Rare SUZ12 variants commonly cause an overgrowth phenotype.

The Polycomb repressive complex 2 is an epigenetic writer and recruiter with a role in transcriptional silencing. Constitutional pathogenic variants in its component proteins have been found to cause two established overgrowth syndromes: Weaver syndrome (EZH2-related overgrowth) and Cohen-Gibson syndrome (EED-related overgrowth). Imagawa et al. (2017) initially reported a singleton female with a Weaver-like phenotype with a rare coding SUZ12 variant-the same group subsequently reported two additional affected patients. Here we describe a further 10 patients (from nine families) with rare heterozygous SUZ12 variants who present with a Weaver-like phenotype. We report four frameshift, two missense, one nonsense, and two splice site variants. The affected patients demonstrate variable pre- and postnatal overgrowth, dysmorphic features, musculoskeletal abnormalities and developmental delay/intellectual disability. Some patients have genitourinary and structural brain abnormalities, and there may be an association with respiratory issues. The addition of these 10 patients makes a compelling argument that rare pathogenic SUZ12 variants frequently cause overgrowth, physical abnormalities, and abnormal neurodevelopmental outcomes in the heterozygous state. Pathogenic SUZ12 variants may be de novo or inherited, and are sometimes inherited from a mildly-affected parent. Larger samples sizes will be needed to elucidate whether one or more clinically-recognizable syndromes emerge from different variant subtypes.

Management of Acute Contrast Reactions-Understanding Radiologists' Preparedness and the Efficacy of Simulation-Based Training in Canada.

PURPOSE: Acute radiologic emergencies, primarily severe contrast reactions, are rare but life-threatening events. Given a generalized paucity of formalized or mandated training, studies have shown that radiologists and trainees perform poorly when acutely managing such events. Moreover, skill base, knowledge, and comfort levels precipitously decline over time given the infrequent occurrence of these events during one's daily practice. The primary aim of this study was to assess radiologists' preparedness for managing acute radiologic emergencies and to determine the efficacy of a high-fidelity simulation based training model in an effort to provide a rationale for similar programs to be implemented on a provincial or national level. METHODS: This was a prospective, observational study of radiology residents and attending radiologists throughout the province who were recruited to attend a full-day simulation-based course presenting various cases of acute radiologic emergencies. Participant demographics were collected at the time of commencement of the workshop. Course materials were disseminated 4 weeks prior to the workshop, and a 17-question knowledge quiz was administered before and after the workshop. Likert-type questionnaires were also distributed to survey comfort levels and equipment familiarity. The knowledge quiz and questionnaire were redistributed at 3- and 6-month intervals for acquisition of follow-up data. RESULTS: A total of 14 attending radiologists and 7 residents attended the workshop, with all participants completing the preworkshop questionnaire and 90.5% (19 of 21) completing the post-workshop questionnaire. Participants' principle locations of practice were as follows: academic institutions (50%), community hospitals (36.9%), and private clinics (13.1%). A significant increase in knowledge was demonstrated, with average scores of 10 out of 17 (59%) and 14.5 out of 17 (85%) (P < .001) before and after the workshop, respectively. A significant increase in participants' comfort levels in recognizing acute anaphylactic reactions (3.5; 4.7, P < .001), commencing initial management for acute radiologic emergencies (3.3; 5.0, P < .001), and administering the correct dose for anaphylactic reactions (2.5; 4.8, P < .001) was also demonstrated. Moreover, participants became increasingly familiar with the contents and equipment found within contrast reaction kits (2.8; 3.8, P < .01). Repeat evaluations at 3 and 6 months found an average knowledge test score of 13.8 out of 17 (81%) and 10.8 out of 17 (64%), respectively. Comfort levels were also reassessed in recognizing acute anaphylactic reactions (4.5; 4.1), commencing initial management (4.0; 3.9) and administering the correct dose of medication (4.0; 3.7) at 3- and 6-month intervals. CONCLUSIONS: Acute radiologic emergencies are rare but life-threatening events that require rapid diagnosis and treatment to mitigate associated morbidity and mortality. Simulation-based workshops are a highly efficacious training model to increase knowledge, comfort levels, and equipment familiarity for radiologists and trainees alike; however, retraining at regular intervals is required.

A novel mutation in EED associated with overgrowth.

In a patient suspected clinically to have Weaver syndrome, we ruled out mutations in EZH2 and NSD1, then identified a previously undescribed de novo mutation in EZH2's partner protein EED. Both proteins are members of the Polycomb Repressive Complex 2 that maintains gene silencing. On the basis of the similarities of the patient's phenotype to Weaver syndrome, which is caused by de novo mutations in EZH2, and on other lines of evidence including mouse Eed hypomorphs, we characterize this mutation as probably pathogenic for a Weaver-like overgrowth syndrome. This is the first report of overgrowth and related phenotypes associated with a constitutional mutation in human EED.