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A rise in the current trend of corrosive substance attacks have been reported in the UK, causing devastating effects on victims. The optimal management of these patients requires the specialist skills of the burn multidisciplinary team (MDT) to address the resulting physical and psychological trauma experienced. However, burn care must commence in the pre-hospital setting. The public and first responders are invaluable resources in helping to limit the adverse effects of burns. Challenges of burn care outside the Burns Unit are not limited to the treatment of the injured patient and the rehabilitation of survivors. These challenges also encompass better education of the public and allied health professionals, as well as planning strategies to reduce the incidence of acid attacks. Prevention is always better than cure. This paper discusses the broadening of the MDT to improve outcomes in acid attacks by exploring the wider roles of the public, media, emergency services, police, legislation and better education.

School closures were one of the earlier actions taken as the world tried to contain the COVID-19 outbreak, a decision impacting nearly three-fourths of the learners worldwide. One year into the pandemic, over 200 million students still faced disruptions to their education. Nearing the end of another academic year that has occurred entirely during the pandemic, many schools remained fully or partially closed for in-person education, altering routines and representing potential hardships to the next generation and their families. This article will explore the potential impacts of school closures on children and adolescents related to increased screen time, irregular sleep patterns, less balanced diets, learning difficulties, and changes in social interaction. In addition, we note broader familial difficulties likely accompanying the loss of the mitigating effects of schools and their associated support systems, such as parental stress and work responsibilities, loss of employment, intimate partner violence, child abuse and neglect, and parental substance abuse, which appear to have increased during the pandemic. Considering what is known about the impact from previous natural catastrophes, the populations at risk, and the early but not yet definitive data from the current pandemic, we stress the urgent need for robust data as we prepare for a new academic year in the Northern Hemisphere. Although we currently lack consistent and complete data, signs for concern include a rise in pediatric emergency room visits for mental health and substance use issues in many parts of the world. This paper aims to stimulate a discussion about the potential mental health effects of school closures for children and adolescents in the context of a pandemic.

Cardiac point-of-care ultrasound (POCUS) is a quick and accurate tool to assess a patient's cardiovascular and hemodynamic status by measuring the E-point septal separation (EPSS) and left ventricular ejection fraction. The case presented here highlights the potential for increased use of POCUS to guide resuscitation in the prehospital setting and during critical care transport. A 56-year-old male presented to a rural emergency department with chest pain and was found to have an inferior STelevation myocardial infarction (STEMI). Local helicopter air ambulance was called to transport the patient to a facility capable of cardiac catheterization. In route, the flight physician performed a cardiac POCUS exam which revealed decreased cardiac perfusion, a hypokinetic inferior wall, and overall decreased contractility. EPSS was measured at 0.77cm, indicating moderate left ventricular ejection fraction (LVEF) reduction. A cardiac left ventriculogram later confirmed a 40% ejection fraction as well as wall motion abnormalities of the inferior wall. The patient was found to have 100% occlusion of the right coronary artery that was revascularized with balloon angioplasty and a drug-eluting stent. He ultimately did well and was discharged home.

Sotos syndrome is an overgrowth-intellectual disability (OGID) syndrome caused by NSD1 pathogenic variants and characterized by a distinctive facial appearance, an intellectual disability, tall stature and/or macrocephaly. Other associated clinical features include scoliosis, seizures, renal anomalies, and cardiac anomalies. However, many of the published Sotos syndrome clinical descriptions are based on studies of children; the phenotype in adults with Sotos syndrome is not yet well described. Given that it is now 17 years since disruption of NSD1 was shown to cause Sotos syndrome, many of the children first reported are now adults. It is therefore timely to investigate the phenotype of 44 adults with Sotos syndrome and NSD1 pathogenic variants. We have shown that adults with Sotos syndrome display a wide spectrum of intellectual ability with functioning ranging from fully independent to fully dependent. Reproductive rates are low. In our cohort, median height in adult women is +1.9 SD and men +0.5 SD. There is a distinctive facial appearance in adults with a tall, square, prominent chin. Reassuringly, adults with Sotos syndrome are generally healthy with few new medical issues; however, lymphedema, poor dentition, hearing loss, contractures and tremor have developed in a small number of individuals.

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Purpose The LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. Methods We assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. Results There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. Conclusion People with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population.

Introduction Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury-related factors, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibody formation and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-transplant management strategies influence immunological outcome following VCA. Methods A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-transplant, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis. Results The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients were sensitised prior to reconstructive transplantation with an 80%%incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies. Conclusions Currently employed acute management strategies may predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. To determine whether association between pre-transplant management and outcomes exists, further refinement of international registries is required.

Women who inherit a mutated copy of the BRCA gene have a higher lifetime risk of developing breast cancer. No large epidemiological studies exist looking at BRCA mutation carriers in UK populations. All patients with BRCA1/BRCA2 mutation identified between 1995 and 2015 were included. Individuals were identified from a prospectively gathered data base. Genetics case-notes were obtained and retrospective analysis performed. 581 female BRCA mutation carriers were identified with a median age of 34 (18-81) at the time of testing. Of the 301 women who underwent diagnostic testing (symptomatic) 246 had been diagnosed with breast cancer, 89 with ovarian cancer and 37 had both at time of testing. Median age at diagnostic test was 51 (25-81). 33% of women underwent risk-reducing mastectomies (RRM); median age at surgery 45. This compares with 37% of women in this diagnostic group who underwent Risk-reducing bilateral salpingo-oopherectomies (RRBSO) at a median age of 46. Two hundred and eighty women underwent predictive testing (family history, asymptomatic), median age 36 (18-81). 34% of women in this predictive group underwent RRM, median age 37. There was a 29% uptake of RRBSO (median age 44 years). Fifteen women (5%) developed breast cancer after being tested; none of these had undergone RRS. This unique study of all BRCA mutation carriers in Wales shows considerable variation in uptake of RRS. The decision to undergo RRS is complex and involves a number of factors, including a woman's age and life stage. As BRCA testing becomes more frequent and more gene mutation carriers are identified there will be significant implications for service allocation, screening demands, and provision of risk-reducing surgery for this high-risk patient group.

Clinical Genetics services provide a diagnostic, counselling and genetic testing service for children and adults affected by, or at risk of, a genetic condition, most of which are rare, and/or genetically heterogeneous. Appropriate triage of referrals is crucial to ensure that the most urgent referrals are seen as quickly as possible, without negatively impacting the waiting times of less urgent cases. We aimed to examine triage practice in six Clinical Genetic centres across the United Kingdom and Ireland. Thirteen simulated referrals were drafted based on common referrals to Clinical Genetics. Copies of each referral were forwarded to each centre, where 10 nominated clinicians were asked to triage each referral. Triaged referrals were returned to the coordinating author for analysis. An electronic questionnaire was contemporaneously completed by clinical leads in each unit to gather local demographic details and local operating procedures relevant to triage. Widespread inconsistencies were noted both within and between units, with respect to the acceptance of referrals to the services, prioritisation and designated clinic type. Referral rates, staffing levels and waiting lists varied widely between units. Inconsistencies observed between units are likely influenced by a number of factors, including staffing levels, referral rates and average family size. Inconsistency within units likely reflects the complex nature of many Clinical Genetic referrals, and triage guidelines should help improve decision-making in this setting.

Breast cancer is the commonest cancer affecting women. A family history of breast cancer increases a woman's lifetime risk of developing the disease. Most of the genetic risk is due to low-risk and moderate-risk susceptibility alleles rather than high-penetrance genes such as BRCA1 and BRCA2 . Mutations in these two tumour suppressor genes only account for about 2% of all breast cancers. Female carriers of BRCA gene mutations have a high lifetime risk of developing breast and ovarian cancer and male carriers have an increased risk of prostate and breast cancer. Women with a significant family history of breast cancer should be referred to their local cancer genetics service for a formal cancer genetics risk assessment, discussion of risk management options such as surveillance and risk-reducing surgery and consideration of genetic testing. If a BRCA gene mutation is identified in a family, predictive testing can be offered to unaffected family members to clarify risks and help with risk management decisions. In the future, BRCA mutation carriers are likely to be offered different surgical management and/or first-line chemotherapeutic agents as treatment for cancer and one day chemoprevention agents may also be available.

It is well-recognised that receipt of cancer genetic risk information can evoke a mix of both positive and negative emotional responses. Objective risk itself is not necessarily predictive of emotional response to receipt of risk information and the Cue Adaptive Reasoning Account (CARA; Renner, 2004) suggests that that the degree to which level of risk is consistent with expectations may influence emotional responses. This paper reports a thematic analysis of the free-text data structured around responses to the three risk labels: average, moderate or high. Data is reported from both 123 women and 15 men, including those with a past or current cancer diagnosis. Reactions to risk information appear to be dependent upon participants' pre-conceived expectations about their level of cancer risk. Many average risk respondents questioned the accuracy of their result, whereas high risk information was often expected. Findings are discussed in relation to the CARA model and clinical implications.

Many individuals receiving genetic counseling are healthy with no need for clinical cancer services. We have recently relocated our cancer genetic clinic to a small house on the outskirts of a hospital site which incorporates many elements proven to be important in creating a "well-being" environment. This study explored participants' perceptions of such an environment. Eleven semi-structured telephone interviews were conducted with women who had attended the new cancer genetic clinic. All were at high risk of familial cancer, five were gene carriers and three had a personal diagnosis of cancer. The new clinic was perceived to be less medical and more relaxing than other clinics, encouraged other family members to attend in support of the attendee and did not appear to impede information comprehension. The importance of not being made to feel like an ill patient was apparent. A desire for a quiet area allowing time for reflection whilst waiting for, and following, counseling was identified. A poorly designed counseling area could reduce the quality of the interaction between patient and counselor. Consideration of specific environmental design features may promote individuals' well-being and make those attending genetic counseling feel less like "patients." Larger studies should seek to explore further the potential associations between factors such as environmental design, psychological well-being and comprehension of risk information.

Women who inherit a mutated copy of the BRCA-1 or BRCA-2 genes have a higher lifetime risk of developing breast cancer. There have been no large epidemiological studies looking at BRCA-positive patients in the UK.

Testing cancers for mismatch repair (MMR) gene defects assists selection of families for genetic testing for cancer predisposing Lynch syndrome. Performing MMR tumour testing without consent is debated, though little empirical work has been undertaken. We address this by examining the significance of testing for those who have consented without prior genetic counselling, particularly their ‘accounts’ of testing via displays of knowledge and responsibility. Semi-structured interviews were conducted with participants recruited from a UK genetics service. Participants had difficulties in formulating the benefits of testing when consent was facilitated by a relative or by mail. Discourse analysis revealed that in the absence of specific or accurate understandings of tumour testing, participants displayed responsibility towards themselves and others by generalising and diminishing the implications of testing. Within the framework of ‘genetic responsibility’, MMR tumour testing seems less important in participants’ accounts compared to more definitive genetic testing. If facilitating genetic knowledge and responsibility are goals of genetic testing then developing appropriate consent procedures for MMR tumour testing is an important consideration. Further research is required to differentiate whether genetic counselling is a precondition for enacting genetic responsibility or whether intrinsic differences between types of testing make the concept less relevant.

A 54 year old man presented with numerous cutaneous schwannomas, cranial nerve lesions, and spinal cord lesions, but no evidence of vestibular nerve involvement. There was no family history of neurocutaneous lesions. To help discriminate between the various possible diagnoses in this patient, molecular analysis of two cutaneous schwannomas was undertaken. An identical point mutation in the NF2 gene in the two anatomically distinct tumours was found, confirming this as a case of NF2 mosaicism.

Families with autosomal dominant frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALS) have previously been linked to a locus on chromosome 9p21. We describe the clinical phenotype and pathology of a large family with autosomal dominant FTD/ALS with nine affected members originating from Gwent in South Wales, UK. We also further refine the locus on chromosome 9p21 using a haplotype sharing approach and assess heterogeneity in 9p21 linked families. Within this family, affected individuals present with either FTD or ALS or both diseases simultaneously. In addition there was marked phenotypic variation including ataxia, Parkinsonism, psychosis and visuo-spatial cognitive deficits. The pathological features of the three cases described were consistent with type 2 FTD pathology, as previously reported in similar families. However, we also report distinctive cerebellar and glial pathology and a significant proportion of TDP-43 negative inclusions. No mutations in known genes for FTD or ALS were found. We identified a large 4.8-megabase haplotype on chromosome 9p21, which was shared by all affected family members. This haplotype overlaps and limits the previously reported FTD/ALS linkage region on chromosome 9p21. Sequencing of this region did not identify any evidence of a pathogenic exonic mutation. This suggests that the pathogenic change affects non-coding DNA and that the disease is caused by variation in gene or protein expression.

Objectives:To characterise the neuropathological phenotypes of two affected individuals from a family with an unusual clinical phenotype resembling motor neurone disease and dementia. Methods:Histological sections of cerebral cortex, basal ganglia, brain stem, cerebellum, and spinal cord were stained with haematoxylin-eosin, luxol fast blue, silver stains, anti-tau, anti-ubiquitin, anti-α-synuclein, and anti-neurofilament. Results:Numerous ubiquitin positive, tau and α-synuclein negative intraneuronal inclusions were present in the cerebral cortex (particularly within the dentate gyrus), cerebellar cortex, brain stem, and spinal cord. The cerebellar ubiquitinated inclusions were located in the proximal dendrite of the Purkinje cells. Loss of Purkinje cells and occasional silver and neurofilament positive axonal swellings (torpedoes) were also seen within the cerebellar cortex. The main difference between the two cases was the severity of the spinal cord involvement: no significant pathology was present within one, but obvious motor neurone disease within the other. Conclusions:The clinical and neuropathological findings in this family are best described as an example of familial motor neurone disease with dementia. Intraneuronal ubiquitin inclusions together with agyrophilic, neurofilament positive torpedoes were present within the cerebellar cortex, both previously unrecognised findings in this group of diseases.

Sotos syndrome is a childhood overgrowth syndrome characterized by a distinctive facial appearance, height and head circumference >97th percentile, advanced bone age, and developmental delay. Weaver syndrome is characterized by the same criteria but has its own distinctive facial gestalt. Recently, a 2.2-Mb chromosome 5q35 microdeletion, encompassing NSD1, was reported as the major cause of Sotos syndrome, with intragenic NSD1 mutations identified in a minority of cases. We evaluated 75 patients with childhood overgrowth, for intragenic mutations and large deletions of NSD1. The series was phenotypically scored into four groups, prior to the molecular analyses: the phenotype in group 1 (n=37) was typical of Sotos syndrome; the phenotype in group 2 (n=13) was Sotos-like but with some atypical features; patients in group 3 (n=7) had Weaver syndrome, and patients in group 4 (n=18) had an overgrowth condition that was neither Sotos nor Weaver syndrome. We detected three deletions and 32 mutations (13 frameshift, 8 nonsense, 2 splice-site, and 9 missense) that are likely to impair NSD1 functions. The truncating mutations were spread throughout NSD1, but there was evidence of clustering of missense mutations in highly conserved functional domains between exons 13 and 23. There was a strong correlation between presence of an NSD1 alteration and clinical phenotype, in that 28 of 37 (76%) patients in group 1 had NSD1 mutations or deletions, whereas none of the patients in group 4 had abnormalities of NSD1. Three patients with Weaver syndrome had NSD1 mutations, all between amino acids 2142 and 2184. We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes.