SETD1B-associated neurodevelopmental disorder.

BACKGROUND: Dysfunction of histone methyltransferases and chromatin modifiers has been implicated in complex neurodevelopmental syndromes and cancers. SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. Previous reports of patients with rare variants in SETD1B describe a distinctive phenotype that includes seizures, global developmental delay and intellectual disability. METHODS: Two of the patients described herein were identified via genome-wide and exome-wide testing, with microarray and research-based exome, through the CAUSES (Clinical Assessment of the Utility of Sequencing and Evaluation as a Service) Research Clinic at the University of British Columbia. The third Vancouver patient had clinical trio exome sequencing through Blueprint Genetics. The fourth patient underwent singleton exome sequencing in Nantes, with subsequent recruitment to this cohort through GeneMatcher. RESULTS: Here we present clinical reports of four patients with rare coding variants in SETD1B that demonstrate a shared phenotype, including intellectual disability, language delay, conserved musculoskeletal findings and seizures that may be treatment-refractory. We include supporting evidence from next-generation sequencing among a cohort of paediatric patients with epilepsy. CONCLUSION: Rare coding variants in SETD1B can cause a diagnosable syndrome and could contribute as a risk factor for epilepsy, autism and other neurodevelopmental phenotypes. In the long term, some patients may also be at increased risk for cancers and other complex diseases. Thus, longitudinal studies are required to further elucidate the precise role of SETD1B in neurodevelopmental disorders and other systemic disease.

Imaging Acute Airway Obstruction in Infants and Children.

Acute airway obstruction is much more common in infants and children than in adults because of their unique anatomic and physiologic features. Even in young patients with partial airway occlusion, symptoms can be severe and potentially life-threatening. Factors that predispose children to airway compromise include the orientation of their larynx, the narrow caliber of their trachea, and their weak intercostal muscles. Because the clinical manifestations of acute airway obstruction are often nonspecific, clinicians often rely on the findings at imaging to establish a diagnosis. Several key anatomic features of the pediatric airway make it particularly susceptible to respiratory distress, and the imaging recommendations for children suspected of having acute airway obstruction are presented. Although cross-sectional imaging may be helpful, the diagnosis can often be established by using radiographs alone. Radiographs of the chest and upper airway should be routinely acquired; however, for the child who is in severe distress, a single lateral radiographic view may be all that is necessary. The purpose of this article is to provide an imaging approach to acquired causes of acute airway obstruction in children, including (a) abnormalities affecting the upper portion of the airway, such as croup, acute epiglottitis, retropharyngeal infection, and foreign bodies, and (b) abnormalities affecting the lower portion of the airway, such as asthma, bronchiolitis, and foreign bodies. It is essential that the radiologist recognize key imaging findings and understand the pathophysiologic features of acute airway obstruction because in most cases, when the cause is identified, the condition responds well to prompt management.

Pearls for Interpreting Computed Tomography of the Cervical Spine in Trauma.

The high morbidity and mortality associated with cervical spine injuries makes identification and classification essential. It is important to have a systematic approach to evaluation, especially in the trauma setting with other distracting injuries. Understanding the anatomy and biomechanics enables rapid and accurate interpretation of images. In severe trauma and in patients with rigid spinal disease, the classic patterns of injury may be difficult or impossible to recognize. This article provides an approach to acquiring and interpreting cervical spine images in the setting of acute trauma and reviews the classic patterns of injury.