Recent Submissions

  • Paediatric family activation rapid response (FARR) in tertiary healthcare organisations: Protocol for an online, multi-lingual, application (app) intervention development study

    Marufu, Takawira C.; Taylor, Nicola; Cresham Fox, Shannon; Boardman, Rachel; Manning, Joseph C. (2023)
    Introduction At least 85% of unplanned admissions to critical care wards for children and young people (CYP) are associated with clinical deterioration. CYP and their families play an integral role in the recognition of deterioration. The Paediatric Critical Care Outreach Team (PCCOT) supports the reduction of avoidable harm through earlier recognition and treatment of the deteriorating child, acting as a welcome conduit between the multiprofessional teams, helping ensure that CYP gets the right care, at the right time and in the right place. This positions PCCOT well to respond to families who call for help as part of family activation. Aim This protocol details the methods and process of developing a family activation rapid response online application. Methods This is a single-centre, sequential, multiple methods study design. Firstly, a systematic review of the international literature on rapid response interventions in paediatric family activation was conducted. Findings from the review aimed to inform the content for next stages; interviews/ focus groups and experience-based co-design (EBCD) workshops. Participants: parents / caregivers whose children have been discharged or admitted to an acute care hospital and healthcare professionals who care for paediatric patients (CYP). During interviews and workshops participants’ opinion, views and input will be sort on designing a family activation rapid response online-app, detailing content, aesthetics, broad functionality and multi-lingual aspects. Further areas of discussions include; who will use the app, access, appropriate language and terminology for use. A suitable app development company will be identified and will be part of the stakeholders present at workshops. Data obtained will be used to develop a multi-lingual paediatric family activation rapid response web based application prototype.
  • Interventions for supporting parents of infants requiring neonatal inter-hospital transport: A systematic review

    Mason, Libuse; Marufu, Takawira C.; Manning, Joseph C. (2023)
    Background Neonatal inter-hospital transport is associated with heightened stress for parents whose needs may remain unmet around this time. Aim To identify interventions which are used to support parents whose infants require neonatal inter-hospital transport. Study Design A systematic literature review approach was used. Six online databases (CINAHL, EMBASE, EMCARE, Medline, PsycINFO, Web of Science) were searched up to February 2022. The eligibility criteria included interventional studies published in the English language. Methodological quality was assessed by the Critical Appraisal Skills Programme checklists. Data were extracted using a predefined framework and synthesized narratively because of heterogeneity of reported outcomes. Results A total of 671 articles were screened, with five meeting the eligibility criteria. Three interventions were reported within the five studies: a communication-based intervention before transport represented by 223 parents in one study, Kangaroo Care during transport, which was carried out with 136 infants in three studies, and video calls after transport evaluated by one study in seven parents versus a control group. The effectiveness of the interventions could not be reliably determined. Neonatal nurses were the main providers of all the interventions pre-, peri-, and post-transport. Conclusion Limited evidence of mixed quality and inconsistent outcome measurements is available. Future research should focus on developing a contemporary intervention, determining the optimum timing for its implementation, and evaluating it using a robust study design. Relevance to Clinical Practice Neonatal nurses need to be aware of the importance of their role in supporting parents through the distressing time of neonatal transport.
  • Effectiveness of preventative care strategies for reducing pressure injuries (PIs) in children aged 0-18 admitted to intensive care: A systematic review and meta-analysis

    Setchell, Bradley; Marufu, Takawira C.; Manning, Joseph C.
    Introduction: The development and prevention of pressure injuries is a complex phenomenon, dependent on a wide variety of extrinsic and intrinsic risk factors. Children with critical illness form an extremely vulnerable patient group with an exceptionally high risk of immobility-related and medical device-related pressure injuries. Recent reviews on this subject matter largely been focused on adult patients. The aim of this review is to systematically synthesise the evidence on the most effective interventions to prevent pressure injury development in children admitted to intensive care. Methods: Four electronic databases; CINAHL, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched. Studies were screened at three stages, title, abstract, and full text against the inclusion and exclusion. Quality appraisal was conducted using the Joanna Briggs Institute Critical Appraisal Tools and two authors independently extracted study data from included studies using a predesigned data collection form. A meta-analysis was performed using RevMan 5. Results: After removal of duplicates, twenty studies met the inclusion criteria. Observed interventions included; use of risk assessment tool, preventative skin regimes, nutrition, repositioning, support surfaces, medical devices care, and staff education and training. A bundle intervention approach was used to implement pressure ulcer preventative strategies. Meta-analysis demonstrated an associated 51% potential reduction in pressure injury post intervention (pooled OR 0.49 (95% confidence Interval (CI) 0.39 – 0.62) P < 0.0001). Conclusion: Pressure injury preventative strategies are more likely to reduce the number and severity of pressure injuries. Paediatric nurses are pivotal members of the direct care multidisciplinary team with unique expertise and influence over the risk assessment, implementation and maintenance of pressure injury preventative strategies for children admitted to intensive care.
  • Chapter 23: Dermatology

    Ravenscroft, Jane; Srinivasan, Jothsana (2022)
    After reading this chapter you should be able to assess, diagnose and manage: • atopic eczema • skin infections • drug eruptions • urticaria • skin manifestations of systemic disorders • ectodermal dysplasia and epidermolysis bullosa • birth marks, neurocutaneous lesions
  • How is oral isotretinoin prescribed for the treatment of acne vulgaris? Results from a UK dermatology clinical trials network (UKDCTN) and British dermatological nursing group (BDNG) survey of health professionals

    Moledina, Zahra; Ravenscroft, Jane (2023)
    We undertook a survey of UK healthcare professionals through the UK Dermatology Clinical Trials Network and British Dermatological Nursing Group to understand clinicians' routine practice of prescribing oral isotretinoin for treatment of acne vulgaris. We also wanted to understand clinicians' experiences and views on prescribing low daily dose regimens. Overall, the survey showed that clinicians adopted a patient-centred approach when deciding isotretinoin dosing. The rationale for using a low-dose regimen varied, but was focused on patient wellbeing during treatment. Some clinicians were concerned that use of a low-dose regimen could be less effective and lead to longer treatment durations. The survey results will be useful to inform a clinical trial investigating the effectiveness and safety of low daily dose isotretinoin for the treatment of acne. Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail:
  • Cost-effectiveness of topical pharmacological, oral pharmacological, physical and combined treatments for acne vulgaris

    Wood, Damian; Ravenscroft, Jane (2022)
    BACKGROUND: Acne vulgaris is a common skin condition that may cause psychosocial distress. There is evidence that topical treatment combinations, chemical peels and photochemical therapy (combined blue/red light) are effective for mild-to-moderate acne, while topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy are most effective for moderate-to-severe acne. Effective treatments have varying costs. The National Institute for Health and Care Excellence (NICE) in England considers cost-effectiveness when producing national clinical, public health and social care guidance., AIM: To assess the cost-effectiveness of treatments for mild-to-moderate and moderate-to-severe acne to inform relevant NICE guidance., METHODS: A decision-analytical model compared costs and quality-adjusted life-years (QALYs) of effective topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, from the perspective of the National Health Service in England. Effectiveness data were derived from a network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion., RESULTS: All of the assessed treatments were more cost-effective than treatment with placebo (general practitioner visits without active treatment). For mild-to-moderate acne, topical treatment combinations and photochemical therapy (combined blue/red light) were most cost-effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, and oral isotretinoin were the most cost-effective. Results showed uncertainty, as reflected in the wide confidence intervals around mean treatment rankings., CONCLUSION: A range of treatments are cost-effective for the management of acne. Well-conducted studies are needed to examine the long-term clinical efficacy and cost-effectiveness of the full range of acne treatments. Copyright © 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
  • Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis

    Ravenscroft, Jane (2020)
    BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations., OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation., METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing., RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0.004), and hand deformities (P < 0.001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype., CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown. Copyright © 2019 British Association of Dermatologists.
  • Adolescent acne vulgaris: Current and emerging treatments

    Ravenscroft, Jane (2023)
    Acne vulgaris is one of the commonest inflammatory skin diseases seen worldwide, affecting all ethnicities and races, with a peak prevalence between age 15 years and 20 years. The burden of this condition, and the resulting clinical and psychological sequelae, is substantial. The visual appearance of acne and its sequelae, including scarring and pigment changes, frequently results in psychological and social morbidity because of concerns about appearance. As understanding of the pathophysiology has evolved, approaches to achieving the optimal outcomes with effective treatment regimens continue to emerge. In the past few years, several novel therapeutics have been developed, including new agents aimed at reducing antimicrobial resistance and products with specific actions targeting retinoid receptors and androgen receptors. This Review considers the management approaches of an adolescent with acne vulgaris and reviews treatment options from the evidence base and international expert opinion. Approaches to selecting current treatments and novel and emerging treatment regimens are discussed. Copyright © 2023 Elsevier Ltd. All rights reserved.
  • A practical guide to the assessment and management of acne vulgaris

    Ravenscroft, Jane; Wood, Damian (2022)
    Acne vulgaris (syn: acne) is very common and paediatricians are in an ideal position to assess a young person and start first line treatment. This article provides a practical guide to assessing a young person with acne, giving accurate information about the condition, and starting them on a treatment journey. The association between acne and mental health is considered and advice offered regarding which treatments to prescribe, for how long, when to review, and when to refer on to dermatology. Indications for topical treatments, antibiotics, hormonal treatments and oral isotretinoin are discussed.Copyright © 2022 Elsevier Ltd
  • Identifying mental health needs of children and youth with skin disease: A systematic review of screening and assessment tools

    Ravenscroft, Jane (2022)
    BACKGROUND AND OBJECTIVES: (1) To identify patient reported outcome measures (PROMs) which have been used to screen and assess mental health symptoms in studies of youth with skin disease. (2) To critically appraise their evidence base in this population., METHODS: A systematic literature search was conducted within PubMed and PsycINFO combining search terms for pediatric populations, dermatology, screening and assessment tools, and psychological and psychiatric conditions, to identify PROMs which screened or assessed for mental health symptoms in youth with skin disease. PROMs which had undergone validation within this population were assessed for quality and evidence base using the COSMIN risk of bias tool., RESULTS: One hundred eleven PROMs which assess mental health symptoms in studies of youth with skin disease were identified. These included generic mental health scales which are extensively validated in different populations. Only one PROM, the "Skin Picking Scale-Revised" has undergone specific validation in youth with skin disease. This showed poor quality of evidence for content validity and therefore cannot be recommended., CONCLUSION: There is an urgent need to identify mental health problems early and treat proactively to improve outcomes in youth with skin disease. This review highlights the current lack of consensus around the best way to assess our patients. It is likely that existing generic mental health methods and PROMS will be appropriate for our needs. More work is required to examine the utility, feasibility, and acceptability of existing generic, validated mental health screening tools in youth with skin disease. Copyright © 2022 Wiley Periodicals LLC.
  • Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): A UK multicentre case-control diagnostic accuracy study (DIPSOC study)

    Burden-Teh, Esther; Ravenscroft, Jane (2022)
    BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults., OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis., METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping., RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84.6%, the specificity was 65.1% and the area under the curve (AUC) was 0.75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76.8%, with specificity 72.7% and AUC 0.84. The c-statistic optimism-adjusted shrinkage factor was 0.012., CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed. Copyright © 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
  • The many faces of neonatal herpes simplex infection. A case series of 4 neonates

    Mann, Jasmine; Ravenscroft, Jane (2021)
    Neonatal Herpes simplex virus (HSV) infection is a potentially life threatening disease. We describe a case series of 4 neonates who demonstrate variable presentations of neonatal cutaneous HSV and the difficulties that can occur in diagnosis. Our aim is to increase awareness of the clinical variation in neonatal HSV to facilitate early diagnosis, prompt treatment and improved outcomes.Copyright © 2021 Dermatologia Pediatrica. All rights reserved.
  • What is the demand for out-of-hours dermatology? A UK-based region-wide survey of dermatology demand and provision during the evenings and at weekends

    Mann, Jasmine; Ravenscroft, Jane (2021)
    BACKGROUND: Little is known about the demand for out-of-hours (OOH) dermatology in the UK, and this can make commissioning of acute services difficult. The East Midlands region has a population of 4.5 million people, with variable access to OOH dermatology services., AIM: We sought to investigate the provision of, and demand for, OOH dermatology services across the region with a view to informing commissioning decisions for the future., METHODS: We contacted all dermatology departments in the East Midlands region to establish what level of service was commissioned at evenings and weekends. At the sites providing any form of OOH service, we recorded all requests for advice received after 17.00 h on weekdays, or at any time during weekends and bank holidays over a 3-month period from October to December 2019., RESULTS: The OOH services provided ranged from 24 h/day cover 7 days/week at one site, to no formal provision across much of the rest of the region. In total, 125 calls were received during the study period, averaging 1 call per day on weekday evenings, and 2 calls per day at weekends and on bank holidays. Of these 125 calls, 11 patients (9%) were prioritized and seen by the on-call dermatologist on the day of referral, and 9 of these had potentially life-threatening skin conditions. A further 39 (31%) were deemed to need review within 24 h and 22 (18%) within 48 h. The remaining 42% were given appointments within 7 days or dealt with by telephone advice., CONCLUSION: The demand for OOH dermatology across the East Midlands is low, but access to timely dermatology advice is essential in some situations. Commissioning of a regional dermatology OOH service incorporating digital technology may help to improve the equity of access for all patients across the region. Copyright © 2021 British Association of Dermatologists.
  • Interventions to reduce staphylococcus aureus in the management of eczema

    Ravenscroft, Jane (2019)
    BACKGROUND: Staphylococcus aureus (S. aureus) can cause secondary infection in eczema, and may promote inflammation in eczema that does not look infected. There is no standard intervention to reduce S. aureus burden in eczema. It is unclear whether antimicrobial treatments help eczema or promote bacterial resistance. This is an update of a 2008 Cochrane Review., OBJECTIVES: To assess the effects of interventions to reduce S. aureus for treating eczema., SEARCH METHODS: We updated our searches of the following databases to October 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We searched five trials registers and three sets of conference proceedings. We checked references of trials and reviews for further relevant studies. We contacted pharmaceutical companies regarding ongoing and unpublished trials., SELECTION CRITERIA: Randomised controlled trials of products intended to reduce S. aureus on the skin in people diagnosed with atopic eczema by a medical practitioner. Eligible comparators were a similar treatment regimen without the anti-staphylococcal agent., DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were participant- or assessor-rated global improvement in symptoms/signs, quality of life (QOL), severe adverse events requiring withdrawal, minor adverse events, and emergence of antibiotic-resistant micro-organisms., MAIN RESULTS: We included 41 studies (1753 analysed participants) covering 10 treatment categories. Studies were conducted mainly in secondary care in Western Europe; North America; the Far East; and elsewhere. Twelve studies recruited children; four, adults; 19, both; and six, unclear. Fifty-nine per cent of the studies reported the mean age of participants (range: 1.1 to 34.6 years). Eczema severity ranged from mild to severe. Many studies did not report our primary outcomes. Treatment durations ranged from 10 minutes to 3 months; total study durations ranged from 15 weeks to 27 months. We considered 33 studies at high risk of bias in at least one domain. We present results for three key comparisons. All time point measurements were taken from baseline. We classed outcomes as short-term when treatment duration was less than four weeks, and long-term when treatment was given for more than four weeks. Fourteen studies evaluated topical steroid/antibiotic combinations compared to topical steroids alone (infective status: infected (two studies), not infected (four studies), unspecified (eight studies)). Topical steroid/antibiotic combinations may lead to slightly greater global improvement in good or excellent signs/symptoms than topical steroid alone at 6 to 28 days follow-up (risk ratio (RR) 1.10, 95% confidence interval (CI) 1.00 to 1.21; 224 participants; 3 studies, low-quality evidence). There is probably little or no difference between groups for QOL in children, at 14 days follow-up (mean difference (MD) -0.18, 95% CI -0.40 to 0.04; 42 participants; 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: severe adverse events were rare (follow-up: between 6 to 28 days): both groups reported flare of dermatitis, worsening of the condition, and folliculitis (325 participants; 4 studies). There were fewer minor adverse events (e.g. flare, stinging, itch, folliculitis) in the combination group at 14 days follow-up (218 participants; 2 studies). One study reported antibiotic resistance in children at three months follow-up, with similar results between the groups (65 participants; 1 study). Four studies evaluated oral antibiotics compared to placebo (infective status: infected eczema (two studies), uninfected (one study), one study's participants had colonisation but no clinical infection). Oral antibiotics may make no difference in terms of good or excellent global improvement in infants and children at 14 to 28 days follow-up compared to placebo (RR 0.80; 95% CI 0.18 to 3.50; 75 participants; 2 studies, low-quality evidence). There is probably little or no difference between groups for QOL (in infants and children) at 14 days follow-up (MD 0.11, 95% CI -0.10 to 0.32, 45 participants, 1 study, moderate-quality evidence). The subsequent results for this comparison were based on very low-quality evidence, meaning we are uncertain of their validity: adverse events requiring treatment withdrawal between 14 to 28 days follow-up were very rare, but included eczema worsening (both groups), loose stools (antibiotic group), and Henoch-Schonlein purpura (placebo group) (4 studies, 199 participants). Minor adverse events, including nausea, vomiting, diarrhoea, and stomach and joint pains, at 28 days follow-up were also rare and generally low in both groups (1 study, 68 infants and children). Antibiotic resistance at 14 days was reported as similar in both groups (2 studies, 98 infants and children). Of five studies evaluating bleach baths compared to placebo (water) or bath emollient (infective status: uninfected (two studies), unspecified (three studies)), one reported global improvement and showed that bleach baths may make no difference when compared with placebo at one month follow-up (RR 0.78, 95% CI 0.37 to 1.63; 36 participants; low-quality evidence). One study showed there is probably little or no difference in QOL at 28 days follow-up when comparing bleach baths to placebo (MD 0.90, 95% CI -1.32 to 3.12) (80 infants and children; moderate-quality evidence). We are uncertain if the groups differ in the likelihood of treatment withdrawals due to adverse events at two months follow-up (only one dropout reported due to worsening itch (placebo group)) as the quality of evidence was very low (1 study, 42 participants). One study reported that five participants in each group experienced burning/stinging or dry skin at two months follow-up, so there may be no difference in minor adverse events between groups (RR 1.00, 95% CI 0.35 to 2.87, 36 participants, low-quality evidence). Very low-quality evidence means we are also uncertain if antibiotic resistance at four weeks follow-up is different between groups (1 study, 80 participants <= 18 years)., AUTHORS' CONCLUSIONS: We found insufficient evidence on the effects of anti-staphylococcal treatments for treating people with infected or uninfected eczema. Low-quality evidence, due to risk of bias, imprecise effect estimates and heterogeneity, made pooling of results difficult. Topical steroid/antibiotic combinations may be associated with possible small improvements in good or excellent signs/symptoms compared with topical steroid alone. High-quality trials evaluating efficacy, QOL, and antibiotic resistance are required. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
  • Extensive epidermal skin loss secondary to HSV type one: Neonatal management challenges

    Calthorpe, Rebecca J.; Spencer, Emma; Ravenscroft, Jane; Tang, Ting S.; Deorukhkar, Anjum (2019)
    We describe a rare case of a preterm neonate presenting at birth with extensive epidermal skin loss of over 90% due to disseminated herpes simplex virus type one infection. Differential diagnosis included aplasia cutis and epidermolysis bullosa. Serum PCR and mouth swabs confirmed HSV type one, and the patient required three weeks of treatment with intravenous aciclovir, followed by oral aciclovir. We describe the management challenges and give practical solutions applicable to the care of a neonate presenting with widespread skin loss due to any aetiology. Copyright © 2019 Rebecca J Calthorpe et al.
  • Homozygous loss-of-function mutations in AP1B1, encoding beta-1 subunit of adaptor-related protein complex 1, cause MEDNIK-like syndrome

    Devadason, David; Ravenscroft, Jane; Suri, Mohnish (2019)
    MEDNIK syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma) is an autosomal-recessive disorder caused by bi-allelic mutations in AP1S1, encoding the small sigma subunit of the AP-1 complex. Central to the pathogenesis of MEDNIK syndrome is abnormal AP-1-mediated trafficking of copper transporters; this abnormal trafficking results in a hybrid phenotype combining the copper-deficiency-related characteristics of Menkes disease and the copper-toxicity-related characteristics of Wilson disease. We describe three individuals from two unrelated families in whom a MEDNIK-like phenotype segregates with two homozygous null variants in AP1B1, encoding the large beta subunit of the AP-1 complex. Similar to individuals with MEDNIK syndrome, the affected individuals we report display abnormal copper metabolism, evidenced by low plasma copper and ceruloplasmin, but lack evidence of copper toxicity in the liver. Functional characterization of fibroblasts derived from affected individuals closely resembles the abnormal ATP7A trafficking described in MEDNIK syndrome both at baseline and in response to copper treatment. Taken together, our results expand the list of inborn errors of copper metabolism. Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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