23 June 2010 print
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A good thing comes to an end…
but leaves behind a defined network of dysmorphology experts, an online diagnostic tool and guidelines for four rare diseases

English scribe Geoffrey Chaucer long ago observed that all good things must end. But so soon? The Dyscerne Network launched in early June 2007 with three years of DG Sanco funding to improve the diagnostics, management, and dissemination of information for rare dysmorphic syndromes. The rationale behind the project was clear:

“Individually, most of the 2,500 recognised dysmorphic conditions are rare, but collectively they cause high morbidity, so it is important that patients are diagnosed correctly and promptly, and receive appropriate care. An experienced clinical dysmorphologist can recognize and diagnose conditions based on these features; however there are relatively few experts in clinical dysmorphology, and access to one of these specialists varies widely across the EU.”

An initial goal thus identified centres of expertise for rare dysmorphologic disorders and created a network amongst those centres. Such a network could “capture complementary expertise, improve standards in diagnosis and management, facilitate patients’ access to rare disease services, and act as a model for other networks of expertise.” Over 80 dysmorphology experts from 31 European countries were invited to join the Network - either as members of an expert review panel or serving as contact points through which undiagnosed cases could be submitted. Other functions of the network include contributing to the definition of newly-identified dysmorphic conditions, and developing an evidence-base for the management of diseases. The network joined forces with existing organisations – specifically Orphanet and Eurocat – in order to disseminate best-practice guidelines.

The project also launched the Dysmorphology Diagnostic System (DDS), a Web-based software tool that allows clinicians to electronically submit cases for diagnostic purposes to expert dysmorphologists via an interface hosted at one of over 60 designated “nodes”. Some 75 centres from 28 European countries were given access to the DDS software, which allows for the submission of undiagnosed dysmorphic cases for review via a standardised submission form, complemented by securely uploaded images and investigation results to members of a panel of 37 experts from 32 European Centres of Expertise. Within a remarkably brief 30 day period, submitting clinicians receive a report honed from a consensus of several expert opinions, complete with advice for further investigation - including molecular or cytogenetic testing, and suggestions for patient management. The traditional route for undiagnosed dysmorphology cases rests upon presentation at national or international meetings, taking place just a few times per year. A further advantage of the DDS is that it offers a wide pool of international expertise for each given case, for which experts can take the time to consult the literature and their own archives rather than trying to make an on-the-spot diagnosis that meeting consultations demand.

To date, the DDS has examined and suggested diagnoses for over 90 cases, involving a broad range of conditions – genetic, chromosomal, biochemical and environmentally caused. At least two or three new, previously-undescribed syndromes have been seen. The DDS allows experts to locate other similar cases and delineated specific phenotypes.

The final coup of the Dyscerne project is the completion of clinical practice guidelines for four rare conditions: Angelman, Kabuki, Noonan, and Williams syndromes. These excellently executed documents discuss diagnosis and provide detailed evidence-based recommendations for each aspect of disease management and treatment, organised into sections depending on the different body systems, within which considerations for distinct age groups are presented. Key references and relevant links are also furnished. These publications are freely available from the Dyscerne website and are simultaneously disseminated by Orphanet. Dyscerne is looking for experts willing to translate these guidelines into other languages.

EU funding has now ended for the Dyscerne project. The website is being maintained on a good-will basis. Similarly, the network continues and cases are still being accepted because the experts want to keep diagnosing rare syndromes. The founders are brainstorming for ideas to keep Dyscerne alive – including local funding and engaging doctoral students at the University of Manchester. But Dyscerne is a European project – and most benefits those submitting undiagnosed cases. A diagnosis can lead to a specific, tailored treatment plan. In the maelstrom of the cross-border directive controversy, where patients may or may not be allowed to travel for expert care and diagnostics they lack at home – Dyscerne offers an elegant, cost-effective solution where neither the patient nor the expert are required to travel – just the data. Dyscerne still hopes to expand beyond Europe. Indeed, it donated its software to a practitioner in Sri Lanka who had no other means of diagnosing unknown syndromic disorders. Those interested in acquiring the DDS software (the licence cost per account is less than 100 euros), should contact Dyscerne.

Spotlight on...
Dr. Atta ur-Rahman Fitrat: Trying to control thalassaemia and and other blood disorders in Afghanistan

The thalassaemias are a diverse group of genetic blood diseases characterised by absent or decreased production of normal haemoglobin, resulting in varying degrees of microcytic anaemia. A condition with a prevalence varying according to geographic region, thalassaemia may have developed as a defence against malaria and consequently, carriers of the disease may indeed be protected from malaria. Thalassaemia is one of a handful of rare conditions for which, due to existing treatment and management, patients can live a relatively normal life. But not in Afghanistan – a country shattered by decades of warfare.

The Life Saving Organization for Afghanistan (LSOA) was established with the aim of increasing access to quality health care, education, women empowerment, rural development, poverty reduction and orphan care. A non-government, non-political, non-profit, non-partisan national organisation established in 2007 and registered with the Health and Economic Ministries of Afghanistan, the LSOA is still in its developmental stages, and consequently seeks international support and guidance. Dr. Atta ur-Rahman Fitrat, Executive Director of LSOA, has been working in Pakistan on thalassaemia-related issues for the past five years. An Afghan national, he has been a consultant physician with different thalassaemia centres in Pakistan such as the Frontier and Hamza Thalassemia Foundations, and participates in the conferences, seminars and workshops of the Pakistan Thalassemia Federation.

Dr. ur-Rahman Fitrat is trying to develop diagnosis, treatment, prevention, and awareness resources for thalassaemia in Afghanistan. As in other under-developed countries, thalassaemia is on the rise in Afghanistan due to a constellation of factors – a lack of diagnostic facilities, consanguinity, illiteracy, and poverty. Afghanistan has a severe shortage of the blood necessary for transfusions that comprise thalassaemia treatment. Neither the overburdened Afghan government nor the international community have taken action on behalf of this particular group of patients. Presently, there are around 800 paediatric thalassaemic Afghan refugees who have been registered with different thalassaemia centres in Pakistan and who do not want to repatriate back to Afghanistan because of the lack of blood and other medical resources. OrphaNews Europe invited Dr. ur-Rahman Fitrat to describe the situation for thalassaemia patients in Afghanistan:

OrphaNews Europe: What are the goals of the Life Saving Organization for Afghanistan (LSOA) in the field of thalassaemia?

Dr. ur-Rahman Fitrat: The goal of the LSOA is to eradicate thalassaemia major from the most affected areas of Afghanistan (eastern zone and central provinces) and to prevent the spread of HIV among thalassaemia and haemophilia affected families by 2025.

OrphaNews Europe: What is the situation for thalassaemia patients in Afghanistan?

Dr. ur-Rahman Fitrat: Nothing has ever been done regarding the diagnosis, treatment and prevention of thalassaemia in the history of Afghanistan. The situation of thalassaemic patients in Afghanistan is unequal to patients in other countries due to the following factors: a lack of public awareness; most thalassaemic patients die before diagnosis; treatments (blood transfusion, iron chelation) are not available in time; people in Afghanistan are afraid of blood donation; and there is a total lack of awareness regarding prenatal diagnosis (CVS test) and genetic counselling for thalassaemic parents. Unfortunately, to date there is still no action toward the diagnosis, treatment and prevention of thalassaemia. Some patients are able to travel to Pakistan for blood transfusions and other treatments.

OrphaNews Europe: Are there any diagnostic facilities at all for thalassaemia in Afghanistan?

Dr. ur-Rahman Fitrat: According to the most recent information, thalassaemia diagnosis facilities are not available in any hospitals or clinics.

OrphaNews Europe: Do you have any figures concerning the prevalence of thalassaemia in Afghanistan?

Dr. ur-Rahman Fitrat: Many thalassaemia patents die before diagnosis and treatment, due to a lack of awareness, illiteracy, and general poor health conditions. Unfortunately data for these patients are not known. But it is recognised that thalassaemia is increasing each year. As neither the World Health Organization (WHO), the Islamic Republic of Afghanistan Ministry of Public Health (MoPH), nor other health supporting agencies have taken action, precise facts and figures concerning thalassaemia patients are unknown. According to our information, there are currently around 1500 major and intermedia thalassaemia patients. If the MoPH, the WHO, United Nations High Commissioner for Refugees (UNHCR), the United Nations Children’s Fund (UNICEF), or other health-related organisations and/or individual donors could pave the way for LSOA to conduct a survey of the entire country (34 provinces) to determine exact facts and figures of thalassemia minor, intermedia and major, data could be obtained within months.

OrphaNews Europe: There are some 800 Afghan children currently being treated in Pakistan who do not want to repatriate to Afghanistan because there are no medical facilities or supplies. Are these children separated from their families, or are their parents/families allowed to accompany them to Pakistan?

Dr. ur-Rahman Fitrat: These patients, accompanied by their families, live in Pakistan. They have been settled in Pakistan solely for the treatment of their children. If there were proper thalassaemia centres in Afghanistan, they would repatriate. We have shared this problem in written form with the UNHCR in Pakistan (Peshawar sub-office) and via telephone communications with the Kabul main office, but nothing has been done thus far. If UNHCR could address this issue of refugee repatriation, LSOA is ready for any kind of cooperation.

OrphaNews Europe: Is there any scheme for collecting blood donations and for performing transfusions in Afghanistan?

Dr. ur-Rahman Fitrat: Yes, there are efforts from the Afghan government, but they are too slow to meet the needs of the patients. LSOA appreciates these efforts and wants to reinforce them in a consistent manner throughout the country by a mass awareness-raising campaign for volunteer blood donations. This could be achieved via walks or marches, seminars, workshops, brochures and media involvement. Presently, volunteer blood donors are less than 2% in Afghanistan which is not enough for patients.

OrphaNews Europe: Does the country offer any kind of social security scheme to help pay for medicines and care for patients with thalassaemia and other rare conditions?

Dr. ur-Rahman Fitrat: Only government hospitals provide blood transfusions. There are no proper thalassaemia protocol treatments such as iron chelation therapy, splenectomy, or treatments for cardiac failure, hepatitis, endocrine disorders, or metabolic disorders. Nor is there genetic counselling for future babies.

OrphaNews Europe: You are a specialist on thalassaemia, but could you comment on other rare diseases and/or disabilities that you see in Afghanistan?

Dr. ur-Rahman Fitrat: Haemophilia, aplastic anaemia, von Willebrand disease, leukaemia, nephrotic syndrome, Cushing Syndrome, Willson disease, familial breast cancer and polio are amongst other rare diseases seen in Afghanistan and for which the prognosis is poor and unproductive.

OrphaNews Europe: Are there any resources for the education of children with cognitive deficits or physical limitations?

Dr. ur-Rahman Fitrat: I don’t think so.

OrphaNews Europe: What is the prevalence of consanguineous marriage in Afghanistan?

Dr. ur-Rahman Fitrat: More than 80%, because Afghanistan is a traditional society.

OrphaNews Europe: Are there medical scientific research institutions – either academic, hospital, or private - functioning in Afghanistan at this time?

Dr. ur-Rahman Fitrat: Nil. LSOA strives to establish a care and support programme for thalassaemia and other blood disorders care in five major zones I would like to call on relevant organisations working on blood disorders to contact us to establish a joint effort.

OrphaNews Europe: What do you most need at this time?

Dr. ur-Rahman Fitrat: My hope is to establish well equipped thalassaemia (and other blood disorder) control centres in Afghanistan. We need technical and financial support from Afghanistan’s supporting agencies – in particular the MoPH, WHO, UNHCR, UNICEF, the Islamic Development Bank, Islamic Relief UK, Muslim Aid UK, ADB, the World Bank, as well as individual donors. LSOA kindly requests the Acting Minister of Public Health of the Islamic Republic of Afghanistan, H.E Dr. Suraya Dalil to support LSOA. We also need the support of the Thalassemia International Federation (TIF) in order to establish an Afghanistan Thalassemia Society. We kindly appeal to individuals, as well as the above-mentioned respected organisations and firms to support the thalassaemia care programme in Afghanistan.

Contact Dr. Atta-ur-Rahman Fitrat:
Dr. Atta-ur-Rahman Fitrat
Executive Director
Life Saving Organization For Afghanistan (LSOA)


EU Policy News
New EU directive will regulate organ donations and transplantations
A directive proposal in the final phases of passage will establish common standards for safety and quality in the area of organ donation and transplantation – an issue pertinent to the scores of rare diseases that affect organs such as the heart, liver or kidneys. The new legislation seeks to level the playing field across Europe and offer protection to poor citizens vulnerable to illegal organ trafficking schemes. The European Parliament voted in mid-May to pass the directive, which is pending adoption by the Council of Ministers. The European Commission has also set forth a ten point action plan for organ transplantation and donation, which has been backed by the Parliament. Under the new legislation, each Member State (MS) must establish a national authority to monitor the safety and quality of both donations and transplantations. Recommendations have also been put forward for a database for organs and donors. Donation must be entirely voluntary and free from financial gain. There are presently some 60,000 Europeans awaiting organ transplantations - many with rare conditions.

Reflection paper on ethical and good clinical practice considerations for trials in third countries now open for consultation
There are a significant number of clinical studies that recruit patients from several regions – including countries outside the European Economic Area – for products that will be submitted for marketing authorisation within the EU. The European Medicines Agency has issued a reflection paper considering ethical and good clinical practice aspects for such trials conducted in third countries. The paper, open for consultation until 30 September 2010, seeks to ensure that so-called third country trials (countries beyond the European Economic Area) are conducted in accordance with existing principles of good clinical practice and ethical requirements. Such considerations are relevant to rare disease clinical trials, which, due to sparse and scattered patient populations, may indeed involve third country participation. For this population, post-trial treatment access is a particularly pertinent topic, especially for the often-expensive orphan drugs. Consult the reflection paper on third country clinical trial participation
First certification opinion issued by the Committee for Advanced Therapies
The European Medicines Agency’s Committee for Advanced Therapies (CAT) has tested its new certification system created to facilitate the process of advanced therapy product development amongst small and medium sized enterprises (SMEs). The CAT’s new certification procedure does not guarantee a marketing authorisation, but it sends a signal to potential investors that a sponsor is on the right track in terms of product development. An EMA press release elaborates that the certificate procedure, delineated in Commission Regulation (EC) No 668/2009 “… foresees that an SME submits to the Agency data on the quality and where available non-clinical data generated with an ATMP from an early stage of development. The CAT carries out a scientific evaluation of these data and may recommend the issuing of a certificate confirming to what extent the data generated so far comply with the review standards that would be applied for the evaluation of a marketing authorisation application”. This first certification opinion has been issued for a suspension of 5-50 107 mononuclear cells in 11 ml X-Vivo-10 medium containing 20 % autologous serum, indicated for acute myocardial infarction and chronic ischaemic heart disease.
Learn more about the CAT Certification system

EMA list of companies with SME status updated
The European Medicines Agencies has updated its list of companies with EMA Small-and-Medium Enterprise (SME) status. View the list

National & International Policy Developments
Sluggish economy temporarily bridles French rare disease plan momentum
The second French National Plan for Rare Diseases, elaborated during 2009 following an intense scrutiny of the successes and shortcomings of the first plan, has many hoops through which to jump. France’s initial National Plan for Rare Diseases – which ran from 2005-2008 - was the first of its kind in the world. The second plan has been streamlined to function as efficiently as possible while retaining all the elements essential to adequately care for the country’s over three million rare disease patients. The ten axes of the first plan have been pared to seven: Development Indicators; Health Care Coverage; Information and Training; Organisation of Care and Diagnostics; Targeted Medicines; Research; and European and International Cooperation. An initial draft of the second plan was unveiled in February before the four ministries concerned with the plan’s adoption and implementation. Following a review period, a revision was put forward and underwent inter-ministerial arbitrage on 26 March and again on 9 April. After a few more nips and tucks, the latest version of the plan was subject to a meeting addressing budgetary considerations. Due to the dismal economic situation still plaguing all of Europe, the rare disease plan has momentarily stalled in this phase of passage. OrphaNews Europe will inform readers the minute light appears at the end of the tunnel.
Learn more about France’s second plan for rare diseases

Australia rejects funding for “world’s most expensive drug”
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematopoietic stem cell disorder characterised by corpuscular hemolytic anemia, bone marrow failure and frequent thrombotic events. In Australia, where PNH is believed to affect only 75 persons, the government has decided not to fund eculizumab (Soliris) for treating PNH. Aside from the enormous cost of the treatment - which has been described as the world’s most expensive - the decision not to fund Soliris was based on the Pharmaceutical Benefits Advisory Committee’s uncertainty as to the comparative mortality benefit over best supportive care. The PNH Support Association of Australia is contesting the decision.
Serbia pilot tests cystic fibrosis newborn screening
In addition to neonatal screening for PKU and congenital hypothyroidism (since 2003), a pilot study for cystic fibrosis (CF) newborn screening has been initiated at the Institute for Child and Youth Health Care in Novi Sad, located in the northern Autonomous Province of Vojvodina in Serbia. The neonatal CF screening will take place at four regional maternity hospitals in the province, supported by the Provincial Secretariat for Health. The applied strategy includes the IRT-IRT screening protocol and sweat chloride test for confirming or excluding diagnosis. In cases with borderline sweat chloride values, mutation analysis of the CFTR gene will be performed at the Institute for Molecular Genetics and Genetic Engineering in Belgrade.
NIH seeks input on the creation of a registry for genetic testing
In the USA, the National Institutes of Health (NIH) has issued a Request for Information (RFI) seeking input on its plan to develop the Genetic Testing Registry (GTR). The GTR will be a “public resource that provides a centralised location for test developers, manufacturers, and researchers to voluntarily submit information about genetic tests such as their intended use, validity, and utility.” The NIH believes that transparent access to such information is vital to facilitate research and to enable informed decision making by patients, caregivers, health care providers, clinical laboratory personnel, payers, and policy makers. Individuals, groups, and organisations interested in commenting on the NIH plan to develop the GTR, as outlined in the RFI, may submit comments by 12 July 2010. The NIH is particularly interested in the types of tests and the types of data elements that should be included in the GTR. Comments will be made publicly available. Consult the Request for Information
Other European news
Pimary immune deficiency group petitions for early diagnosis and awareness-raising
The Primary Immune Deficiency (PID) Community and global charity the Jeffrey Modell Foundation (JMF) have launched a European Call to Action promoting early diagnosis of this class of over one hundred identified rare diseases. The petition, which has already obtained over 100 signatures, including 10 from Members of Parliament from seven different countries, also calls for the “appropriate treatment, physician education and public awareness in Europe” for this group of often un- or mis-diagnosed illnesses.
Other International News
Struggling with complexity – going beyond open-access publishing
Participants gathering in Leiden in May for the Third European Conference on Scientific Publishing in Biomedicine and Medicine churned over the complex topic of which computational approaches might best manage the explosion of medical-scientific information. The role of the publisher as facilitator of translational research was highlighted. Orphanet was singled out as an example of the “new librarian” – producing freely-accessible, quality, up-to-date translational information in five major languages for the medical and scientific communities. The open access journals offer the best cost-benefit ratio and it was also observed that the papers published in these journals are more often accessed. Regarding the effect on citation, there is only an effect on early citation which is due to early access. A plea was made for access to transparent, unbiased data for all European clinical trials – both negative and positive outcomes. Consult the conference abstracts.

In related news, a study published in the Canadian Medical Association Journal demonstrates that health professionals from developing countries are frequently unable to access research findings that could improve their practice – and patient outcome. The study, which looked at 1500 health professionals from 10 developing countries, found that less than 10% consult the leading medical and scientific publications, such as the Lancet or the New England Journal of Medicine. Only 18% of respondents had access to the Internet and just over 50% reported reading English adequately. Despite this, some 85% indicated a willingness to alter their practice based on research findings – using locally produced research in paper format clinical practice guidelines. The authors call for locally-adapted publications of research-based evidence from other settings as a possible solution. Finding a way to bring current knowledge to practitioners working with rare diseases could prove critical to patients in these countries. Consult the abstract

Genetic Alliance posts informative newborn screening playlist on YouTube

The Genetic Alliance, a non-profit genetics advocacy organisation, has created a video playlist featuring newborn screening from the perspectives of a variety of stakeholders. Available via the Genetic Alliance YouTube Channel, the videos are designed to foster learning and facilitate the exchange of ideas in the field of newborn screening. Created in part with funding from a cooperative agreement of the Genetic Services Branch, Maternal and Child Health Bureau, Health Resources and Services Administration in the USA, the YouTube forum allows viewers to exchange dialogue based on the videos. Amongst the topics covered are the frequently misunderstood issues of carrier status, false-positives, and more. It is hoped that the videos will better inform the public while also permitting stakeholders to learn more about the perspective of parents and families.


Ethical, Legal & Social Issues

Quality of life – what does it mean to the rare disease patient?
Quality of life (QoL) refers to “an individual’s sense of overall well-being encompassing physical, psychological, emotional, social, and spiritual dimensions”. This multi-faceted concept can mean different things to different researchers, resulting in a problematic lack of clarity. The authors of a new medical/scientific literature survey of rare disease QoL note that “Throughout the literature, the term QoL has been inexactly used to refer to a variety of related but conceptually distinct constructs, including functional health status, level of physical disability, clinical symptoms, psychological well-being, and mood.” Besides defining QoL is the question of how to measure it. Comparing QoL between different diseases as well as between different age groups adds to the complexity. Taking all these factors into account, the authors identified 58 studies of 30 distinct monogenic disorders employing a similar concept of QoL. Forty studies focused on adults, twelve on paediatric patients and six assessed QoL across the lifespan. Of the studies included, the authors note that all “… were descriptive in nature. Broadly, the descriptive aims can be summarized as: quantification (what is the QoL of affected individuals?), comparison (how does the QoL of affected individuals compare to unaffected individuals and/or patients with other chronic health conditions?), and correlation (what factors are associated with QoL?)” Analysis of the results found that “Genetic conditions have the potential to have major negative impact on individuals’ lives. Many of the studies found that QoL of affected individuals was significantly poorer than their unaffected counterparts. An important pattern emerged: physical and psychosocial aspects are perceived differently. Some studies found no impairment in physical domains of QoL, but significantly poorer psychosocial QoL compared to unaffected individuals. This demonstrates that individuals who are objectively ‘‘healthy’’ may still experience lower QoL. Factors beyond the physical manifestations of the disease influence QoL. Overall, the findings highlight the subjective nature of individuals’ perceptions of their QoL”. The authors hope that their study can “help elucidate how healthcare providers can more effectively enhance the QoL of patients affected with rare genetic conditions.”
Consult the PubMed abstract


Orphanet News

Orphanet offers readers a glimpse behind the scenes with its annual activity report
As part of its general policy of transparency, Orphanet, the reference portal for rare diseases and orphan drugs with partnerships in 38 pan-European countries, has published online its annual activity report for 2009. This document delineates the diverse activities of the network. A profile of the site’s users is provided, along with a progress report on the various tools, products and services that Orphanet developed or improved upon in 2009. There is also mention of Orphanet’s various international collaborations, communication activities, and a list of the network’s major funding sources.
Consult the 2009 Orphanet Activity Report

Several Orphanet Series Reports brought up to date
The Orphanet Series Reports cover pertinent rare disease topics and are updated regularly as new information becomes available. Amongst those recently brought up to date are the reports Prevalence or reported number of published cases listed in alphabetical order of disease ; Diseases listed by decreasing prevalence or number of published cases ; and Patient Registries in Europe.
New Orphanet Journal of Rare Diseases publications
Niemann-Pick disease type C
Congenital hypothyroidism


New Syndromes

Epibulbar lipodermoids, preauricular appendages and polythelia in four generations
A new syndrome with abnormalities along the first branchial arch and the milk list is described in a family of four affected generations. The characteristics of the syndrome are epibulbar lipodermoids, preauricular appendages and polythelia. The expressivity varies but all affected have supernumerary nipples and preauricular manifestations while visible epibulbar lipodermoids do not seem obligatory. The syndrome has a typical dominant pattern of heredity.
Read the PubMed abstract

Ophthalmic Genet ; 81-83 ; June 2010

New Genes

Retinitis pigmentosa: a splice-site mutation in a retina-specific exon of BBS8 at cause for nonsyndromic form
Tissue-specific alternative splicing is an important mechanism for providing spatiotemporal protein diversity. Here the authors show that an in-frame splice mutation in the gene BBS8, involved in pleiotropic Bardet-Biedl syndrome (BBS), is sufficient to cause nonsyndromic retinitis pigmentosa (RP). Understanding the role of this additional sequence might inform the mechanism of retinal degeneration in patients with syndromic BBS or other related ciliopathies.
Read the PubMed abstract

To read more about "Retinitis pigmentosa"

Am J Hum Genet ; 805-812 ; 14 May 2010
Tarp syndrome: RBM10 at cause
Micrognathia, glossoptosis, and cleft palate comprise one of the most common malformation sequences, Robin sequence. It is a component of the TARP syndrome: Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left superior vena cava. This disorder is X-linked and severe, with apparently 100% pre- or post-natal lethality in affected males. Here the authors characterise a second family and show that TARP syndrome is caused by mutations in the RBM10 gene, which encodes RNA binding motif 10. The authors further show that this previously uncharacterised gene is expressed in midgestation mouse embryos in the branchial arches and limbs, consistent with the human phenotype.
Read the PubMed abstract

To read more about "TARP syndrome"

Am J Hum Genet ; 743-748 ; 14 May 2010
Amyotrophic lateral sclerosis has mutations in the gene encoding optineurin
Amyotrophic lateral sclerosis (ALS) has onset in middle age and is a progressive disorder characterised by degeneration of motor neurons of the primary motor cortex, brainstem and spinal cord. Most cases of ALS are sporadic, but about 10% are familial (FALS), for which specific genetic defects have been found in only 20-30% of cases. Here the authors show that there are mutations in the gene encoding optineurin (OPTN), earlier reported to be a causative gene of primary open-angle glaucoma, in patients with ALS. Their findings strongly suggest that OPTN is involved in the pathogenesis of ALS. They also indicate that NF-kappaB inhibitors could be used to treat ALS and that transgenic mice bearing various mutations of OPTN will be relevant in developing new drugs for this disorder.
Read the PubMed abstract

To read more about "Amyotrophic lateral sclerosis"

Nature ; 223-226 ; 13 May 2010
Congenital mirror movements: mutations in DCC at cause
Mirror movements are involuntary contralateral movements that mirror voluntary ones and are often associated with defects in midline crossing of the developing central nervous system. The authors studied two large families, one French Canadian and one Iranian, in which isolated congenital mirror movements were inherited as an autosomal dominant trait. They found that affected individuals carried protein-truncating mutations in DCC (deleted in colorectal carcinoma), a gene on chromosome 18q21.2 that encodes a receptor for netrin-1, a diffusible protein that helps guide axon growth across the midline. Functional analysis of the mutant DCC protein from the French Canadian family revealed a defect in netrin-1 binding. Thus, DCC has an important role in lateralization of the human nervous system.
Read the PubMed abstract

Science ; 592 ; 30 April 2010
Cenani-Lenz syndrome: two separate studies define the role of LRP4 mutations
Two separate studies identify and elaborate the function of LRP4 mutations in Cenani-Lenz syndrome, a congenital malformation syndrome defined as complete and complex syndactyly of the hands combined with malformations of the forearm bones and similar manifestations in the lower limbs. The first study identified recessive LRP4 mutations in 12 families. The second study used gene targeting to create an Lrp4 null mouse line. The mutation resulted in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. .
Read the first PubMed abstract
Read the second PubMed abstract

To read more about "Syndactyly, Cenani-Lenz type"

Am J Hum Genet ; 696-706 ; 14 May 2010
PLoS One ; e10418 ; 29 April 2010
Autosomal-recessive nonsyndromic sensorineural hearing loss: a truncating mutation in SERPINB6 is associated
More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, the authors mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DFNB91) to chromosome 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. They subsequently identified a nonsense mutation (p.E245X) in SERPINB6, which is located within the linkage interval for DFNB91 and encodes for an intracellular protease inhibitor. They also demonstrated that SERPINB6 was expressed primarily in the inner ear hair cells, plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss.
Read the PubMed abstract

To read more about "Autosomal recessive nonsyndromic sensorineural deafness type DFNB"

Am J Hum Genet ; 797-804 ; 14 May 2010

Research in Action

Fundamental Research
Joubert syndrome: Arl13b functions at ciliary membranes and stabilises protein transport in Caenorhabditis elegans
The small ciliary G protein Arl13b is required for cilium biogenesis and sonic hedgehog signalling and is mutated in patients with Joubert syndrome (JS). The authors showed that Arl13b/ARL-13 localisation is frequently restricted to a proximal ciliary compartment, where it associates with ciliary membranes via palmitoylation modification motifs. They found that loss-of-function C. elegans arl-13 mutants possess defects in cilium morphology and ultrastructure, as well as defects in ciliary protein localization and transport; ciliary transmembrane proteins abnormally accumulate, PKD-2 ciliary abundance is elevated, and anterograde intraflagellar transport (IFT) is destabilised. Finally, they show that arl-13 interacts genetically with other ciliogenic and ciliary transport-associated genes in maintaining cilium structure/morphology and anterograde IFT stability.
Read the PubMed abstract

To read more about "Joubert syndrome"

J Cell Biol ; 953-969 ; 22 March 2010
Myelodysplastic syndrome: the Apc(min) mouse has altered hematopoietic stem cell function and provides a disease model
Apc, a negative regulator of the canonical Wnt signaling pathway, is a bona-fide tumuor suppressor whose loss of function results in intestinal polyposis. APC is located in a commonly deleted region on human chromosome 5q, associated with myelodysplastic syndrome (MDS), suggesting that haploinsufficiency of APC contributes to the MDS phenotype. Analysis of the hematopoietic system of mice with the Apc(min) allele that results in a premature stop codon and loss of function showed no abnormality in steady state hematopoiesis. Bone marrow derived from Apc(min) mice showed enhanced repopulation potential, indicating a cell intrinsic gain of function in the long-term hematopoietic stem cell (HSC) population. However, Apc(min) bone marrow was unable to repopulate secondary recipients because of loss of the quiescent HSC population. Apc(min) mice developed a MDS/myeloproliferative phenotype. These data indicate that Wnt activation through haploinsufficiency of Apc causes insidious loss of HSC function that is only evident in serial transplantation strategies.
Read the PubMed abstract

To read more about "Myelodysplastic syndromes"

Blood ; 3489-3497 ; 29 April 2010
Fanconi anaemia genes in human embryonic stem cells reveal early developmental defects in the hematopoietic lineage
Fanconi anaemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterised by paediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. The authors created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). They show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. The data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA.
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To read more about "Fanconi anemia"

Blood ; 3453-3462 ; 29 April 2010
Oculopharyngeal muscular dystrophy: mouse model reveals severe atrophy restricted to fast glycolytic fibres
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterised by ptosis, dysphagia and proximal limb weakness. Using a transgenic mouse model of OPMD (A17.1) and performing transcriptomic studies combined with a detailed phenotypic characterisation of this model at three time points revealed a massive gene deregulation among which the authors identified a significant deregulation of pathways associated with muscle atrophy. Using a mathematical model for progression, they identified that one-third of the progressive genes were also associated with muscle atrophy. Functional and histological analysis of the skeletal muscle of this mouse model confirmed a severe and progressive muscular atrophy associated with a reduction in muscle strength. Moreover, muscle atrophy in the A17.1 mice was restricted to fast glycolytic fibres, containing a large number of intranuclear inclusions (INIs). These results demonstrate a fibre-type specificity of muscle atrophy in this OPMD model.
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To read more about "Oculopharyngeal muscular dystrophy"

Hum Mol Genet ; 2191-2207 ; 1 June 2010
Heterotaxy and VACTERL association: the ZIC3 gene links both disorders in a newborn male
A male newborn is reported with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of this patient overlaps with that of X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced and a 6-nucleotide insertion was found that is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. This novel mutation was not present in the mother, nor in 336 chromosomes from 192 ethnically matched controls. It is hypothesised that this novel and de novo polyalanine expansion in the ZIC3 gene contributes to the VACTERL association in this patient.
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To read more about "VATER association"
To read more about "Heterotaxia"

J Med Genet ; 351-355 ; May 2010
Clinical Research
Cystic fibrosis: paternally imprinted locus on 7q34 is a modulator
Cystic fibrosis (CF) is a monogenic disease characterised by a high variability of severity and outcome that points to the role of environmental factors and modulating genes that shape the course of this multi-organ disease. The authors identified a paternally imprinted locus on 7q34 as a modulator of cystic fibrosis disease severity, showing that imprinted elements can be identified by straightforward fine mapping of break points in sib pairs with informative contrasting phenotypes.
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To read more about "Cystic fibrosis"

Eur J Hum Genet ; 553-559 ; May 2010
Williams-Beuren syndrome: partial 7q11.23 deletions further implicate GTF2I and GTF2IRD1 as cause of neurocognitive profile
Williams-Beuren syndrome (WBS) is a developmental disorder with multisystemic manifestations mainly characterised by vascular stenoses, distinctive craniofacial features, intellectual deficit with a characteristic neurocognitive profile, and some endocrine and connective tissue abnormalities, caused by a recurrent deletion of 1.55 Mb including 26-28 genes at chromosomal region 7q11.23. The analysis of clinical-molecular correlations in a few reported atypical patients has been useful to propose several deleted genes as main contributors to specific aspects of the WBS phenotype. Two additional families with partial phenotypes and atypical 7q11.23 deletions were studied here. Deletions were precisely defined at the nucleotide level, and the expression levels of some affected and flanking genes were assessed in lymphoblastoid cell lines. Clinical-molecular correlations in these two families further confirm that the functional hemizygosity for the GTF2I and GTF2IRD1 genes is the main cause of the neurocognitive profile and some aspects of the gestalt phenotype of WBS.
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To read more about "Williams syndrome"

J Med Genet ; 312-320 ; May 2010
Tetralogy of Fallot: comprehensive genotype-phenotype analysis in 230 patients
Tetralogy of Fallot (ToF), the most frequent cyanotic congenital heart disease, is associated with a wide range of intra- and extra-cardiac phenotypes. In order to get further insight into genotype-phenotype correlation, a cohort of 230 unselected patients with ToF was comprehensively investigated. This study shows that 22q11.2 deletion represents the most common known cause of ToF, and that the associated cardiac phenotype is distinct for obstruction of the proximal pulmonary artery, hypoplastic central pulmonary arteries and subclavian artery anomalies. Atrioventricular septal defect associated with ToF is very suggestive of trisomy 21 and almost excludes 22q11.2 deletion. A further patient with a recurrent polyalanine stretch elongation within the TBX1 gene links for the first time TBX1 cytoplasmatic protein aggregation to congenital heart defects.
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To read more about "Tetralogy of Fallot"

J Med Genet ; 321-331 ; May 2010
Reciprocal 16p11.2 rearrangements: molecular and phenotype characterisation
Deletion and the reciprocal duplication in 16p11.2 were recently associated with autism and developmental delay. In this study, the authors show that recurrent reciprocal 16p11.2 deletion and duplication are characterised by a spectrum of primarily neurocognitive phenotypes that are subject to incomplete penetrance and variable expressivity. The autism and macrocephaly observed with deletion and ADHD and microcephaly seen in duplication patients support a diametric model of autism spectrum and psychotic spectrum behavioural phenotypes in genomic sister disorders.
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J Med Genet ; 332-341 ; May 2010
Gene Therapy
Leukodystrophy: enzymatic correction of CNS tissues by single intracerebral injection of therapeutic lentiviral vector
Leukodystrophies are rare diseases caused by defects in the genes coding for lysosomal enzymes that degrade several glycosphingolipids. Gene therapy for leukodystrophies requires efficient distribution of the missing enzymes in CNS tissues to prevent demyelination and neurodegeneration. In this work, the authors targeted the external capsule (EC), a white matter region enriched in neuronal projections, with the aim of obtaining maximal protein distribution from a single injection site and report that LV-mediated gene delivery of lysosomal enzymes by targeting highly interconnected CNS regions is a potentially effective strategy that, combined with a treatment able to target the PNS and peripheral organs, may provide significant therapeutic benefit to patients affected by leukodystrophies.
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To read more about "Leukodystrophy"

Hum Mol Genet ; 2208-2227 ; 1 June 2010
Sanfilippo syndrome type B: efficacy of bone marrow transplant, intracranial AAV-mediated gene therapy, or both, in mouse model
Sanfilippo syndrome type B (MPS IIIB) is a lysosomal storage disease resulting from a deficiency of N-acetyl-glucosaminidase (NAGLU) activity. In an attempt to correct the disease in the murine model of MPS IIIB, neonatal mice were treated with intracranial AAV2/5-NAGLU (AAV), syngeneic bone marrow transplant (BMT), or both (AAV/BMT). All treatments resulted in some improvement in clinical phenotype. AAV alone is more efficacious than BMT or AAV/BMT treatment for lifespan. BMT was the least efficacious treatment by all measures. CNS-directed AAV treatment alone appears to be the preferred treatment, combining the most efficacy with the least toxicity of the approaches assessed.
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To read more about "Sanfilippo syndrome type B"

Mol Ther ; 873-880 ; May 2010
Therapeutic Approaches
Huntington disease: rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model
Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in huntingtin. There are no treatments to slow the neurodegeneration caused by this mutation. Mutant huntingtin causes disease via a toxic gain-of-function mechanism and has the propensity to aggregate and form intraneuronal inclusions. One therapeutic approach for HD is to enhance the degradation of the mutant protein. The authors have shown that this can be achieved by upregulating autophagy, using the drug rapamycin. In order to find safer ways of inducing autophagy for clinical purposes, they previously screened United States Food and Drug Administration-approved drugs for their autophagy-stimulating potential. This screen suggested that rilmenidine, a well tolerated, safe, centrally acting anti-hypertensive drug, could induce autophagy in cell culture via a pathway that was independent of the mammalian target of rapamycin. Here they show that rilmenidine induces autophagy in mice and in primary neuronal culture. Rilmenidine administration attenuated the signs of disease in a HD mouse model and reduced levels of the mutant huntingtin fragment.
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To read more about "Huntington disease"

Hum Mol Genet ; 2144-2153 ; 1 June 2010
Mitochondrial DNA disease: pronuclear transfer in human embryos to prevent transmission
Mutations in mitochondrial DNA (mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births and at least 1 in 10,000 adults in the UK are affected by mtDNA disease. Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease. Here the authors show that transfer of pronuclei between abnormally fertilised human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure they found the average level of carry-over after transfer of two pronuclei is less than 2.0%, with many of the embryos containing no detectable donor mtDNA.
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To read more about "Mitochondrial disease"

Nature ; 82-85 ; 6 May 2010
Diagnostic Approaches

Danon disease: utility of real-time 3-dimensional echocardiography and magnetic resonance imaging for evaluation
Danon disease – also referred to as glycogen storage disease due to LAMP-2 (Lysosomal-Associated Membrane Protein 2) deficiency - is a lysosomal glycogen storage disease characterised by severe cardiomyopathy and variable degrees of muscle weakness, frequently associated with intellectual deficit. The disease classically manifests in males over 10 years of age. The clinical picture may be severe in both sexes, but onset generally occurs later in females. The authors describe a precise, non-invasive diagnostic approach based on 3-dimensional echocardiography, which permits characterisation of the myocardia tissue and cardiac function, coupled with magnetic resonance imaging in order to distinguish ischemic and non-ischemic disease forms.
Read the PubMed abstract

To read more about "Glycogen storage disease due to LAMP-2 deficiency"

Circulation ; e390-e392 ; 4 May 2010

Patient Management and Therapy

Cushing disease: pasireotide - alone or with cabergoline and ketoconazole
Cushing disease is characterised by endogenous hypercortisolism from ACTH hypersecretion by adenoma. The authors present the results of a prospective multicentric trial evaluating the effect of three molecules on the level of urinary cortisol: first, pasireotide, then pasireotide with cabergoline added, and finally the combination of pasireotide, cabergoline and ketoconazole. Some 90% of 17 patients showed a promising response to the combined treatment.
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To read more about "Cushing disease"

N Engl J Med ; 1846-1848 ; 13 May 2010
End-of-life experience of children undergoing stem cell transplantation for malignancy: parent and provider perspectives
The end-of-life (EOL) experience of children who undergo stem cell transplantation (SCT) may differ from that of other children with cancer. To evaluate perspectives and patterns of EOL care after SCT, the authors surveyed 141 parents of children who died of cancer and their physicians. Chart review provided additional information. Children for whom SCT was the last cancer therapy (n = 31) were compared with those for whom it was not (n = 110). SCT parents and physicians recognised no realistic chance for cure later than non-SCT peers and were more likely to have a primary goal of cure at death. SCT children were more likely to suffer highly from their last cancer therapy and die in the intensive care unit, with less opportunity for EOL preparation. SCT parents who recognised no realistic chance for cure more than 7 days before death along with the physician were more likely to prepare for EOL, and if their primary goal was to reduce suffering, to achieve this. SCT is associated with significant suffering and less opportunity to prepare for EOL. Children and families undergoing SCT may benefit from ongoing discussions regarding prognosis, goals, and opportunities to maximize quality of life.
Read the PubMed abstract

Blood ; 3879-3885 ; 13 May 2010

Orphan Drugs

A study of Belgium’s orphan drug reimbursement practices could prove useful to other countries
A group of authors based in Belgium has produced two intriguing studies – one in English and the other in French language – that take stock of the orphan drug situation in Belgium and beyond. Budget impact analysis of orphan drugs in Belgium: estimates from 2008 to 2013, appearing in the May issue of the Journal of Medical Economics is the first study of its kind to measure the impact of orphan drug expenditures on a country’s overall medicinal product budget. Determining the total orphan drug costs in Belgium in 2008, the authors then forecast the impact over the next five years. Using multiple sources, the authors calculate that orphan drug product expenditures (€66.2 million) comprised 5% of the country’s total hospital drug budget in 2008 and that the impact “is substantial and rising, thereby putting pressure on total drug expenditure in coming years”. The increase can be attributed to the growing number of orphan medicinal products receiving marketing authorisation in the EU. To estimate the future impact, the study contemplated three scenarios “reflecting different levels of growth in the number of drugs that gain marketing authorization in the European Union, the number of drugs that gain reimbursement in Belgium, and the average annual cost per patient per drug in Belgium”. The study can be instructive to other European countries trying to determine the impact of orphan drugs on their health budgets. The second, French language article, appearing in the Journal de Pharmacie de Belgique takes a look at the policies governing orphan drug development and authorisation. The authors call for the creation of European-level registries in order to follow the evolution of rare diseases as well as the “efficacy of orphan medicines, the majority of which are relatively expensive”. The authors also recommend a mechanism for evaluating reimbursement requests, in order to “ensure a coherent application of reimbursement criteria”. The authors compare specific practices amongst European countries – particularly Belgium, France, Sweden, the United Kingdom and Italy. Italy, for example, requires a patient to enrol in a national registry prior to dispensing a particular orphan product. Many countries (with the exception of Sweden and the UK) look to their neighbours when it comes to determining a price for a specific product. The authors assert that this practice leads sponsors to seek distribution first in those countries where obtaining the desired price is easier. For Belgium, the authors recommend establishing a “unique counter” within the social security agency that would centralise all reimbursement requests and could oversee a standardised registry system similar to that used in Italy.
Consult the first PubMed abstract
Consult the second PubMed abstract

A busy month for the COMP with 20 positive opinions adopted at the June meeting
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) adopted a whopping 20 positive opinions issued at the June 2010 COMP meeting for the treatment of:

- primary myelofibrosis
- post-polycythaemia vera myelofibrosis
- post-essential thrombocythaemia myelofibrosis
- low-flow priapism
- ovarian cancer
- familial adenomatous polyposis
- acute myeloid leukaemia
- mucopolysaccharidosis type IIIA (Sanfilippo A syndrome)
- epidermolysis bullosa
- acute myeloid leukaemia
- thromboangiitis obliterans (Buerger disease)
- molybdenum cofactor deficiency type A
- cystinosis
- chronic lymphocytic leukaemia
- glioma
- tuberculosis
- cystic fibrosis
- haemophilia A (two products)
- malignant mesothelioma

Consult the Orphanet list of orphan drugs authorised for marketing in Europe


Courses & Educational Initiatives

4th Inborn Errors in Neonatology Course
Date: 21-23 October 2010
Venue: Dubrovnik, Croatia

This practical course is run by an experienced team of paediatricians, neonatologists, molecular biologists and biochemists specialised in metabolic medicine, who already contributed substantially to the understanding of metabolic disorders in childhood. The two and a half days course includes lectures and seminars for 35 participants. The course is aimed at paediatricians with about 2-3 years clinical experience in the neonatology field.

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?

16th Retina International World Congress
Date: 26- 27 June 2010
Venue: Stresa, Italy

This year’s theme is “Change our vision – Bridging the gap from the lab to the patients”. Sessions will cover genetic and clinical aspects of inherited retinal degenerations; diagnosing young children; gene therapy; and treatment perspectives.
For further details

International Congress for Tarlov Cysts and Adhesive Arachnoiditis
Date: 2-3 July 2010
Venue: Chambéry, France

International health professionals will discuss recent findings on Tarlov and meningeal cysts, Arachnoïditis, Cauda Equina syndrome, and neuropathic pain. Patients will share their experience. Translations available in English, French and Spanish.
For further details

Fifth Eastern European Conference for Rare Diseases and Orphan Drugs and First Russian Conference for Rare Diseases
Date: 2-4 July 2010
Venue: Saint Petersburg, Russia

With sessions on Rare Diseases in the Focus of Personalized Medicine; Best Practice in Field of Rare Diseases and Personalized Medicine; Rare Diseases – Future, Perspectives, Challenges of Health Care; Modern capabilities in diagnostics and treatment of rare diseases; and much more.
For further details

14th International Conference on Behçet Disease
Date: 8-10 July 2010
Venue: London, England

Presenting new developments in basic and clinical science to bear on the specific issues of Behçet Disease (BD). Topics to be covered will include immunology of BD, vasculitis in BD, genetic basis of BD, regional inflammation and paediatric BD. The programme will also include debates on topics of current interest or controversy.
For further details

17th International Paediatric Colorectal Club Meeting
Date: 17-19 July 2010
Venue: Padova, Italy

Topics include anomalies of the bowel, anorectal malformation, Hirschsprung disease and urological aspects.
For further details

2th International Congress on Neuromuscular Diseases
Date: 17-22 July 2010
Venue: Naples, Italy

Offering a variety of sessions including paediatric neuromuscular diseases, genetic testing and diagnosis, pathogenic mechanisms of inherited neuropathies, novel therapeutic targets at the neuromuscular junction, motor neuron diseases, and much more.
For further details

International All Star Vasculitis Symposium
Date: 30 July-1 August 2010
Venue: Long Beach, CA, USA

Topics will cover all the vasculitides and will concentrate on the advances in medical treatments, research and quality of life issues for patients.
For further details

FDA Orphan Drug Workshop
Date: 3-4 August 2010
Venue: Minnesota, USA

Over two days, FDA staff from the Office of Orphan Products Development (OOPD) will provide regulatory assistance to sponsors to find regulatory paths forward. Most of the time will be spent in application writing and individual one-on-one guidance sessions to develop the strongest possible orphan designation application to be submitted at the close of the workshop.
For further details

26th International Congress of Pediatrics
Date: 4-9 August 2010
Venue: Johannesburg, South Africa

Amongst the general programme are symposia on primary immunodeficiency diseases in resource-limited settings, appropriate genetic testing, and a workshop on approaches to the dysmorphic child.
For further details

2nd Congress of the European Society for Paediatric Anaesthesiology
Date: 2-4 September 2010
Venue: Berlin, Germany

Amongst the programme of this congress will be a session entitled “Rare diseases: a common problem!” featuring the anaesthetic management of a child with a rare disease; approaches to rare diseases at the national and European level; and the OrphanAnaesthesia project.
For further details

International Society for Cellular Therapy (ISCT Europe) Second Regional meeting
11-14 September 2010
Belgirate, Italy

The ISCT is the global forum and resource for developing and supporting innovative cellular therapies through communication, education, and training, thus furthering clinical based investigation for the benefit of patients. Topics of this European regional meeting will include hematopoietic stem cells, mesenchymal stromal cells, immunotherapy, gene therapy, tissue engineering, new emerging therapies, legal and regulatory affairs, prenatal issues: cord blood, placenta and umbilical cord.
For further details

MEN 2010: 12th International Workshop on Multiple Endocrine Neoplasia
Date: 16-18 September 2010
Venue: Viareggio, Italy

This two-day meeting will provide a forum for educating basic and clinical investigators on the most recent advances in the area of hereditary endocrine tumours.
For further details

Second AnEUploidy Workshop
Date: 17-19 September 2010
Venue: Split, Croatia

AnEUploidy is the acronym of an Integrated Project (IP) funded by the European Commission within its Sixth Framework Programme. This project aims to contribute to the understanding of the molecular basis and pathogenic mechanisms of aneuploidies. This second workshop will allow colleagues to share views, advancements, and ideas.
For further details

International Meeting on Fibrous Dysplasia of Bone/McCune-Albright Syndrome: Best Clinical Practice and Future Research
Date: 3-5 October 2010
Venue: Bethesda, Maryland, USA

This conference will gather experts to develop a consensus on the best current medical and surgical treatment of fibrous dysplasia, MAS and Cherubism, to define areas of focus for future research, and to establish parameters for a registry/bio repository to aid research. Participants in the meeting include paediatric and adult orthopaedic specialists, cranio facial surgery, plastic surgery, endocrinology, and specialists in stem cells, microbiology and pathology from the USA, Israel, Italy, and Taiwan.
For further details

2nd European Rett Syndrome Conference
Date: 7-10 October 2010
Venue: Edinburgh, Scotland

Sessions include clinical and molecular update on MECP2 and Rett Syndrome; non coding RNAs & brain development; lessons from other diseases and other models; treatments and trials; outcome measures, international collaborations; and current perspectives and next steps.
For further details

15th International Congress of World Muscle Society
Date: 12-16 October 2010
Venue: Kumamoto, Japan

The main topics to be addressed include new therapeutic targets for neuromuscular disorders; congenital muscular dystrophies (celebrating the 50th anniversary of Fukuyama congenital muscular dystrophy); and distal myopathies and protein aggregation myopathies.
For further details

26th Annual Meeting of the Histiocyte Society
Date: 18–20 October 2010
Venue: Boston, Massachusetts USA

This year’s scientific programme will feature presentations by several experienced researchers regarding a variety of perspectives on the histiocytic disorders.
For further details

4th International Meeting on the Congenital disorders of glycosylation and related disorders
13-14 January 2011
Leuven, Belgium

The meeting will cover all aspects of these disorders, including the discovery of novel types, the study of fundamental aspects of glycosylation, analytical procedures and diagnostic methods and the analysis of models for the disease. The meeting is organized by EUROGLYCANET, a European network for the advancement of research, diagnosis and treatment of a growing group of rare disorders. The call for abstracts will open shortly.
For further details


Press & Publications

Spanish language article proposes conceptual framework for rare diseases
Dr. Francesc Palau, scientific director of Spanish rare disease biomedical research network CIBERER and Orphanet-Spain team coordinator, has published an article entitled Rare Diseases, an Emergent Paradigm in the Medicine of the XXI Century in the journal Medicina Clínica. This Spanish language article proposes a conceptual framework for rare diseases and suggests an integral model of health care through which health systems could meet the collective needs of patients and others involved in rare diseases.
View the PubMed abstract


Orphanews Europe, the newsletter of the Rare Diseases Task Force
Orphanews Europe is supported by the European Commission's DG SANCO
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Raphaël Demonchy, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Paloma Tejada, Aurélie Vandeputte
National Contact Point: Till Voigtländer (Austria), Jean Jacques Cassiman (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), Andres Metspalu (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann (Germany), Michael Petersen (Greece), János Sándor (Hungary), Andrew Green (Ireland), Judith Melki (Israel), Bruno Dallapiccola and Domenica Taruscio (Italy), Andre Megarbane (Lebanon), Vaidutis Kucinskas (Lithuania), Alfred Cuschieri (Malta), Abdelaziz Sefiani (Morocco), Martina Cornel (Netherlands), Stein Are Aksnes (Norway), Jolanta Sykut-Cegielska (Poland), Jorge Sequeiros (Portugal), Dragica Radojkovic (Serbia), Ludovit Kadasi (Slovakia), Borut Peterlin (Slovenia), Miguel del Campo and Manuel Posada de la Paz (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Habiba Chaabouni-Bouhamed (Tunisia), Fatmahan Atalar and Ugur Ozbek (Turkey), Edmund Jessop and Idoia Gomez-Paramio (United Kingdom)
For more information on the Rare Diseases Task Force
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