [TA]: 98.60%; kappa coefficient [κ]: 0.85), their location (TA: 98.80%; κ: 0.91), their number (TA: 78.20%; κ: 0.73), and the detection of FHC (TA: 81.10%; κ: 0.74), as well as a good agreement concerning the detection of SEPC and temporal horn cysts (THC; TA: 99.40% and 95.60%, respectively). Fetal MRI proved to be better in the SEPC group for cyst classification (TA: 66.70%; κ: 0.33), their location (TA: 60%; κ: 0.41), and their number (TA: 53, 30%; κ: 0.45) and the detection of SEPC (TA: 23.10%; κ: 0.14). In both groups, postnatal TFU did not provide additional information compared to MRI. CONCLUSION: The finding of periventricular cysts in antenatal ultrasound should lead to a reference ultrasound, a key procedure for distinguishing between SEPC and FHC. In our study, no additional benefit from MRI and TFU was established for the evaluation of FHC. These findings should be considered as normal variants, thus limiting pre- and postnatal investigations. The visualization of SEPC, THC, or a parenchymal abnormality on the reference ultrasound should lead to an additional MRI being performed and a personalized follow-up of the child.

Occurrence of aortic aneurysms in 5 cases of Wiskott-Aldrich syndrome.

Aortic aneurysms are a rare condition in children. Here we report the occurrence of aortic aneurysms in 5 children with Wiskott-Aldrich syndrome (WAS). Three patients had a WAS score of 4, and 2 patients had a WAS score of 5, but autoimmunity was only present in 1 patient. Discovery was fortuitous in 4 cases after chest radiography or thoracic or abdominal computed tomography, which was performed to investigate unrelated symptoms; in 1 patient, thoracic pain was an alerting sign. Age at diagnosis was 10 to 16 years. Aneurysms were confined to the thoracic aorta in 4 cases and to the abdominal aorta in 1 case and were from 2 to 6 cm in size. Aortic surgery was successfully performed on the single symptomatic patient. Two other patients are alive: there has been a low progression of the aneurysm 15 years after hematopoietic stem cell transplantation in 1 patient and no evidence of progression after 12 years of follow-up without hematopoietic stem cell transplantation in the second patient. Two patients died 2 and 4 years after diagnosis from unrelated complications. A systematic retrospective search of 33 other patients with WAS for whom imaging material was available did not reveal the presence of aortic aneurysms. This unusual frequency of aortic aneurysm found in patients with WAS (5 of 38) indicates that aneurysm can be an underdiagnosed complication of WAS. It is presently unclear whether it is caused by an infectious and/or autoimmune/inflammatory process. Therefore, we suggest that aneurysms of large vessels should be systematically searched for in patients with WAS.