Issue 22 – Summer 2013

Ethical and policy issues in genetic testing and screening of children American Academy of Paediatrics, American College of Medical genetics and genomics Pediatrics 2013 131 620–622. With rapid growth in both genetic knowledge and consumer interest, the genetic testing and genetic screening of children are now commonplace. The decisions about whether to offer these tests should be driven by the best interests of the child. The growing evidence regarding the psychosocial and clinical effects of such testing and screening should inform best practice. This policy statement represents recommendations developed collaboratively by the American Academy of Pediatrics and the American College of Medical genetics and genomics. They apply to many of the scenarios in which genetic testing and screening may occur, including: diagnostic testing, newborn screening, carrier testing, predictive genetic tests, histocompatibility testing, adoption, disclosure, and direct-to-consumer testing. CoMMENtAry for children who present with clinical features of genetic illnesses or with a family history of a genetic condition, paediatric endocrinologists have an increasing number of genetic tests available in our clinics, even without having to consult with our medical genetics colleagues. More and more, we are put under pressure to perform these tests by families. These recommendations from the uSA are therefore timely and will be very valuable reading for many paediatricians worldwide. In addition to the wide range of scenarios described above, the authors provide two important general recommendations, which most paediatricians would no doubt whole-heartedly endorse. first, that the decisions regarding the use of testing should be driven by the best interests of the child. Secondly, that genetic testing is best offered in the context of genetic counselling. A key strength of these recommendations is that they are informed by the published evidence regarding the psychosocial, clinical and reproductive harm and benefit of genetic testing and screening, which was comprehensively reviewed and published at the same time (ross et al. 2013 Genetics in Medicine 15 234–245). Evidence on key issues such as informed consent or assent, voluntary agreement, privacy and confidentiality is presented and interpreted. An interesting distinction is made between ‘predictive’ testing, for mutations that will almost certainly give rise to disease, typically childhood-onset conditions, versus ‘predispositional’ testing, for mutations with incomplete penetrance that may never become manifest, such as adult-onset cancer syndromes. Société Française d’Endocrinologie-Diabétologie Pédiatrique (SFEDP) SfEDP, the french Society for Paediatric Endocrinology and Diabetology, was founded in 1996 as a part of the french Society of Paediatrics and currently has 196 members. The President and Secretary are regis Coutant (Angers) and Agnes linglart (Paris) respectively. unlike many other national societies, SfEDP is not organised around multisite collaborative working groups, but supports the development of reference centres for the diagnosis and management of rare paediatric endocrine diseases. These are centres for rare growth diseases (J leger, robert Debré Hospital, Paris), rare diseases of phosphorus and calcium metabolism (A linglart, Bicêtre university Hospital, Paris), rare diseases of hormone signalling pathways (P rodien and r Coutant, Angers university Hospital), sex differentiation disorders (P Chatelain, lyon university Hospital, and C Bouvattier, Bicêtre university Hospital, Paris), rare pituitary diseases (T Brue and r reynaud, Marseille university Hospital), Prader-Willi syndrome (M Tauber, Toulouse university Hospital) and rare adrenal diseases (J Bertherat, Cochin university Hospital, Paris). There are review publications once a year in the Quotidian du Médecin, a french journal for general practitioners. SfEDP organises a 1-day annual meeting, with outstanding workshops and meet-the-professor sessions. Each year, it supports 3–4 grants and 2–3 prizes of various sizes. Currently, the national accreditation in paediatric endocrinology is the national Certificate for Paediatric Endocrinology and Diabetology, which uses, in part, the ESPE Training Programme. for further information or to get in touch, visit www.sfedp.org or contact the SfEDP Secretariat at secretariat.sfedp@gmail.com 100 years of CAH in Sweden: a retrospective, population-based cohort study gidlöf S, falhammar H, Thilén A, von Döbeln u, ritzén M, Wedell A & nordenström A the Lancet diabetes & Endocrinology, Early online Publication, 28 february 2013 ConTEXT: The authors aimed to assess the effect of historical medical improvements in managing patients with congenital adrenal hyperplasia (CAH) and of neonatal screening in Sweden. METHoDS: Data sources, including the registry at the Swedish national Screening laboratory, were used to identify patients with CAH for this retrospective, population-based cohort study. The authors collected data from 2010/2011. They also identified patients via the neonatal screening programme, late-diagnosed patients reported to the laboratory, and patients who underwent genetic analysis or were known to the authors through clinical contacts. rESulTS: 606 patients with the disorder, born between 1915 and 2011, were identified. The CYP21a2 genotype was known in 490 patients (81%). The female-to-male ratio was 1.25 in the whole cohort, but close to 1 in patients detected by screening. There was a sharp increase in diagnoses in the 1960s and 1970s. After the introduction of neonatal screening (1986), the proportion of patients with the salt-wasting form increased in both sexes, from 114 (47%) of 242 individuals between 1950 and 1985 to 165 (57%) of 292 individuals between 1986 and 2011 (P=0.038). Before 1970, 5–10 children were missed annually. ConCluSIon: The authors found that, contrary to current belief, boys and girls with salt-wasting CAH were equally missed clinically. Screening improved detection of the salt-wasting form in both sexes, saving lives in boys as well as girls. The non-classic form was diagnosed more often in females, explaining the female preponderance in this cohort. CoMMENtAry using a national screening registry containing almost 100 years of data, the authors assessed the impacts of treatment advances and of screening for CAH. It has been assumed that screening is important for detecting simple virilising CAH and salt-wasting CAH in males because ambiguous genitalia at birth already alerts to the diagnosis and anticipation of salt-wasting in females. Whilst CAH screening is adopted in many ‘developed’ countries, a high proportion of false positives can lead to parental anxiety and extra healthcare costs. Therefore, CAH screening programmes should be evaluated in terms of both mortality and morbidity reduction. Well-being, not just survival, is important, and there remain many surgical and psychological issues in relation to treatment timing, efficacy, compliance etc. This paper is important because the authors found that screening improved detection in girls as well as in boys. Contrary to received wisdom, girls with salt-wasting CAH were missed clinically as often as boys, despite a highly developed healthcare system. Apparent increases in incidence over time reflected improvements in diagnosis and increased awareness of CAH arising from healthcare improvements and the development of paediatric endocrinology as a specialty. Earlier detection of salt-wasting CAH through screening means that both sexes escape adverse effects (neonatal hyponatraemia/ hyperkalaemia/hypoglycaemia/acidosis) at this important window for brain development. Healthcare benefits are maximised by integrating molecular genetics with specialised care, and a healthcare system that collects universal data; this has been shown to be beneficial even in a ‘developing country’, such as Cuba (gonzalez et al. 2013 Clinica Chimica acta 421 73–78) 18th ESPE Winter School WInTEr SCHool rETurnED To PolAnD this year, taking place on 15–21 february at the magnificent castle Zamek Baranów, near rzeszów. The faculty comprised 25 students selected from nearly 60 applications, and 7 teachers. We gave preference to students from Poland and the surrounding countries, and were keen to build on the success of the 2012 Winter School in ukraine by encouraging further applications from east and (especially) west ukraine. our Host Co-ordinator, Artur Mazur, showed extraordinary commitment and attention to detail, so the event went very smoothly. other members of the Winter School faculty were Malcolm Donaldson (Co-ordinator; glasgow, uk) and John gregory (Cardiff, uk), Christa flück (Berne, Switzerland), Angela Hübner (Dresden, germany) and Margaret Zacharin (Melbourne, Australia). We were also joined by David Metreveli, next year’s Host Co-ordinator (Tbilisi, georgia). As usual, the 5-day course covered all main aspects of paediatric endocrinology and diabetes. The format was a combination of interactive plenary lectures and small group sessions involving student case presentations, student research proposal rehearsals, and the everpopular 1½-hour sessions on teachers’ cases. The research component of Winter School was led for the third time by Christa flück and consisted of evening sessions on how to do research and audit, critical evaluation of two papers sent out by Christa beforehand, and presentation of 10 selected student research or audit projects to the plenum. The excursion was to the town of Sandomierz, where we walked a famous underground route, attended a church organ concert, and visited an armoury to learn about weapons through the ages, from a young man dressed as a crusader. We finished by climbing the town tower – a very stimulating if cold (–10°C) experience! Back at the castle we enjoyed a firework display and a meal in a cave with a three-piece band, punctuated by a visit from two gate-crashing ‘soldiers’ to ravish one of the students (‘a virgin’) and put the Winter School Co-ordinator in the stocks, before challenging faculty members to rescue their hapless colleagues! The meeting was another resounding success with a particularly high standard of student cases and research presentations, and the best ever student feedback for the research sessions. This is a huge credit to Christa flück, and a fitting tribute at this, her final ESPE Winter School; she has served us brilliantly since 2009. Seven of the 25 students have since had abstracts accepted for the 9th Joint Meeting of Paediatric Endocrinology in Milan this September. I shall stand down as Co-ordinator after georgia 2014; the post will be advertised shortly. In 2015, Winter School will visit the Balkans for the first time, with Zoran gucev (Skopje, Macedonia) as Host Co-ordinator. We thank ferring Pharmaceuticals (especially their global Brand Manager Phil Boothroyd) for sponsoring our meetings, as they have done from the inception of Winter School in 1995. Malcolm Donaldson, Glasgow, uK ESPE Winter School Co-ordinator 2008–2014 In April, Ipsen informed the Regulatory Agencies of the EU, ESPE and the public of a market shortage of Increlex® (mecasermin) in the EU from early August 2013. The shortage is due to difficulties in manufacturing the active ingredient of Increlex®. These issues are not related to the safety or efficacy of Increlex® currently on the market. Ipsen is making every effort to resume a normal supply as soon as possible, but the duration of the shortage is currently unknown and resupply before the end of 2013 is not anticipated. Increlex® is recombinant human insulin-like growth factor-1 (rhIGF-1) approved for the long-term treatment of growth failure in children and adolescents of 2–18 years with severe primary IGF-1 deficiency (IGFD). Ipsen recommends that remaining product should only be used for patients who already receive Increlex®. Treatment of new patients should not start until normal supplies are re-established. There are no alternative treatment options for severe primary IGFD available in the absence of Increlex®. Ipsen recommends that physicians follow-up all patients during the offtreatment period. For patients in the European Increlex Growth Forum Database (EU-IGFD) Registry, this enforced break will provide the possibility of documenting information on the clinical consequences of treatment interruption and reintroduction, which could be extremely valuable. Ipsen has established an Advisory Board of EU clinicians, expert in the management of paediatric growth disorders, who will answer your medical management questions in an independent and confidential manner: Peter Bang (peter.bang@liu.se), Michel Polak (michel.polak@nck.aphp.fr), Martin Savage (m.o.savage@qmul.ac.uk), Joachim Woelfle (joachim.woelfle@ukb.uni-bonn.de). Book your PLACE! Winter School 2014 21–26 February, kachreti, Georgia our venue will be the friendly and intimate Ambasadori Hotel in kachreti, 85km from Tbilisi. Application forms will be available at www.eurospe.org from 1 August and the deadline for their submission is 25 october 2013. Applications will be particularly welcomed from georgia, Armenia, Azerbaijan, Turkey, countries of the Middle East, russia and ukraine