6 July 2011 print
Spotlight on...
EU Policy News
Nat Pol News
ELS News
Orphanet News
New Syndromes
New Genes
Research in Action
Patient Man & Therapy
Orphan Drugs
Patients' Associations
Courses & Education
What's on?
Press & Publications
Subscribe / Unsubscribe
Search the Orphanews Europe archives:


Rare disease registries high on EUCERD's busy autumn agenda

Summer is upon us and the European Union Committee of Experts on Rare Diseases (EUCERD) is busy finalising its working calendar for the autumn before packing up for the holidays. The topic of registries for rare diseases figures high on the priority list of EUCERD and is amongst the themes on the agenda of events planned for the autumn. A workshop entitled Towards a Public-Private Partnership for Registries in the Field of Rare Diseases will gather experts in London on 4 October 2011 to define how to establish a collaboration between academics, patients, and industry to jointly create, manage, and use data for the benefit of research while fulfilling obligations from regulatory agencies. To help prepare, the 2009 report of the Rare Diseases Task Force (RDTF) on Patient Registries, based on outcomes from a 2008 workshop, has been revised and is now available. The updated report contains a list of the rare disease patient registries in Europe.

Other events planned include a workshop scheduled for 8 September 2011 gathering experts to draft the EUCERD Recommendations on Quality Criteria for National Centres of Expertise for Rare Diseases. There will also be a workshop on the Classification of Genetic Diseases scheduled for 1 December 2011, which will focus on the World Health Organization's ICD revision process. Adaptation of the principles of nomenclature and modelling in health information systems will be applied to genetic diseases.

Finally, the EUCERD is organising a joint event with EuroBioMed to take place on 4 November 2011 in Montpellier, France. Held on the last day of the three-day Rare2011 conference, the agenda will focus on Sharing Data to Improve Health Care Management for Rare Diseases with three main areas addressed:

  • Ensuring visibility of rare diseases in health information systems
  • Partnering to optimise the use of patient data to improve clinical research and health care
  • Improving access to expertise and quality health care

  • The next general meeting of the EUCERD is scheduled for 24-25 October.

    Spotlight on...
    ERA-NET PrioMedChild projects look at orphan drugs and paediatric populations

    Many of the medicines currently prescribed to children may never have been studied in paediatric populations, meaning that medicinal products are administered without precise information on dosage, potential toxicity and evidence of clinical safety and efficacy at the recommended dosages. The ERA-NET PrioMedChild (Priority Medicines for Children) is a network of eleven research funding organisations from different EU Member States working on the development of research around medicines for children. Under the umbrella of ERA-NET PrioMedChild, the national funding organisations of the Netherlands, Estonia, Finland, France, Great Britain, Italy, Latvia and Poland jointly provided funds in the order of €8 million to support the European call. The research projects were funded for three years in consortia with a minimum of three participants from at least three countries and a maximum number of 8 research groups. Regardless of its size, each collaborative consortium should have the optimal critical mass to achieve ambitious scientific goals and should clearly show the added value from working together. The ERA-NET PrioMedChild received €1.7 million from the European Commission's DG Research to set up the network and collaboration, but no funds for research. The Joint Call was funded out of national research budgets. Partnerships between research funding organisations seek to bring coherence and cooperation to national research programmes and policies on research for Priority Medicines for Children. PrioMedChild aims to contribute to ensuring more effective and safer medicines for children. At the end of 2010 seven projects were granted, the majority of which are directly related to the field of rare diseases and orphan drugs:

  • New drugs for rare diseases: cost-effectiveness modelling in cryopyrin associated periodic syndromes
  • When a disease affects only a few individuals in any nation, it can be very hard to establish the cost-effectiveness of treatments. Traditional methods to assess cost-effectiveness cannot be used because of the low number of patients. Given that expensive medications such as biologics are showing promising results in some patients with very rare diseases, it is becoming increasingly important to obtain detailed information on as many patients as possible. This promising new international collaboration aims to develop a model to evaluate both costs and (long-term) benefits in an orphan group of diseases, cryopyrin associated periodic syndromes, also known as CAPS. The same model may be used in other very rare disorders. Just a few children each year are diagnosed with one of the CAPS, a group of diseases which have inflammation as their main characteristic. Lacking any reasonable trigger such as an infection, their bodies go into full-fledged inflammation mode, producing high fevers, joint pains, skin problems and many other symptoms. In more severe cases, each attack causes damage to the brain and sensory organs, resulting in intellectual deficit, deafness and blindness. "The cost of illness can be very high in these patients, both in financial terms and in terms of their quality of life," says Genovese clinical pharmacologist Dr. Ornella Della Casa Alberighi, co-coordinator of the RaDiCEA (Rare Diseases & Cost-Effectiveness Analysis) project. (Learn more)

  • Rare diseases: use of clinical trial simulation for the choice and optimisation of study design
  • Computer modelling can be used to find the best method of performing a clinical study on a new drug. Finding the optimal study design is especially important when testing drugs in children with rare diseases, to minimise the research burden on young patients and optimise the chances of finding effective and safe treatments. Like any other drug, orphan drugs must be tested to make sure they are effective and safe, before being authorised for use on the European market. This can be difficult, because the low numbers of patients with rare diseases may not allow for the traditional model of clinical drug trials, the randomised controlled trial (RCT) in which patients are assigned at random to a study group or a control group. Statistics show that to achieve results with sufficient certainty, relatively large groups of patients are needed, often as many as several thousand. So what can be done when there are not that many patients? Will another study design predict efficacy and safety with an acceptable amount of certainty? Can it be determined in advance which study design provides the best guarantee that a trial will produce reliable results? Computer modelling may prove to be the essential tool here. This PrioMedChild project tries to find new methods of studying the safety and efficacy of drugs, in a more tailor-made fashion. Dr Catherine Cornu, who coordinates the project along with her colleagues at Université Claude Bernard (Lyon), Dr Patrice Nony and Dr Behrouz Kassai, explains, "We want to develop a model that will enable us to say: if you have this disease, and this drug aimed at this particular mechanism, then this is the study design for you. Ideally, the model would predict the best study design for any disease, but that may take many more years of research. What we do in this project will be the first steps towards that goal". Researchers from several European universities are working together within the project. They combine expertise in mathematical models, biostatistics and clinical drug trials with specific knowledge about three rare diseases: severe myoclonic epilepsy in infancy (Dravet syndrome), cystic fibrosis and lymphoblastic lymphoma. In the initial stages of the project, the researchers will aim for specific clinical targets, such as prevention of pulmonary complications in cystic fibrosis. Says Dr Cornu: "To develop our methodology, we need to focus. At first it will be one drug, with one purpose and one endpoint we can connect to our disease model. With all that in place, our group can then make a computer model to design the best clinical trial. We can simulate thousands of clinical trials with different designs and compare results: which design yields the highest precision with the shortest duration and the lowest number of patients? In these rare diseases, there is no second chance to get it right in reality, so a computer simulation can help you prepare the best possible study and give drug trials the best chance to arrive at conclusions". (Learn more)

  • A faster and better tool for clinical decisions in children with leukaemia
  • Minimal residual disease (MRD) has become a key phrase in treating leukaemia. The number of cells still within the bone marrow after an aggressive course of cytostatic treatment has been shown to be a crucial predictor of outcome. If no cells can be found, a milder treatment regime is possible. New techniques have been developed in the laboratory to measure MRD faster and more precisely. Now, via the PrioMedChild programme, they are to be tested in a multi-centre European study. Should it succeed, clinicians will have better tools to decide on the dosage of medication and the use of very expensive new medicines. Treating children with leukaemia is notoriously difficult. There are several effective cytostatic drugs, but they are also highly toxic. If the child receives too little of this medication, the disease bounds back with a vengeance. But the price of survival may be high, as there are often late effects on heart, bones, kidneys, skin and brain. During treatment, it would ideally be possible to know which children will need high doses of cytostatic drugs and who may be cured with lower doses. This has been the aim of scientists for quite some time. Explains Prof. Dr Jacques JM van Dongen of Erasmus University Medical Centre in Rotterdam: "We started to work on this subject in the 1980s, and it took us more than ten years to develop sufficiently sensitive techniques for detection of low frequencies of leukaemic cells. What we did find already, is that the number of leukaemic cells in the bone marrow after the first course of treatment, the minimal residual disease, MRD, is crucial for prognosis. If we cannot find any leukaemic cells, the disease returns in only a very few patients. In an intermediate group, where one in 1000 to 10,000 cells is malignant, the relapse rate is about 25%. With more than one in 1000 cells, there is a very high chance, about 80%, that the leukaemia will come back. We also knew from the 1970s, that low doses of chemotherapy were able to cure 35 to 40% of all children with leukaemia. So we wondered: maybe the patients in whom we could not detect any residual leukaemic cells are the ones who do not need high doses of chemotherapy? When we put this idea to the test, experts from other countries predicted disaster. But we now have more than 500 children included in our MRD study, and we proved that it is safe to leave out the intensive second course of treatment in those children who have no MRD". In the PrioMedChild project, van Dongen and his colleagues from Poland and the Czech Republic will test an approach based on recognition of protein molecules on the cell surface, the so-called 8-color flow cytometry. "Using newly developed flow cytometry software with a special statistical technique known as principal component analysis, we can recognise leukaemic cells. We use eight slightly different surface characteristics, combining them in such a way that they yield almost one hundred percent certainty". The new technique has already been tested in the detection of leukaemic cells in high concentrations. The challenge will be to show that it also works to detect 50 leukaemic cells among half a million healthy ones. "It is the proverbial needle in the haystack," van Dongen admits. "New drugs are being introduced, many of them biologicals based on antibodies against cancer cells. A sensitive and specific test for MRD may help to identify those patients who have the highest risk with conventional treatment and who may benefit most from these expensive drugs. Another great advantage will be that we collect all the primary data in all the participating centres. Because of the high levels of standardization, we can combine the primary flow cytometric data into one data base, making further scientific progress a lot easier. I think it is really fantastic what this PrioMedChild grant allows us to do". (Learn more).

  • Developing an effective treatment for childhood cancer with fewer side effects
  • Chemotherapy is frequently effective against childhood cancer, but there can be severe side-effects. Treatment may have lifelong negative consequences, because of damage to developing tissues and organs. A research team from several European countries is currently seeking a 'golden bullet' technology which will deliver drugs directly into cancer cells, thereby sparing healthy tissue. Using nanoparticles and several methods to ensure specific targeting of cancer cells, the teams hope to improve drug delivery and timing, prevent overdosing and overcome drug resistance. The researchers already have extensive experience in the use of so-called biomaterials, compounds that can be safely used within the human body. They propose to use a combination of two biomaterials (chitosan and polypyrrole) to create microscopic balls (nanospheres) containing an anti-cancer drug. Creating these nanospheres will be the task of the Paris group. These nanospheres are closed, so that toxic drugs cannot escape and damage healthy cells. The next stage in this PrioMedChild project, carried out by an INSERM team in Toulouse will be to check, by employing imaging techniques, that the drug actually remains within the little molecular balls. To unlock the nanospheres, a chemical trigger is needed, such as the amount of acid in the environment. It is a known fact that cancer cells produce more acid than normal cells. The researchers hope to utilise this property, developing new biomaterials from the combination of chitosan and polypyrrole that change their structure when they enter the acidic micro-environment of a tumor. This change opens the nanosphere, releasing the drug. To enhance selectivity of the drug delivery process, nanospheres which carry specific receptors will be developed. They will function as specific triggers to open the nanospheres. (Learn more).

    The other projects of the PrioMedChild network will look at Validating non invasive imaging of the serotonergic- and dopaminergic system and adult neurogenesis with MRI; towards a better insight in the neurobiological mechanisms underlying psychiatric disorders in the paediatric population; Paediatric Accelerator Mass Spectrometry Evaluation Research Study; and Neonatal Exposure to Excipients. These seven projects contribute to making medication use safer for paediatric populations, including children with rare conditions.
    Visit the PrioMedChild website


    EU Policy News
    Routine newborn screening for severe combined immunodeficiency urged at EU forum

    IPOPI, the International Patient Organisation for Primary Immunodeficiencies, organised its first EU PID Forum at the European Parliament in Brussels on 15 June. The forum was hosted by Member of the European Parliament Glenis Willmott (UK), and focused on severe combined immunodeficiency (SCID) newborn screening. Participants in the workshop included IPOPI representatives and other key opinion leaders on SCID newborn screening, such as leading physicians, researchers and industry representatives. The key recommendation of the workshop was that the European Union and its Member States should consider SCID a paediatric emergency and introduce SCID to the obligatory list of diseases for which newborns are routinely screened. The USA is the only country currently offering routine screening for SCID. Several concrete lines of action were identified to promote screening across Europe. A detailed report of the meeting outcomes and other key documents will be posted shortly on the IPOPI website.


    National & International Policy Developments
    The Netherlands tries out a single patient 'n-of-1 trial service’ for off-label rare disease treatments

    The marketing authorisation of medicines (registration) is linked to specific diseases, but sometimes doctors have good reasons to also prescribe a medicine for another disease. This prescription for another (non-registered) disease is called "off-label" use. In the Netherlands, expensive medicines are not reimbursed for off-label use without sufficient evidence of efficacy. The best evidence comes from large studies in many patients. However, such evidence is hard to collect when it comes to rare diseases, because there are often too few patients to carry out such large studies. In practice, therefore, Dutch patients with rare diseases frequently have to wait until studies conducted abroad indicate that an off-label medicine is effective. Or, alternatively, they have to pay for the off-label medicines themselves. If the medicines are expensive, patients might be unable to afford them. It is highly probable that similar scenarios exist for patients with rare diseases in other countries.

    In the case of chronic conditions and fast-acting medicines for symptomatic treatment, it might be justified to collect evidence of efficacy from a trial treatment of a single patient. VU University Medical Center in Amsterdam is working together with the Dutch Neuromuscular Diseases Association in the development of an n-of-1 trial service. A “n of 1” is a clinical trial involving a single patient, ie, a single case study. Through this service, patients with rare diseases would be able to receive treatment while at the same time testing the effectiveness of certain (expensive) medicines. During such an "n-of-1 trial" the physician alternately treats the patient with the off-label medicine and the medicine with which it is compared, for example, a placebo or treatment-as-usual. Rules are agreed in advance to allow for a fair comparison. The results of the trial treatment indicate whether the patient experiences benefits of the off-label medicine over and above treatment-as-usual. As series of trial treatments together bring more knowledge, these separate n-of-1 trials would be centrally coordinated and combined for analysis by an n-of-1 trial service. The current project is investigating whether such trial treatments, to be facilitated by the n-of-1 trial service, could be reimbursed by the Dutch basic health insurance. It is also examining whether the results of this type of research may be sufficient for authorities to decide on the effectiveness of an off-label medicine and its reimbursement for future patients with the rare disease in question.

    Plans for the n-of-1 trial service are presently still on the drawing board and the details are gradually being filled in. In a follow-up project, researchers hope to actually invite patients to participate in pilot trial treatments for neuromuscular diseases and eventually other diseases as well. An update on the establishment of the n-of-1 trial service will be offered in a subsequent newsletter. If you have any questions about this project, please contact Stephanie Weinreich or Charlotte Vrinten at the VU University Medical Center in Amsterdam.
    Learn more

    Health authorities agree to global management of patients with neuromuscular and related diseases in Italy
    During the 25 May session of the Permanent Conference for relations between State, Regions and Autonomous Provinces of Trent and Bolzano, an agreement was ratified, formalising the engagement of health authorities in guaranteeing, through concrete actions, the global management and appropriate pathways of health care continuity, which must be homogenous throughout Italy, for patients affected by neuromuscular diseases. This goal was achieved via the intensive work carried out by the Ministerial Conference for Neuromuscular Diseases. The enactment of this agreement will allow to overcome gaps in health care in some Italian areas and to improve quality of life for patients and their families.
    Other European news
    Web portal for Langerhans cell histiocytosis and associated syndromes launches

    A web portal for Langerhans cell histiocytosis (LCH) and associated syndromes is now available in five European languages (English, French, German, Italian and Spanish). Euro-Histio-Net is a reference network that seeks to contribute toward improved diagnostics and treatments for LCH and related syndromes, including juvenile xanthogranuloma, Erdheim-Chester disease, Rosai-Dorfman disease and associated rare histiocytoses. Histiocytoses are characterised by an abnormal proliferation of histiocytes. The network seeks to merge data from various international databases, serving as a common platform for different groups collecting information on LCH and associated syndromes. Other goals include raising awareness – both for the diseases and for the resources available for professionals and patients. Features of the portal include a map of experts around the world, information for patients, families and the public, information for physicians, scientists and other health professionals, and a special section for children. Funded by DG Sanco’s Public Health Programme and with support from various patient associations, the Euro-Histio-Net project work packages include developing the web portal, creating the web database, a “Meet the Expert” function for case presentations and information provision, a patient site that coordinates country patient association resources, the production of guidelines for diagnosis, treatment and follow-up, and languages/translation functionalities. Technical support for Arabic, Bulgarian, Dutch, Greek, Polish, Portuguese, and Swedish-language materials is being installed in order to make the information on the Euro-Histio-Net web portal as widely available as possible.
    Visit the Euro-Histio-Net web portal

    Brig navigation in Italy empowers rare diseases patients

    Tender To Nave Italia is a non-profit foundation established in 2007 by the Italian Yacht Club and Navy, which has the biggest brig worldwide, built in 1993 and based on the original 18th century design. With a 1300-square metre sail surface, it is 61-metres long and can accommodate 24 guests, in addition to the 20-person Navy crew. The foundation mission is to make concrete contributions on behalf of the most vulnerable members of society: children and adolescents with physical, psychic, and sensory disabilities and young people with family and social distress. Fostering sea navigation as an educational instrument, Nave Italia is a training ship with the capacity to facilitate projects geared toward helping young people acquire some solid life skills. Indeed, sailing navigation provides an effective model for encouraging respect for the self, others and the environment. These qualities can be measured through indicators such as self-esteem levels, which life onboard can quickly improve.

    The Mare Nostrum project was conceived by Dr Carlo Dionisi Vici, head physician for Metabolic Diseases at the Bambino Gesů Paediatric Hospital (OPBG) in Rome. A group of 10 teenagers (11-16 years old) affected by rare metabolic diseases had the possibility to sail for 5 days in the Tyrrhenian sea (from Civitavecchia to the island of Ponza and Gaeta) and to confront new challenges both individually and as a group on a daily basis and with onboard rules. The project aimed at making more independent the group of youngsters affected by rare diseases including phenylketonuria, galactosaemia, mucopolysaccharidosis type 1, Pompe disease, VLCAD fatty acid oxidation defect, citrullinaemia, and isovaleric acidaemia. Together with Commander Massimo Polacci and members of the Navy, the children onboard were followed by a team from the OPBG, including physicians, nurses and a psychologist. The children learned how to manage their therapy during cooking sessions in which they discovered the flavours and aromas of Mediterranean cuisine within the bounds of their specific diets. Days were dedicated to learning about navigation, sailing-related tasks, play and recreational activities.

    At the end of the Mare Nostrum project, “sailor diplomas” were handed to all participants by the commander, and the OPBG organised a workshop on Mass Media and Rare Diseases chaired by Pr Alberto Giovanni Ugazio, president of the Italian Society of Paediatrics, and Pr Bruno Dallapiccola, scientific director of OPBG and Italian coordinator of Orphanet. During this session, the role of media in disseminating knowledge on rare diseases was illustrated, and the responsibility of reporters for spreading sound information highlighted.

    Nowgen issues programme for 2011-2012
    Nowgen, a leading UK centre for genetics seeking to inform and improve genetic medicine via training, education, public engagement, research and innovation, has issued its Review and Programme for 2011-2012. Nowgen, working with Orphanet UK, will continue its commitment to facilitating access to high quality information on rare diseases and orphan drugs for professionals, patients and the public.
    Consult the Nowgen 2011-2012 programme

    Other International News
    New CDC report reveals sharp increase in developmental disabilities in children in the USA
    In the USA, the Centers for Disease Control and Prevention reports that developmental disabilities have risen sharply in paediatric populations (aged 3-17), including autism, blindness, hearing loss, learning disability and intellectual disability. Comparing statistics from 1997-1999 and 2006-2008, certain disabilities, especially autism, showed a very sharp increase. A need for future research to examine the factors contributing to the increase – including growing awareness of conditions – is called for, along with an examination of early intervention strategies.
    Learn more


    Ethical, Legal & Social Issues

    Schmoozing for a good cause … how forging relationships with scientists can help patient groups forward their research aims
    An interesting new paper from a researcher at the Public Policy and Center for Society and Genetics at UCLA, published in the journal Social Studies and Science, explores how a rare genetic disease patient organisation can successfully draw research to its cause by the nature of the social relationship established with scientists working in related fields. Via a series of interviews with leaders of patient groups and the scientists involved with these groups, the author examines the ways in which patient groups are able to attract - and influence - scientific research via what the author labels ‘sociability,’ ie, a close relationship established between patient organisation members and researchers through which the patient group is able to influence the research agenda. The article, entitled Generating Sociability to Drive Science: Patient Advocacy Organizations and Genetics Research, shows how “strategic manipulation” of sociability can allow a patient organisation “substantial influence” in the arena of research, although such social ties are not easily attained and “most forms of relationship-building offer [patient organisations] much less influence on research”.
    Read the PubMed abstract

    The USA is now scientifically AND politically correct when it comes to intellectual deficit
    International policy is finally catching up with terminology Orphanet implemented years ago. In the USA President Barack Obama recently signed into law S.2781. Referred to as “Rosa’s Law”, the measure officially changes references in many US Federal statutes that currently use the term “mental retardation” to refer, instead, to “intellectual disability”. Intellectual deficit or disability - scientifically and medically a more precise, accurate term - is a symptom of numerous rare conditions.
    Learn more about Rosa’s Law

    Children and biobanking: a look at ethical and legal considerations
    The use of tissue samples from children is vital to forwarding the understanding and treatment of rare diseases. A review of international ethical guidelines and legal regulations governing genetic biobanking and children addressed three core elements: permission from a legal representative; assent and dissent; and evaluation of risks, benefits and necessity. The study, published in Human Genetics, surveyed the literature to identify common ethics-related themes, providing an overview of international ethical guidelines and legal regulations. The study identifies “consent” as a major recurring topic in ethical discussion, along with “benefit”, “risk/burden” and “results”. The principle of “solidarity” is also broached with its ensuing debate of whether social obligation can be applicable to paediatric populations. The authors conclude that “the use of stored tissue samples from minors in genetic biobank research is a step away from the clinical trial paradigm, although some of its ethical concepts are still applicable. However, this shall become less so when databases will become more virtualized and contain more data and materials. In this respect, questions about who needs to have a say on the different steps of sequencing, analysis and storage will need to be answered”.
    Consult the PubMed abstract

    Patent laws for genes and genetic diagnostic methods differ between the USA and Europe
    There exist legal differences between Europe and the USA when it comes to gene and genetic diagnostics patenting. The debate over whether genes and genetic diagnostic methods should be regarded as “…inventions or subject matter eligible for patent protection, or whether they are discoveries or principles of nature, and thus excluded from patentability” is far from over. The European Patent Office (EPO) holds a gene patentable “if isolated from its natural environment” whereas in a recent case in the USA involving the Association of Molecular Pathology (AMP) and the US Patent and Trademark Office (USPTO), the USPTO invalidated seven patents claiming genes and genetic diagnostic methods held by Myriad Genetics, classifying an ‘isolated’ gene as a product of nature. Furthermore, as a paper appearing in the European Journal of Human Genetics explains, the “genetic diagnostic method claims did not survive the machine-or-transformation test in AMP versus USPTO and were regarded as laws of nature, hence unpatentable”. In contrast, such methods are not currently excluded from patentability in Europe. While the authors concede that it is “…very unlikely that the AMP versus USPTO decision will influence European patent law and practice, they evoke the Trilateral Offices of the USPTO, the EPO, and the Japanese Patent Office, which could align their policies in view of the “common objective to harmonize the protection of industrial property rights and to contribute to an increasingly efficient worldwide patent system in the 21st century” and express hope that “…the current situation will spur this forum to restore legal certainty with respect to patenting genes and genetic diagnostic methods”. With a very large number of rare diseases having a monogenic basis, gene and gene diagnostic patent issues are pertinent to patients and researchers alike.
    Consult the PubMed abstract


    Orphanet News
    New Texts
    Spanish language emergency guidelines for antiphospholipid syndrome now available
    Spanish language emergency guidelines are now available from Orphanet for síndrome antifosfolipídico (antiphospholipid syndrome).
    New Orphanet Journal of Rare Diseases publications
    Ichthyosis Follicularis, Alopecia, and Photophobia (IFAP) syndrome
    Glucose-6-phosphatase deficiency
    Congenitally corrected transposition


    New Syndromes

    A hereditary progeroid syndrome without cardiovascular deficiencies caused by a homozygous BANF1 mutation
    The authors describe a new progeroid syndrome in two unrelated patients. This syndrome partially phenocopies Hutchinson-Gilford progeria syndrome (HGPS) but also exhibits distinctive features, including the absence of cardiovascular deficiencies characteristic of HGPS and a relatively long lifespan. A homozygous mutation in BANF1 (c.34G>A [p.Ala12Thr]) was identified by exome sequencing and functional analysis.
    Read the PubMed abstract

    Am J Hum Genet ; 650-656 ; 13 May 2011
    Chondrodysplasia and abnormal joint development associated with mutations in IMPAD1
    The authors studied three individuals from two unrelated consanguineous families with a condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and a distinctive facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, an enzyme involved in proteoglycan sulfation. A fourth unrelated patient was subsequently found to have another homozygous mutation in IMPAD1. The authors thus delineated a nosologic entity that they suggested be designated as ‘‘chondrodysplasia with joint dislocations, gPAPP type’’ or gPAPP deficiency.
    Read the PubMed abstract

    Am J Hum Genet ; 608-615 ; 13 May 2011
    Inherited neuropathies, age-related macular degeneration and hyperelastic skin linked by fibulin-5 mutations in some families
    A family with an autosomal dominantly inherited Charcot-Marie-Tooth neuropathy subtype was first studied by the authors, who found a new missense mutation in fibulin-5 (FBLN5). Screening of 112 index probands with unclassified Charcot-Marie-Tooth neuropathies detected two further fibulin-5 missense mutations in two families with Charcot-Marie-Tooth disease and hyperextensible skin. The authors also screened an additional 300 probands with exudative age-related macular degeneration. They identified two further fibulin-5 missense mutations in six patients; a mild to severe peripheral neuropathy was detected in the majority of patients with age-related macular degeneration carrying mutations in fibulin-5. This new syndrome linked to different heterozygous missense mutations in FBLN5 displays wide interindividual variability, even within families.
    Read the PubMed abstract

    Brain ; 1839-1852 ; June 2011
    FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome
    The authors present three cases with similar clinical symptoms, including Parkinsonism, supranuclear gaze palsy, visuospatial impairment and a behavioral variant of frontotemporal dementia, associated with either clinically possible or definite motor neuron disease (MND). Neuropathological examination revealed hallmarks of frontotemporal lobar degeneration with ubiquitin and TDP-43 positive neuronal inclusions (FTLD-TDP) with major involvement of subcortical and, in particular, mesencephalic structures. Two cases were sporadic, whereas the third case had a pathological variation in the progranulin gene 102delC.
    Read the PubMed abstract

    BMC Neurol ; 50 ; 10 May 2011
    Neonatal cyanosis and anaemia associated with a variant of fetal Gγ-globin gene
    The case of a “happy blue baby” is described by the authors. The infant was born cyanotic but well appearing. She had reduced haemoglobin oxygen saturation without arterial hypoxaemia, and laboratory data showed moderate anaemia with reticulosis. Her father had also had transient neonatal cyanosis. The baby initially received supplemental oxygen and erythrocyte transfusions and was discharged home at 6 days of age. By 2 months of age, her haemoglobin oxygen saturation was repeatedly higher than 95%. The authors identified a novel heterozygous γ-globin (HBG2) missense mutation in the baby and her father, and characterized this new haemoglobin, which they named Toms River.
    Read the PubMed abstract

    N Engl J Med ; 1837-1843 ; 12 May 2011

    New Genes

    Joubert syndrome and nephronophthisis: identification of mutations in TCTN2 and ATXN10, respectively
    Read the PubMed abstract
    To read more about "Joubert syndrome"
    To read more about "Nephronophthisis-associated ciliopathy"

    Cell ; 513-528 ; 13 May 2011
    Primary ciliary dyskinesia: a homozygous mutation in DNAL1 causes a disease with absent or markedly shortened outer dynein arms
    Read the PubMed abstract
    To read more about "Primary ciliary dyskinesia"

    Am J Hum Genet ; 599-607 ; 13 May 2011
    X-linked nonsyndromic sensorineural deafness type DFN: 4 mutations in SMPX identified
    Read the PubMed abstract
    To read more about "X-linked nonsyndromic sensorineural deafness type DFN"

    Am J Hum Genet ; 621-7; 628-34 ; 13 May 2011
    Autosomal-dominant retinitis pigmentosa: a missense mutation in PRPF6 is responsible for some cases
    Read the PubMed abstract
    To read more about "Retinitis pigmentosa"

    Am J Hum Genet ; 643-649 ; 13 May 2011
    Infantile mitochondrial cardiomyopathy: mitochondrial alanyl-tRNA synthetase mutations identified
    Read the PubMed abstract
    To read more about "Fatal infantile cytochrome C oxidase deficiency"

    Am J Hum Genet ; 635-642 ; 13 May 2011
    Amelogenesis imperfecta and gingival hyperplasia syndrome: a homozygous nonsense mutation in FAM20A at cause
    Read the PubMed abstract
    To read more about "Gingival fibromatosis - dental abnormalities"

    Am J Hum Genet ; 616-620 ; 13 May 2011
    Autosomal dominant Adams-Oliver syndrome: a gain-of-function mutation of ARHGAP31 identified
    Read the PubMed abstract
    To read more about "Adams-Oliver syndrome"

    Am J Hum Genet ; 574-585 ; 13 May 2011
    Kufs disease type A: mutations in CLN6 are responsible
    Read the PubMed abstract
    To read more about "CLN4A disease"

    Am J Hum Genet ; 566-573 ; 13 May 2011
    Microlissencephaly: identification of NDE1 mutations in two families
    Read the PubMed abstract
    To read more about "Lissencephaly syndrome, Norman-Roberts type"

    Am J Hum Genet ; 536-547 ; 13 May 2011
    Progressive myoclonus epilepsy type 1: a mutation in GOSR2 at cause in a form with early-onset ataxia
    Read the PubMed abstract
    To read more about "Unverricht-Lundborg disease"

    Am J Hum Genet ; 657-663 ; 13 May 2011
    Pontocerebellar hypoplasia type 5: the disease results of compound heterozygosity for TSEN54 mutations
    Read the PubMed abstract
    To read more about "Pontocerebellar hypoplasia type 5"

    Eur J Hum Genet ; 724-726 ; June 2011
    Familial progressive hyper- and hypo-pigmentation: some families have KITLG mutations
    Read the PubMed abstract
    J Invest Dermatol ; 1234-1239 ; June 2011

    Research in Action

    Gene-based networks for orphan diseases are useful but have limitations
    In order to identify and investigate rare disease relationships based on shared genes or shared functional features, the authors of an interesting new study published in the American Journal of Human Genetics conducted a bioinformatic-based global analysis of all orphan diseases (OD) with known disease-causing mutant genes. Starting with a bipartite network of known OD and OD-causing mutant genes and using the human protein interactome, the authors constructed and topologically analysed three networks: the orphan disease network, the orphan disease-causing mutant gene network, and the orphan disease-causing mutant gene interactome. The results of this effort show that a majority of orphan disease-causing mutant genes are essential, in contrast to common disease-causing mutant genes, which are predominantly nonessential. The authors report that “… OD-causing mutant genes are topologically important in the protein interactome and are ubiquitously expressed. Additionally, functional enrichment analysis of those genes in which mutations cause ODs shows that a majority result in premature death or are lethal in the orthologous mouse gene knockout models” . Going further, to address the limitations of traditional gene-based disease networks, the authors constructed and analysed OD networks on the basis of shared enriched features such as biological processes, cellular components, pathways, phenotypes, and literature citations. They identified several additional OD-OD relations from analyzing these functionally-linked OD networks, which “are both phenotypically similar and phenotypically diverse”. The authors report that “the wiring of the gene-based and other feature-based OD networks are largely different … [suggesting] that the relationship between ODs cannot be fully captured by the gene-based network alone”.
    Consult the PubMed abstract

    Clinical Research
    Idiopathic pulmonary fibrosis: pirfenidone has a favourable benefit risk profile and represents an appropriate treatment option
    Read the PubMed abstract
    To read more about "Idiopathic pulmonary fibrosis"

    Lancet ; 1760-1769 ; 21 May 2011
    Sickle cell anaemia: hydroxycarbamide can be considered for very young children
    Read the PubMed abstract
    To read more about "Sickle cell anemia"

    Lancet ; 1663-1672 ; 14 May 2011
    Metastatic pancreatic cancer: FOLFIRINOX is an option for the treatment of patients with good performance status
    Read the PubMed abstract
    To read more about "Pancreatic carcinoma"

    N Engl J Med ; 1817-1825 ; 12 May 2011
    Hereditary angioedema: an integrated analysis confirms effectiveness and tolerability of ecallantide in acute attacks
    Read the PubMed abstract
    To read more about "Hereditary angioedema"

    J Allergy Clin Immunol ; Epub ahead of print ; 8 April 2011
    Portal vein thrombosis: radiological classification and natural history of portal cholangiopathy
    Read the PubMed abstract
    To read more about "Portal vein thrombosis"

    Gut ; 853-860 ; June 2011
    Juvenile dermatomyositis: a study found a strong familial aggregation of specific autoimmune diseases
    Read the PubMed abstract
    To read more about "Juvenile dermatomyositis"

    Pediatrics ; e1239-e1246 ; May 2011
    Gene Therapy
    Hemophilia B: a new AAV vector allowed long-term and safe expression of human factor IX in macaques
    The authors designed a new self-complementary adeno-associated virus (AAV) vector encoding a codon optimized human factor IX (hFIX) gene pseudotyped with serotype 5 and 8 capsid proteins. Single intravenous administration of different doses of this vector was tested in 24 macaques. Macaques transduced with 2 x 1011 vp/kg were followed for the longest period (around 5 years), during which time expression of hFIX remained >10% of normal level. All macaques developed serotype-specific antibodies but no capsid-specific cytotoxic T lymphocytes were detected. The liver was preferentially transduced with 300-fold more proviral copies than extrahepatic tissues. Long-term biochemical, ultrasound imaging, and histologic follow-up of this large cohort revealed no toxicity.
    Read the PubMed abstract

    To read more about "Hemophilia B"

    Mol Ther ; 876-885 ; May 2011
    Therapeutic Approaches
    Congenital diaphragmatic hernia: antenatal sildenafil treatment attenuates pulmonary hypertension in a rat model
    The authors used a rat model of congenital diaphragmatic hernia (CDH). They administered sildenafil to pregnant rat from embryonic day 11.5 to embryonic day 20.5. The drug crossed the placenta, improved lung structure, increased pulmonary vessel density, reduced right ventricular hypertrophy, and improved postnatal nitric oxide-induced pulmonary artery relaxation. No sildenafil adverse effect was detected.
    Read the PubMed abstract

    To read more about "Congenital diaphragmatic hernia"

    Circulation ; 2120-2131 ; 17 May 2011
    Loeys-Dietz syndrome: dexamethasone normalizes aberrant elastic fiber production and collagen I secretion in fibroblasts
    The authors analysed the fibroblasts from 12 Loeys-Dietz syndrome (LDS) patients. All LDS fibroblasts with TGFβ-R1 mutations demonstrated decreased expression of elastin and fibulin 1 genes and impaired deposition of elastic fibers. In contrast, fibroblasts with TGFβ-R2 mutations consistently demonstrated intracellular accumulation of collagen type I. Treatment of the cell cultures with dexamethasone normalized elastic fiber production in fibroblasts with TGFβ-R1 mutations and also corrected the abnormal secretion of collagen type I from fibroblasts with TGFβ-R2 mutations. As the organogenesis-relevant elastic fiber production occurs exclusively in late fetal and early neonatal life, these findings may have implications for treatment in early life.
    Read the PubMed abstract

    To read more about "Aortic aneurysm syndrome, Loeys-Dietz type"

    Eur J Hum Genet ; 624-633 ; June 2011
    Cushing disease: targeting zebrafish and murine pituitary corticotroph tumours with a CDK inhibitor
    In order to rapidly identify small molecule cyclin-dependant kinase (CDK) inhibitors with optimal potency for Cushing disease, the authors generated a new model. Their transgenic zebrafish recapitulated early features of corticotroph adenomas and adult fish developed hypercortisolaemia-induced metabolic disturbances. A pharmacologic CDK2/cyclin E inhibitor, R-roscovitine, which specifically reversed corticotroph expansion in live fish embryos, was identified. The authors further validated that orally administered R-roscovitine suppressed adrenocorticotropin (ACTH) and corticosterone levels, and also restrained tumour growth in a mouse model of ACTH-secreting pituitary adenomas.
    Read the PubMed abstract

    To read more about "Cushing disease"

    PNAS ; 8414-8419 ; 17 May 2011

    Patient Management and Therapy

    Myotonic dystrophy type 2 and related disorders: workshop produces guidelines for diagnosis and management
    The 180th international European Neuro Muscular Centre (ENMC) workshop assembled experts from Europe and the USA to discuss myotonic dystrophy,a rare disorder characterised by autosomal dominant progressive myopathy, myotonia and multiorgan involvement and for which two distinct entities are currently known: Myotonic dystrophy type 1 (DM1, Steinert disease), and Myotonic dystrophy type 2 (DM2). This workshop concentrated principally on DM2, reviewing the spectrum of clinical expression, guidelines for molecular testing, and aspects of patient management. An open-access online report of this workshop is now available from Neuromuscular Disorders , the official journal of the World Muscle Society.
    Consult the report

    von Hippel-Lindau disease: a clinical and scientific review
    The authors present a review on clinical and genetic features of von Hippel-Lindau disease, with a brief review on molecular pathogenesis and an outline on management and tumour surveillance strategies.
    Read the PubMed abstract

    To read more about "Von Hippel-Lindau disease"

    Eur J Hum Genet ; 617-623 ; June 2011
    Achalasia: a review on management with results of a large trial comparing surgery and pneumatic dilation
    Two different studies on achalasia have been published recently. The first is mainly dedicated to achalasia treatment. The most successful therapies, pneumatic dilation and surgical myotomy, are reviewed and compared, taking into account the results of the second paper. The latter reports on a five country randomised trial which included 201 patients with newly diagnosed achalasia. After 2 years of follow-up, laparoscopic Heller’s myotomy and pneumatic dilation had comparable success. The first paper also reviews pharmacological treatments and suggests an algorithm for the treatment of achalasia.
    Read the PubMed abstract

    To read more about "Primary achalasia"

    Gut ; 869-876 ; June 2011
    N Engl J Med ; 1807-1816 ; 12 May 2011
    Gastric MALT lymphoma: EGILS consensus report
    This consensus report of the EGILS (European Gastro-Intestinal Lymphoma Study) group includes recommendations on the management of gastric extranodal marginal zone B-cell lymphoma of MALT (mucosa-associated lymphoid tissue). They are based on data from the literature and on intensive discussions and votings of the experts during their annual meetings.
    Read the PubMed abstract

    To read more about "MALT lymphoma"

    Gut ; 747-758 ; June 2011
    Fragile X syndrome: an American Academy of Pediatrics guidance
    The Committee on Genetics of the American Academy of Pediatrics issued a guidance for management of children with fragile X syndrome. The report summarizes issues regarding clinical diagnosis, laboratory diagnosis, genetic counseling, related health problems, behaviour management, and age-related health supervision guidelines.
    Read the PubMed abstract

    To read more about "Fragile X syndrome"

    Pediatrics ; 994-1006 ; May 2011
    Pierre-Robin sequence: from diagnosis to development of an effective management plan
    The authors conducted an exploration of the pathogenesis, developmental and genetic models, morphology, and syndromes and malformations associated with Pierre-Robin sequence (PRS). Current classification systems for PRS do not account for the heterogeneity among infants with PRS, which impairs optimal individual management. Although upper airway obstruction for some infants with PRS can be treated adequately with positioning, other children may require a tracheostomy. Health care providers must understand the anatomy and mechanism of airway obstruction to develop an individualized treatment plan to improve breathing and achieve optimal growth and development. The article provides a comprehensive overview of evaluation strategies and therapeutic options for children born with PRS.
    Read the PubMed abstract

    To read more about "Isolated Pierre Robin syndrome"

    Pediatrics ; 936-948 ; May 2011
    Parents’ and children’s communication about genetic risk: a qualitative study, learning from families’ experiences
    The authors explored how genetic risk information is shared between family members and the factors affecting it, to inform future service development and provision. A volunteer group of parents, children (8-11 years) and young people (12+ years) in families affected by or at risk of one of six inherited genetic conditions (cystic fibrosis, neurofibromatosis, Duchenne muscular dystrophy, haemoglobinopathies, familial adenomatous polyposis, and Huntington disease) was interviewed. A total of 33 families participated, which included 79 individuals. Parents often found discussing genetic risk information very difficult and emotionally painful. Children usually preferred to learn about the genetic condition gradually throughout childhood. Many parents thought health professionals should provide more advice to assist them in providing developmentally appropriate information.
    Read the PubMed abstract

    Eur J Hum Genet ; 640-646 ; June 2011
    Primary angiitis of the central nervous system: a review
    Although primary angiitis of the CNS (PACNS) remains poorly understood, meaningful progress in the understanding and clinical approach to PACNS has been made in the past three decades. The authors present a review on diagnostic criteria and clinical features in adults and children. They also reviewed literature on PACNS treatment, but no randomised trials have been carried out. However, case series in adults suggest good outcomes can be obtained when patients are treated with glucocorticoids or glucocorticoids and cyclophosphamide.
    Read the PubMed abstract

    To read more about "Primary angiitis of the central nervous system"

    Lancet Neurol ; 561-572 ; June 2011
    Mucopolysaccharidosis: diagnosis and management of ophthalmological features
    In patients with mucopolysaccharidosis (MPS), typical ocular features include corneal clouding, ocular hypertension/glaucoma, retinal degeneration and optic nerve atrophy. As an early intervention, haematopoietic stem cell transplantation and/or enzyme replacement therapy are likely to improve visual outcome. To the authors, it is of fundamental value to increase awareness and knowledge among ophthalmologists of the ocular problems affecting MPS patients and to highlight potential diagnostic pitfalls and difficulties in patient care. This review provides insight into the prevalence and severity of ocular features in patients with MPS and gives guidance for early diagnosis and follow-up of MPS patients.
    Read the PubMed abstract

    To read more about "Mucopolysaccharidosis"

    Br J Ophthalmol ; 613-619 ; May 2011
    Three new Clinical Utility Gene Cards available
    EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases. The European Journal of Human Genetics has published three new Clinical Utility Gene Cards for:
    Blue cone monochromatism
    Malignant hyperthermia


    Orphan Drugs
    Applying innovative trial designs to rare disease studies
    An article published in the Journal of Clinical Epidemiology suggests that innovative clinical studies may accommodate rare disease trials that do not readily lend themselves to more conventional designs. By searching the literature for examples of uncommon designs applied to rare diseases, the authors “… found few examples of rare disease studies using these techniques, perhaps reflecting both methodological concerns and a lack of awareness among researchers”. Presenting the merits and shortcomings of several approaches identifying and offering a “practical framework to help researchers in selecting between design choices” the authors evoke the crossover design; n-of-1 trials; and adaptive designs such as a response-adaptive randomisation design; a ranking and selection design; an internal pilot design; or a sequential design. Some of these approaches could be used in combination. In selecting a particular design, the authors counsel that the choice “should be guided by factors related to the intervention, disease, anticipated recruitment duration and success, and current state of knowledge about the treatment”.

    The authors identify several methodological challenges to be resolved in order to use unconventional studies for rare disease medicinal products. These include clarifying limitations, validity, and applicability of particular approaches. Furthermore, established statistical methods and software packages for uncommon approaches may not be widely available. Finally, the authors acknowledge that the “complexity of these designs may also make it difficult for researchers to acquire truly informed consent from prospective participants” and that “novel methods may also be unfamiliar to regulatory authorities and peer reviewers. As such, researchers may face barriers in explaining methods and arguing for different interpretive standards than those conventionally applied” .
    Consult the PubMed abstract

    A comparison of orphan and non-orphan cancer drug clinical trials
    A study appearing in JAMA, Journal of the American Medical Association, compares the characteristics of cancer orphan drug pivotal clinical studies with similar non-orphan drug trials. After identifying all new orphan and non-orphan drugs approved in the USA between 2004 and 2010 to treat cancer, the authors gathered data on key development variables. Assessing and comparing various elements (regulatory characteristics, indications, trial design features, adverse safety outcomes) for 15 orphan and 12 non-orphan cancer products, they found that orphan drug trials involved smaller numbers of participants, were less likely to be randomised, less likely to be double-blind, and more likely to assess disease response (versus overall survival). Furthermore, more patients had adverse effects in the orphan drug trials.
    Consult the PubMed abstract

    Promiscuity as a virtue… when old drugs learn new tricks
    The authors of a new study published in Pharmaceutical Research outline the identification of 34 studies in the literature that describe screening various libraries of FDA-approved drugs against whole cell or target assays. Each of these studies was able to identify at least one compound with a suggested new bioactivity not previously described. The authors demonstrate that “thirteen of these drugs were active against more than one additional disease, thereby suggesting a degree of promiscuity”. Next, the authors looked at how to avoid the repetition of discoveries already made (duplication of effort) and show that 109 molecules were identified by screening in vitro. Of these, the “…molecules appear to be statistically more hydrophobic with a higher molecular weight and AlogP than orphan designated products with at least one marketing approval for a common disease indication or one marketing approval for a rare disease from the FDA’s rare disease research database. … Capturing these in vitro data on old drugs for new uses will be important for potential reuse and analysis by others to repurpose or reposition these or other existing drugs”. The authors evoke the NIH Genomics Center database described as a “comprehensive resource of clinically approved drugs to enable repurposing and chemical genomics” to be used along with the NCGC screening resources as a component of the NIH therapeutics for rare and neglected diseases (TRND) programme and call for “an exhaustive database that cross references the molecules, papers, and activities” which would be a “… valuable starting point ... and capturing the hit rates of such libraries versus other compound library screening, preclinical and clinical data would be valuable”.
    Consult the Pubmed abstract



    Funding opportunities for Friedreich ataxia research
    Friedreich ataxia is characterised by difficulties coordinating movements, associated with neurological signs (dysarthria, loss of reflexes, decrease of deep sensation, pes cavus and scoliosis), cardiomyopathy and sometimes diabetes mellitus. The Friedreich's Ataxia Research Alliance (FARA) is a non-profit organisation dedicated to curing Friedreich ataxia (FA) through research. FARA will support research with grants provided by the organisation itself and in collaboration with partner organisations dedicated to advancing FA research and treatments. The following awards are currently open:

    2011 Keith Michael Andrus Memorial Award
    The Keith Michael Andrus Memorial Award is specifically designated for cardiac research and will be awarded to a grant proposal that features key contributions toward understanding and/or treating the cardiac complications associated with FA. Proposals for basic, translational, and clinical research will be considered. The total award is limited to $75,000 (direct costs only). Application/Proposal due date: 1 September 2011

    New Investigator Award
    New Investigator Grants Proposals are accepted twice a year (1 March and 1 September) from new scientists in the FA research community. This award is to support young investigators who are beginning their independent research careers and have a strong interest in pursuing research that advances knowledge and insights of FA. This award is also intended to support investigators from related fields of research who want to apply their knowledge and experience to a specific area of FA research. Proposals for basic, translational and clinical research will be considered.
    For details and application


    News from the Patients' Associations
    Tireless commitment: how patient advocacy is forwarding translational research for Diamond Blackfan anaemia
    A beautifully rendered narrative appearing in the journal Seminars in Hematology demonstrates “patient power” at its finest. The Daniella Maria Arturi Foundation has made a significant contribution to the facilitation of translational research for Diamond Blackfan anaemia, a congenital aregenerative and often macrocytic anaemia with erythroblastopenia, typically presenting within the first two years of life. The author, mother of two affected children and creator, with her husband, of the foundation, acknowledges the “the tireless commitment of noble and supportive participants to advance the cause. It is through this mutual support and friendship that a little bit of magic occurs”. The “magic” of advancing science requires continuous and sustained effort, however. As the author writes, “I liken it to plate spinning: you must keep all the plates going simultaneously to be successful. There is the fundraising plate, the communications plate, the medical conference plate, the clinical and scientific plate, the federal advocacy plate, the Foundation-as-a-business plate, and, and, and”. The article leaves the reader reflecting on where rare disease research, prevention, diagnostics, treatment and support would be today without the “tremendous dynamics” the patient advocacy group is able to create.
    Consult the PubMed abstract


    Courses & Educational Initiatives

    2nd Course in Eye Genetics-EuroMediterranean University Center of Bologna
    Eye Genetics is a 4-day long postgraduate level course addressed to both researchers and clinicians seeking an up-to-date introduction to the field of ophthalmogenetics today. It provides an overview of the clinical developments of modern genetics in different fields of ophthalmology. The topics covered in the course are: hereditary retinal diseases, genetics of retinitis pigmentosa, genetics of age related macular degeneration, genetics of myopia, genetics of glaucoma, genetics of corneal pathology, genetics of optic nerve diseases, gene therapy.
    For further details

    Goldrain Courses in Clinical Cytogenetics and in Prenatal Genetic Diagnosis
    The upcoming Goldrain Clinical Cytogenetics course, from 28 August to 3 September 2011 at the Goldrain Castle in South Tyrol (Italy), focuses on phenotypic findings, mechanisms of origin and transmission and correlations of clinical patterns with the chromosomal imbalance. Special attention is paid to an understanding how deletions and/or duplications of chromosomal segments cause developmental defects. The course also addresses the optimal application of the diagnostic possibilities including molecular cytogenetic methods for a precise determination of segmental aneuploidy.
    The Prenatal Genetic Diagnosis course, taking place from 15 to 21 October 2011 also at the Goldrain Castle, is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination. TOPICS include Techniques: Amniocentesis and amniocyte examination, chorionic villus sampling and examination, cordocentesis and fetal blood examination, pre-implantation genetic diagnosis, prenatal diagnosis from fetal DNA and cells in maternal blood, QF-PCR and MLPA, DNA-arrays, aneuploidy screening and PGD, QF-PCR as a stand-alone test. Obstetric issues: Obstetric indications for PD, prenatal dysmorphology and assessment of congenital developmental defects, PD in twins and selective fetocide, the fetal heart as a window to detect genetic problems, risk assessment for chromosomal anomalies following non-invasive prenatal testing, prenatal ultrasonic diagnosis: routine screening approach; specific examinations; fetal therapy; prenatal magnetic resonance examination. Genetic issues: genetic counseling in the context of potential prenatal diagnosis, genetic indications for PD, estimation and calculation of recurrence risks, techniques and their indications: conventional cytogenetics; molecular cytogenetics; mutation analysis; biochemical diagnosis; questionable results; mosaicism and chimaerism. Ethical considerations.
    For further details

    4th International Postgraduate Course on Lysosomal Storage Disorders: Diagnostic Background and Clinical Therapy
    The University of Rostock is organising the 4th International Postgraduate Course on Lysosomal storage disorders: diagnostic background and clinical therapy to take place in Berlin, Germany from 14-15 November 2011. Scientific excellence in talks will be connected with presentations and discussion of real clinical cases embedded into a communicative and inspiring atmosphere.
    For further details

    Master of Science in Haemoglobinopathy
    A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy – such as counsellors, clinical psychologists, nurse specialists and midwives.
    For further details

    Orphan Academy 2011 programme
    The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
    For further details

    EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
    The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
    For further details


    What's on Where?

    9th East European Scientific-Training Conference: Rare Diseases - Diagnosis, Treatment and Patent Care
    Date: 15-17 July 2011
    Venue: Cedzyna, Poland

    Outstanding scientists in the field of mucopolysaccharidosis and other rare diseases, health professionals treating with enzyme replacement therapies, leaders of patient organisations in the country and abroad and representatives of government will participate in this event.
    For further details

    VI Cornelia de Lange Syndrome World Conference
    Date: 27-31 July 2011
    Venue: Copenhagen, Denmark

    Offering a professional symposium during which the latest developments in research, care and treatment will be discussed, as well as a family conference.
    For further details

    Society for the Study of Inborn Errors of Metabolism - Annual Symposium 2011
    Date: 30 August - 02 September 2011
    Venue: Geneva, Switzerland

    The main scientific programme includes a joint session with the International Society for Newborn Screening (ISNS), a session on adult metabolic diseases, creatine metabolism and related disorders, gene therapy, plenary and free communications sessions, and much more.
    For further details

    European Conference on Post Polio Syndrome
    Date: 31 August - 02 September 2011
    Venue: Copenhagen, Denmark

    This international conference is being held by the European Polio Union, and The Danish Society of Polio and Accident Victims.
    For further details

    15th International Workshop on Fragile X and Early-Onset Cognitive Disorders
    Date: 4-7 September 2011
    Venue: Berlin, Germany

    Topics include: Everything you always wanted to know about Fra(X); Novel causes of X-linked intellectual disability (XLID); Autosomal dominant and recessive forms of ID; ID syndromes: clinical, neurological and neuro-anatomical findings; Functional studies, animal models, emerging pathways; Population-specific and epidemiological aspects; Diagnosis, carrier detection and therapy; Molecular links between cognitive and behavioural disorders; Genetic determinants of intelligence, and much more.
    For further details

    3rd International Symposium on Pheochromocytoma and Paraganglioma
    Date: 14-17 September 2011
    Venue: Paris, France

    An opportunity to learn the state-of-the-art in pheochromocytoma and paraganglioma, to meet the leading experts in the field (coming from Europe, United States of America, Asia and Australia), to exchange and discuss the most recent research data as well as to develop international collaborative studies between clinical and/or academic research teams. This symposium takes place during a unique moment when key pathophysiological mechanisms and new therapeutic targets have been discovered and translated from bench to bedside.
    For further details

    18th Pediatric Rheumatology European Society Congress (PRES2011)
    Date: 14-18 September 2011
    Venue: Bruges, Belgium

    Offering a venue for continued education, the sharing of new research developments, and fostering academic collaboration, for clinicians, trainees, scientists and allied health professionals in the field of paediatric rheumatology. The scope of PRES2011 includes genetics, etiopathogenesis, clinical innovations and recent advances in treatment covering a wide spectrum of both common and rare rheumatic diseases in children.
    For further details

    13th International Conference on Chronic Myeloid Leukemia: Biology and Therapy
    Date: 22-25 September 2011
    Venue: Estoril, Portugal

    Speakers will present the newest and often unpublished data relating to 1) the biology of CML including the origin of BCR-ABL1, signal transduction, basis of disease progression, action of tyrosine kinase inhibitors and mechanisms underlying resistance to TKI; and 2) aspects of treatment including prediction and definition of responses, drugs used in combination, molecular monitoring, targeting residual stem cells and approaches to a cure.
    For further details

    EurokeratoConus II: 2nd European Congress on Keratoconus
    Date: 23-24 September 2011
    Venue: Bordeaux, France

    Sessions will address: Epidemiology and Pathogenesis; Corneal Biomechanics; New treatments and much more.
    For further details

    5th International Conference on Birth Defects and Disabilities in the Developing World
    Date: 24-27 September 2011
    Venue: Lodz, Poland

    The primary theme of the conference will be economics of healthcare and methods for establishing sustainable financial resources to implement programs of value to health and assure access to care. Other topics include integration of services into national primary health programs for care of neonates and children with birth defects and disabilities; monitoring risk factors for major defects globally; preconception care; and development of networks and partnerships for most efficient utilization of the limited resources.
    For further details

    Pharmaceutical Pricing and Reimbursement Information Conference 2011
    Date: 29-30 September 2011
    Venue: Vienna, Austria

    The WHO Collaborating Centre for Pharmaceutical Pricing and Reimbursement Policies in Vienna invites participants to discuss pharmaceutical policies and their practical implementation in the light of current challenges such as the economic crisis with high ranking experts and policy makers. The main topics of the conference are pricing and reimbursement of medicines in the in- and out-patient sector, interface management and the rational use of medicines from a comprehensive, international and European perspective. Orphan Drugs will be subject to several discussions.
    For further details

    12th International Congress of Human Genetics
    Date: 11-15 October 2011
    Venue: Montreal, Canada

    The Congress includes invited presentations from leading international geneticists, a variety of symposia, workshops, posters and other sessions focusing on the most important and recent developments in human genetics, including: basic and molecular genetics; genomics; epigenetics; clinical genetics; population genetics; genetic counselling; ethics; education; cancer genetics; prenatal genetics; and public health genetics.
    For further details

    European Congress on Myocardial and Pericardial Diseases
    Date: 13- 15 October 2011
    Venue: Lisbon, Portugal

    Focusing on the key contemporary issues in myocardial and pericardial diseases, the meeting includes the current state of the art management of myocardial dysfunction, aetiology and pathogenesis of inherited cardiac disease, and the role of current and merging multimodality imaging.
    For further details

    Tuberous Sclerosis Complex Scientific Day
    Date: 14 October 2011
    Venue: Paris, France

    This meeting will be an opportunity for doctors and researchers to meet, to advance common projects in order to improve care of TSC patients. Participants desiring to present their work will be offered an opportunity to do so during a specific session in the end of the day.
    For further details

    27th Annual Meeting of the Histiocyte Society
    Date: 17-19 October 2011
    Venue: Vienna, Austria

    The programme features a presentation on recent publications on Erdheim-Chester disease that have provided important new insights into the pathogenesis, classification and management of this challenging histiocytic disorder. Other sessions include LCH in adults, including a review of lessons learned from the Society’s first adult LCH trial, LCH-A1, as well as other treatment experiences, through which a consensus approach to the treatment of LCH in the adult population will be developed This year’s meeting will also focus on the Society’s soon-to-be-launched International Rare Histiocytic Disorders Registry and the opening of the LCH-IV study.
    For further details

    Rare 2011: The Eurobiomed Meetings on Rare Diseases
    Date: 2-4 November 2011
    Venue: Montpelier, France

    This French-language event features an English-language “European Day” co-hosted by Eurobiomed and the European Union Committee of Experts on Rare Diseases (EUCERD) that will explore shared data to improve healthcare management for rare diseases.
    For further details

    Treat-NMD Global Conference
    Date: 8-11 November 2011
    Venue: Geneva, Switzerland

    The conference will comprise a range of sessions addressing the challenges in the neuromuscular field, including: Delivery of future therapies; Biomarkers; Care considerations; Neuromuscular diseases and society; and Regulatory issues, orphan drugs and the rare disease field.
    For further details

    Sanfilippo Foundation Switzerland International Congress
    Date: 8-10 December 2011
    Venue: Geneva, Switzerland

    Research toward a treatment is the theme of this conference focusing on innovative research to treat mucopolysaccharidosis.
    For further details

    International Congress on Research of Rare and Orphan Diseases
    Date: 29 February - 2 March 2012
    Venue: Basel, Switzerland

    The Swiss-based Blackswan Foundation and Gebert Ruf Stiftung Foundation, both active in supporting research activities in Rare Diseases, are preparing an international congress of which the main topics will include Gene and cell therapy; Stem cells; Diagnostics; Therapeutic applications; and Genomic disorders. The congress will be open to scientific researchers, specialized scholars, professionals and officials.
    For further details

    Second ASID Congress of the African Society for Immunodeficiencies
    Date: 8-11 March 2012
    Venue: Hammamet, Tunisia

    This second congress, postponed from its original 2011 date, will be an excellent opportunity to strengthen the capacity of colleagues all over the continent to better diagnose and manage patients with PIDs. The commitment and contribution of international experts, societies and associations to this process is highly appreciated.
    For further details

    Fourth International Meeting on Primary Central Hypoventilation Syndromes
    Date: 13-14 April 2012
    Venue: Warsaw, Poland

    The fourth international CHS meeting will be organized by the European CHS Consortium and will address physicians, researchers, families and all persons involved or interested in Central Hypoventilation Diseases.
    For further details


    Press & Publications

    A definitive volume on craniosynostosis published
    Craniosynostosis – the premature fusion of the cranial sutures of an infant’s skull – is a challenging and complex condition that can occur as part of a syndrome or in isolation. In the last two decades, increased knowledge about the structure and function of the human genome has enabled the discovery of the molecular aetiologies of most forms of syndromic craniosynostosis, which in turn has allowed for the analysis of normal and abnormal sutural biology from the atomic to the population-based level. In parallel with the increase in basic biological understanding, advances in clinical diagnosis and treatment have been achieved including improved prenatal imaging technology and craniofacial surgical techniques as well as condition-specific care in specialised hospitals and clinical units. Craniosynostoses: Molecular Genetics, Principles of Diagnosis, and Treatment offers a comprehensive overview on the subject. With contributions from the foremost authorities in the field, topics include a historical review, basic biological and molecular studies, the various common and uncommon syndromes, nonsyndromic craniosynostoses, genetic testing, prenatal ultrasonography, and recent methods of neurosurgical and maxillofacial treatment.
    Title: Craniosynostoses: Molecular Genetics, Principles of Diagnosis, and Treatment
    Authors: M Muenke, W Kress, H Collmann, BD Solomon – Eds.
    Publisher: Karger, 2011
    ISBN: 978-3-8055-9594-0

    Corneal dystrophies: An in-depth look at recent achievements and forthcoming challenges
    Corneal dystrophies (CD) are bilateral hereditary disorders of the cornea in which one or several parts of the cornea lose their transparency. As the dystrophy can start in different layers of the cornea, they are classified accordingly as epithelial dystrophies, stromal dystrophies and endothelial dystrophies. Corneal Dystrophies is a new book that includes a description of the new international ICD classification of CD reflecting what is currently known of the clinical, pathological, and genetic aspects of these disorders. Further contributions give an insight into differential diagnostics and histology, as well as DNA analysis of CD providing additional information about the pathogenesis. Procedures such as the phototherapeutic keratectomy with the excimer laser, the new modalities of lamellar keratoplasty, and penetrating keratoplasty are also described.
    Title: Corneal Dystrophies
    Authors: W Lisch, B Seitz –Eds.
    Publisher: Karger, 2011
    ISBN: 978-3-8055-9720-3

    Updated commercially available report details the orphan drug market in Europe

    The 2011 edition of Orphan Drugs in Europe: Pricing, Reimbursement, Funding & Market Access is a fully revised and expanded version of the best-selling 2008 report commercially available from justpharma reports. Bringing together often hard-to-obtain information from across Europe, highlights of this overview of the orphan drug market in Europe include:
    Availability, price and reimbursement status for all 60 EU-designated orphan drugs with centralised marketing authorisations up to end-2010
    How orphan drug policies differ across Europe. Expanded sections on each EU-5 country. Situation in 20 countries described in total
    Key role of special ‘high cost’ funding systems explained
    Impact of health technology assessment
    The myths and realities of orphan drug costs
    How risk sharing schemes and patient registries can help bridge the data gap
    Ways to provide pre-approval early access
    12 case studies
    The potential for EU collaboration on clinical added value of orphan drugs
    Learn more

    New children’s book can help parents explain their own rare disease

    Where Did Mommy’s Superpowers Go? is a warm-hearted story useful to any parent struggling to balance a serious health crisis while caring for small children. Told from the child’s point of view, the story shows that what adults tell children about a family member’s critical illness may not be nearly as important as how adults share this information. What makes this book special is that no particular disease or treatment is specified, so it can be a useful resource for all families facing this challenge. Written by Jenifer Gershman, a mother who struggled with rare disease amyloidosis, Where Did Mommy’s Superpowers Go? can help children better understand and accept the illness of a parent, and also help parents to talk to their children about their disease.
    Title: Where Did Mommy’s Superpowers Go?
    Author: Jenifer Gershman
    Publisher: Sweet Dreams Publishing, 2011
    ISBN-13: 978-0982446195
    Learn more


    Orphanews Europe, the newsletter of the European Union Committee of Experts on Rare Diseases
    Orphanews Europe is supported by the European Commission's DG SANCO
    and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Ségolčne Aymé
    Editor: Louise Taylor
    Contact Us
    Editorial Board: Ségolčne Aymé, Kate Bushby, Catherine Berens, Helena Kaariainen, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Christophe Roeland

    EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Radka Tincheva (Bulgaria), Ivo Baric (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek Jr. (Czech Republic), Marianne Jespersen (Denmark), Inna Vabamae (Estonia), Helena Kaariainen (Finland), Alain Garcia (France), Birgit Schnieders (Germany), Christos Katamis (Greece), Janos Sandor (Hungary), Sveinn Magnusson (Iceland), John Devlin (Ireland), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Jonas Bartlingas (Lithuania), Yolande Wagener (Luxembourg), Maria-Louise Borg (Malta), Harry Seeverens (Netherlands), Stein Are Aksnes (Norway), Jakub Adamski (Poland), Luis Nunes (Portugal), Ana Maria Vladareanu (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Isabel Pena-Rey (Spain), Michael Soop (Sweden), Sabina Gallati (Switzerland), Edmund Jessop (UK)
    EUCERD ECDC Representative: Andrew Amato
    EUCERD Patient Organisation Representatives: Dorica Dan, Torben Gronnebaek, Yann Le Cam, Christel Nourissier
    EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
    EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolčne Aymé, Jean Donadieu, Dian Donnai, Laura Fregonese, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
    EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Sophie Koutouzov, Gerard Wagemaker
    EUCERD European Commission Participants: Catherine Berens, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Antoni Montserrat Moliner, Christophe Roeland, Stefan Schreck, Kerstin Westermark (EMA-COMP)
    Orphanet Partner Country Representatives: Tamara F. Sarkisian (Armenia), Yvonne Zurynski (Australia), Till Voigtlander (Austria), Herwig Jansen (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann-Spangenberg (Germany), Michael Petersen (Greece), Sandor Janos (Hungary), Andrew Green (Ireland) Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbane (Lebanon), Viadutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequieros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Desirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
    For more information on the European Union Committee of Experts on Rare Diseases
    Orphanet - All rights reserved