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The European Commission publishes its implementation report on rare diseases: Europe’s challenges and council recommendations

Since the European Commission’s Communication on Rare Diseases: Europe’s challenge of 2008 and the Council’s Recommendation on an action in the field of rare diseases of 2009, significant achievements have been accomplished and initiatives launched to improve rare disease diagnosis and care in EU Member States. The Commission Communication aimed to enhance recognition, support Member State policy and develop EU harmonisation and regulation in the field of rare diseases. The Council’s Recommendation appealed to Member States to implement national plans on rare disease management and aimed to define, code and record rare diseases, increase research, build European Reference Networks, gather EU expertise, empower patient organisations and develop sustainability.

Earlier this month, the Commission published its implementation report on the Commission Communication and Council Recommendation, outlining accomplishments and lessons learnt for further action. The Commission co-funded the EUROPLAN project and EUCERD Joint Action to help Member States develop, implement and evaluate their national plans and strategies for rare disease policy and classification. To date, sixteen Member States have proposed a national plan on rare diseases and a further seven are in the process of developing their strategy.

The Council Recommendation stipulates that Member States must establish clear and common definitions of rare diseases. Member States with national plans have adopted EU definitions of rare diseases and use the International Classification of Diseases ICD-9 or ICD-10 systems. Some Member States have begun introducing ORPHA codes in parallel, developed by the Orphanet Joint Action, since
ICD-9 and ICD-10 do not include most rare diseases. To increase the presence of rare diseases in international nomenclature, the EUCERD Joint Action is contributing to the WHO ICD-11 draft.

Via its Seventh Framework Programme for Innovation and Technology Development (FP7), the EU has funded some 120 multidisciplinary research projects on rare diseases. Projects such as E-RARE-2 coordinate and strengthen multidisciplinary and multi-national projects. Launched in 2011, IRDiRC’s
41-member consortium illustrates the EU’s ongoing commitment to promote international collaboration on rare disease research. The Commission aims to further harmonise research through a
European Platform on Rare Diseases Registration, centralising information on patient registries accessible to all stakeholders.

In accordance with Article 12 of Directive 2011/24/EU on the application of patients’ rights in cross-border healthcare and based on ten pilot projects, the Commission is developing European Reference Networks to establish collaborative centres of expertise on rare diseases. Pooling expertise from Member States into reference centres will help harmonise best practice, diagnostic and screening techniques, and patient care. The Commission also aims to facilitate access to orphan products that are not systematically approved in all Member States. Member States were invited to join the Mechanism of Coordinated Access to orphan medicinal products (MoCA) project, under the EU’s Platform on access to medicines in Europe, to increase cooperation between regulatory authorities and companies on the assessment of orphan medicinal products. The Medicine Evaluation Committee (MEDEV), the group of experts on reimbursement hosted by the European Social Insurance Platform (ESIP), offered to take forward a MoCA pilot project to improve access to orphan medicinal products in Europe.

The Commission is confident the Communication and Council Recommendation have reached their objectives to strengthen collaboration among EU Member States and with relevant stakeholders. This implementation report measures both achievements and future strategies to continue improving rare disease research and treatment, as well as the quality of life of patients and their families. While the recent advances presented in this report are encouraging, the Commission acknowledges the considerable efforts still required to ensure all rare disease patients are adequately cared for throughout the EU. The Commission intends to achieve this through the new Health Programme and EU Research and Innovation Programme Horizon 2020.

Read the implementation report


EC Expert Group
Report from the July 2014 meeting of the Commission Expert Group on Rare Diseases
The Expert Group on Rare Diseases held its second meeting last July in Luxembourg. Experts discussed recommendations on improving rare disease codification and registries. Member State representatives provided updates on national plans for rare diseases. Members discussed orphan medicinal product reimbursement in the EU. Details of the expansion of European Reference Networks (ERNs) for rare diseases were discussed. Experts discussed Horizon 2020 calls for support on projects in the field of rare diseases.

Read the report


EU Policy News
President-elect Jean-Claude Juncker’s decision to transfer the EMA from DG Health and Consumers to DG Enterprise and Industry provokes a wave of alarm and heavy criticism
On 10th September, European Commission President-elect Jean-Claude Juncker unveiled the new College of Commissioners’ composition. Having been transferred from DG Enterprise and Industry (ENTR) to DG Health and Consumers (SANCO) in 2009—following President José Manuel Barroso's decision—, the European Medicines Agency (EMA) and pharmaceutical policy responsibilities have been returned to DG ENTR, under the responsibility of Commissioner Elżbieta Bieńkowska.

While Mr Barroso’s 2009 move was widely awaited and welcomed as it focused priority on public health, Mr Juncker’s decision has come under intense criticism from the public health community. The president of the European Public Health Alliance (EPHA), Peggy Maguire, believes this reshuffle to be “a potential disaster”. In its press release of 12th September, the EPHA states that it “cannot support this decision which threatens Europe’s ability to prepare for major health crises such as outbreaks of infectious diseases, whilst putting the public interest behind the drive for profits in drug authorisation procedures”.

Health Action International (HAI) further warns the reshuffle “will put the commercial, profit-driven interests of the pharmaceutical industry, rather than patients and consumers, at the heart of European policymaking on medicines” and could weaken the independence and transparency of pharmaceutical product reviews. In an article published on 15th September in the British Medical Journal, McKee and Belcher believe the reshuffle represents “a victory of profits over public health”. These statements are of particular relevance to the rare disease community.

On 16th September, the EPHA issued a joint letter to Mr Juncker, co-signed by dozens of organisations, voicing their deep concern regarding the redistribution of Commission portfolios. The signatories demand that Mr Juncker “reconsider this decision” and state that “medicinal products and health technology belong under the responsibility of the Commissioner for health”, since pharmaceutical products cannot be evaluated as normal consumer goods. Organisations strongly regret not being consulted on this decision in a public debate and fear DG SANCO Commissioner Dr Vytenis Andriukaitis will no longer be able to fulfil DG SANCO’s mandate to promote and protect public health.

Read the European Commission press release
Read the EPHA press release
Read the EPHA joint letter
Consult the British Medical Journal article abstract


National & International Policy Developments
Guidance Documents and Recommendations
Anaplastic glioma and glioblastoma: European Association for Neuro-Oncology guideline for the diagnosis and treatment
Consult the Pubmed abstract
To read more about "Glial tumor"
To read more about "Glioblastoma"

Lancet Oncol. ; 15(9):e395-403 ; August 2014
Waldenström macroglobulinemia and related disorders: treatment recommendations from IWWM-7
Consult the Pubmed abstract
To read more about "Waldenström macroglobulinemia"

Blood ; 124(9):1404-1411 ; August 2014
Homozygous familial hypercholesterolemia: guidance to improve detection and clinical management
Consult the Pubmed abstract
To read more about "Homozygous familial hypercholesterolemia"

Eur Heart J. ; 35(32):2146-2157 ; August 2014
Lyme disease: guideline recommendations
Consult the Pubmed abstract
To read more about "Lyme disease"

Expert Rev Anti Infect Ther. ; 12(9):1103-35 ; September 2014
Bioinformatics, Registries and Data Management

The value of patient registries and surveys to understand rare disease progression, health burden and treatment efficacy
Enzyme replacement therapy (ERT) was first approved in Europe and the United States in 2006 to treat patients with Pompe disease, a rare and progressive lysosomal storage disorder caused by acid α-glucosidase (GAA) enzyme deficiency. Untreated patients accumulate glycogen in skeletal, cardiac and smooth muscle tissues, resulting in organ and system failure.

The International Pompe Association (IPA) and Erasmus MC University Medical Centre began a ten-year longitudinal survey of Pompe patients in 2002, four years before ERT treatment became available. In an article published in the Journal of Inherited Metabolic Disease, van der Meijden et al. studied the results of the IPA/Erasmus MC Pompe international survey of 408 child and adult Pompe patients, its impact on understanding the natural course of the disease and the effect of ERT treatment on quality of life.

Based on annual questionnaires concerning individual medical history, symptoms, daily physical and social capacities, clinical care and treatment, the survey collected pre- and post-treatment evidence from patients with a wide range of disease severity, and symptom- and age-onset. Results illustrate and quantify the changes in symptoms and quality of life in patients before and after treatment with ERT. Güngör et al. demonstrated the beneficial effects of ERT on Pompe patients from this survey in an article published last year in Orphanet Journal of Rare Diseases.

Van der Meijden et al. believe the Pompe survey serves as a model to measure the natural history of other untreated rare diseases in larger patient populations. Such evidence contributes towards therapeutic research and development, and measures the impact of new treatments on disease progression. Patient-reported outcomes further add to the volume of clinical evidence. The authors suggest self-reported symptoms and impairments help assess disease burden on daily and social life.

Consult the PubMed abstract

Dynamic, comprehensive, harmonised and connected: optimising bioinformatic tools to translate data into therapeutic development for rare diseases
Progress and innovation in rare disease (RD) treatment relies increasingly on advances in bioinformatics and international coordination of RD registries and biobanks. In an article published in Health Policy and Technology, Bellgard et al. identify a further seven components they believe must be standardised and harmonised to translate research on RDs into therapeutic opportunities: patient-practitioner partnerships, genomics platforms, population-wide studies, industry partnerships, personalised treatment, electronic health records and regulation.

Past initiatives began efforts to harmonise patient data and bioresources. In 2010, the NIH Office of Rare Disease Research (ORDR) launched a pilot project to harmonise patient registries and data sets internationally. The Global Rare Diseases Patient Registry and Data Repository (GRDR) programme aims to centralise coded patient records into a global web-based database, available to researchers working on RDs. In November 2012, the European Organisation for Rare Diseases (EURORDIS), the National Organisation for Rare Disorders (NORD) and the Canadian Organisation for Rare Disorders (CORD) issued a Joint Declaration on ten Key Principles for Rare Disease Patient Registries. The principles highlight the need to standardise patient data sets to support research, therapeutic development, health policy planning and drug surveillance in RDs. In January 2013, the European Union’s Seventh Framework Programme funded RD-Connect to link RD data sources.

Bellgard et al. propose building on these initiatives to rationalise data collection activities. As RD registries expand internationally, the authors highlight the need to further develop common RD data elements and clinical data management systems to capture patient records dynamically. Practitioners, academia and the industry must respect international standards of common data elements and ontology, i.e. disease classification, to ensure accuracy of data used in research, disease natural history studies, population-wide studies, diagnostics and tailored medicine. The authors believe harmonising registries and new technologies will facilitate collaboration between academia, industry, patient advocates and regulators. Such partnerships would attract increased funding and expertise on RDs, resulting in speedier therapeutic development.

Consult the abstract

Building European Reference Networks for rare diseases will require ongoing efforts to coordinate resources and data
In January 2012, EU Commission members and Member States began defining criteria to develop European Reference Networks (ERNs) for rare diseases (RDs), in response to Article 12 of European Directive 2011/24/EU on patients’ rights to cross-border healthcare. In an article published earlier this year in Nephrology Dialysis Transplantation, and as a reminder of the purpose of ERNs, Parker highlights the EUCERD’s recommendations on setting up RD ERNs, aimed at providing patients with comprehensive healthcare through centres of expertise.

RD ERNs must build on and coordinate mature networks of experts and patient registries in order to share medical resources and existing data. Parker highlights the importance of dialogue between experts (tele-expertise) in different locations and from different professional areas to avoid duplicating patient diagnoses and to improve patient management. Since funding reference networks for each of the 7,000 or so RDs is unsustainable, RD ERNs will cover disease clusters, requiring multidisciplinary expertise.

Collecting data into registries is essential to building RD ERNs. Orphanet lists over 600 European RD registries. While a number of regional or national registries contribute to European and international databases, Parker believes that many still operate alone. As mentioned in the previous article, registries, biobanks and RD databases must be harmonised and coordinated if datasets are to be exploited across different countries and rare diseases. IRDiRC and EUCERD have developed guidelines and tools to share resources and optimise use of data. Ongoing efforts to share resources and streamline data will be necessary to accomplish the RD ERNs objectives.

Consult the abstract

Launch of the Mitochondrial Disease Community Registry to advance research, diagnosis and treatment of mitochondrial diseases
On 18th August, the United Mitochondrial Disease Foundation (UMDF) announced the launch of the Mitochondrial Disease Community Registry (MDCR). The registry will collect information on mitochondrial disease from patients, caregivers and families in order to share data and advance research on currently untreated mitochondrial disorders. Onset of mitochondrial disease occurs primarily in children, but adult onset is becoming more frequent. While patients suffer progressive organ failure, diagnostic confirmation of the disease is still challenging. The MDCR aims to enhance research on symptoms to improve diagnosis and therapeutic development.

For further information

Methods of overcoming the challenges of small patient populations in clinical trials on rare diseases
Clinical trials on rare diseases are typically difficult to conduct due to limited patient numbers. In an article published in Expert Opinion on Orphan Drugs, O’Connor et al. identify several challenges associated with small patient pools. Researchers may find themselves competing for patients identified by several investigators. They must therefore be capable of identifying patients internationally and coordinate multiple clinical trial sites, whilst protecting patient identity. To optimise clinical trials on small patient numbers, investigators must consider the choice of trial design and methodology to gain significant results, depending on rare diseases and patient profiles. Insufficient understanding of rare diseases may impact trial outcomes, resulting in variable and inconclusive results.

O’Connor et al. suggest investigators increase patient participation through collaboration with international patient associations and expert centres. Researchers should provide education to engage participants actively and increase their interest in trial design and process. The authors suggest that predicting patient drop-out and subsequent loss of data would allow investigators to design trials adequately and maximise patient input. Various study designs have been developed to address small patient numbers. Adaptive trials allow investigators to modify aspects of the study as it progresses, obtain intermediate results and integrate results into subsequent trial phases. Bayesian methods enable investigators to make assumptions and define endpoints based on accumulated data.

Regulators recognise the challenges of designing clinical trials for small patient numbers and have consequently developed flexible evaluation frameworks. Conditional marketing authorisation and adaptive licensing offer sponsors the possibility to market orphan drugs, provided they continue collecting ongoing clinical and post-marketing evidence on drug safety and efficacy. O’Connor et al. highlight recent efforts to promote clinical research on rare diseases in small populations: EU-funded projects IDEAL, InSPiRe, ASTERIX and CAVOD aim to develop innovative approaches to adapt and assess clinical trials on small populations and rare diseases.

Consult the abstract

Screening and Testing

Progress in diagnosing skeletal dysplasia in a southern Indian hospital could serve as a model for other rare diseases and for developing countries
In India, genetic testing is available in cities but rarely in rural settings. In an article published in the American Journal of Medical Genetics, Nampoothiri et al. report the experience of skeletal dysplasia (SD) diagnosis in a hospital in Kerala, where half the population lives in rural areas. From November 2005 to April 2013, physicians were trained to conduct genetic counselling, evaluation and testing on families at risk of carrying some form of SD or related condition. With the remote assistance of specialists based abroad, for complex cases, and networks such as the European Skeletal Dysplasia Network, the hospital investigators diagnosed 514 cases of SD. Mutation analysis confirmed 109 cases, 54 cases were confirmed by enzyme analysis and the remaining 351 were diagnosed by clinical and radiological evaluation.

The authors believe this experience demonstrates how international collaborative efforts contribute significantly to progress in diagnosing rare conditions in otherwise remote areas. They emphasise the importance of thorough clinical evaluation to document prognosis, choose appropriate tests and validate diagnosis of SD conditions. Such rigorous clinical pre-selection allowed investigators to identify and characterise a number of rare conditions and enrol patients into international research projects. While only 514 patients were diagnosed, out of the estimated 100,000 individuals living with SD in India, the authors suggest this experience could serve as a model to improve diagnosis of rare diseases in the rest of India and in developing countries.

Read the open access article

Most parents in Japan choose to terminate pregnancy following diagnosis of chromosomal abnormality
To date, the Japanese Society of Obstetrics and Gynaecology (JSOG) has made no recommendations concerning prenatal diagnostic testing. Consequently, prenatal screening is performed in only 3% of pregnant women. Fewer still receive genetic counselling from an obstetrician. In an article published in the Journal of Genetic Counseling, Suzumori et al. aim to assess the level of understanding and acceptance of prenatal diagnosis in the Japanese population and its consequences on pregnancy termination choices.

In Japan, where disabilities are widely unaccepted by society, the authors discovered that most parents opt to terminate pregnancy when their foetus is diagnosed with chromosomal abnormalities, following prenatal test results. While the majority of pregnant women wish to know whether their foetus is at risk of chromosomal abnormality, those who undergo prenatal screening tests rarely receive genetic counselling. Suzumori et al. emphasise the need in Japan to educate and train health professionals in genetic counselling to accompany parents in their decisions following genetic screening. They also highlight the need to educate the wider society to provide for mental and physical disabilities.

Consult the PubMed abstract

Non-invasive prenatal testing in the Dutch national screening programme
In an article published in the European Journal of Obstetrics and Gynecology and Reproductive Biology, Beulen et al. anticipate the health and economic consequences of introducing non-invasive prenatal testing (NIPT) into the Dutch national screening programme. NIPT has been demonstrated to detect foetal aneuploidy accurately, namely trisomy 21 (T21), in high- and average-risk pregnant women. The authors base their assumptions on a pilot launch of NIPT, initiated in April 2014.

The authors believe that applying NIPT as the principal screening test for T21 would be the most effective option. They project that T21 detection rates could increase as much as 54% if NIPT were used alone. If NIPT is used as an optional secondary screening test to support first-trimester and combined invasive screening, Beulen et al. anticipate T21 detection rates to increase by 36%. The authors believe that introducing NIPT would contribute significantly to reduce the practice of invasive diagnostic testing and resulting risks of miscarriage.

While NIPT is the most effective screening method, it is also the most expensive. The authors calculated that adopting NIPT as the primary screening test would increase the screening programme cost by 157%, whereas introducing NIPT as an optional secondary test would push the cost up 21%. NIPT as principal screening choice is therefore only feasible if the cost of this technique decreases significantly. The authors nevertheless believe that NIPT should be considered as an option to improve detection of T21 and increase parent choices early on.

Consult the abstract


Ethical, Legal & Social Issues

The need to consider the full economic burden of rare diseases in health policy planning: a study of costs associated with caring for patients with Duchenne muscular dystrophy
Patients with Duchenne muscular dystrophy (DMD) lose muscle function early on during childhood. They are usually wheelchair bound by their early teens and suffer cardiac and respiratory complications by early adulthood. In an article published in Neurology, Landfeldt et al. estimate the economic burden of DMD on society and patient households, based on a 2012 investigation of DMD patients in Germany, Italy, the UK and the US.

Direct costs of disease, resulting from patients’ use of medical and non-medical resources, reached just over US$ 54,000 in the US and UK, more than twice the annual per-patient cost in Italy. The authors estimated indirect and intangible costs—resulting from caregivers’ reduced capacity to work whilst caring for a patient and reduced quality of life— to be greater than direct costs in all four countries, at around
US$ 64,000 per patient per year. The estimated total social burden of DMD ranged from US$ 80,120 (Italy) to US$ 120,910 (US). Further household expenditure, such as out-of-pocket payments and costs associated with adapting a home for wheelchair access for instance, were estimated at US$ 66,000 on average per household annually.

Landfeldt et al.’s study reveals that the overall economic burden of DMD may be generally under estimated as a number of criteria, including income loss, reduced quality of life for patients and their families, out-of-pocket payments and costs associated with end-of-life care and mortality, are not systematically incorporated into calculations. The authors recommend that all costs associated with long term patient care be integrated into health planning for rare disease management in order to better allocate funds and adequately support families caring for patients with rare diseases.

Read the open access article

Methods and consequences of engaging patients in research on rare diseases
The research community has, over the years, increased efforts to involve patients with rare diseases in decisions concerning clinical investigations and treatment choices. In a systematic review of the literature, published in the Journal of General Internal Medicine, Forsythe et al. assess the degree of patient, caregiver and patient organisation engagement in research processes. The authors conducted their review based on five considerations: the purpose of engaging patients in clinical research; the methods of identification and engagement; the effects of involving patients in research; the role of patient organisations in patient identification and recruitment; and the challenges of engaging patients in research on rare diseases.

The authors’ findings indicate that patients are engaged, usually, during clinical study preparation and execution phases. They are recruited through patient organisations, clinics, agencies and online. In several cases, investigators engage patients to guide decisions on study topic, design and outcomes assessment. In addition to providing investigators with patient contacts, patient organisations often support collaborative research and patient engagement in clinical investigations. Finally, while researchers support patient involvement, engagement is time and resource intensive.

While the number of studies reporting patient engagement is limited, Forsythe et al. believe collaboration between research communities, patients and organisations would enhance patient health outcomes in clinical investigations. The authors highlight the important role of patient organisations in facilitating contact between stakeholders, identifying research opportunities, and providing financial support and training. They suggest guidelines on methods of identifying and recruiting patients would benefit stakeholders. They believe initiatives such as the Patient-Centered Outcomes Research Institute (PCORI), to support and evaluate the impact of patient engagement on health outcomes, may improve collaborative research on rare diseases.

Read the open access article


New Syndromes

Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum–like skin manifestations associated with GGCX homozygous mutations in 13 members of 2 families
The authors reported on the clinical findings and molecular results in 13 affected members of two families who had uniform phenotype consisting of pseudoxanthoma elasticum-like skin manifestations in the neck and trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa confirmed by electroretinographies in 10 affected individuals. There were no coagulation abnormalities. All 13 affected family members presented a homozygous splice-site mutation in the GGCX gene.
Consult the Pubmed abstract

J Invest Dermatol. ; 134(9):2331-8 ; September 2014
Autosomal-recessive ectodermal dysplasia syndrome caused by mutations in GRHL2 in two unrelated consanguineous families
The authors investigated two unrelated consanguineous Kuwaiti families in which a total of six individuals have had lifelong ectodermal defects. The clinical features comprised nail dystrophy or nail loss, marginal palmoplantar keratoderma, hypodontia, enamel hypoplasia, oral hyperpigmentation, and dysphagia. In addition, three individuals had sensorineural deafness, and three had bronchial asthma. Taken together, the features were consistent with an unusual autosomal-recessive ectodermal dysplasia syndrome. GRHL2 mutations were found in both families.
Consult the Pubmed abstract

Am J Hum Genet. ; 95(3):308-14 ; September 2014
Cavitating leukoencephalopathy with cytochrome c oxidase deficiency linked to recessive mutations in APOPT1 in six subjects
Whole-exome sequencing led to the identification of APOPT1 mutations in two Italian sisters and in a third Turkish individual presenting severe cytochrome c oxidase deficiency. All three subjects presented a distinctive brain MRI pattern characterized by cavitating leukodystrophy, predominantly in the posterior region of the cerebral hemispheres. The authors then found APOPT1 mutations in three additional unrelated children, selected on the basis of these particular MRI features.
Consult the Pubmed abstract

Am J Hum Genet. ; 95(3):315-25 ; September 2014
Autosomal-dominant form of Lambert-Eaton myasthenic syndrome and non-progressive motor neuropathy associated with SYT2 mutations
The authors identified heterozygous missense mutations in the C2B calcium-binding domain of SYT2 in two multigenerational families presenting with peripheral motor neuron syndromes. Mutations in the SYT2 C2B domain represent an important cause of disorders of the human peripheral motor nerve terminal; foot deformities are a hallmark, with phenotypes ranging from a dominant neuromuscular junction syndrome resembling Lambert-Eaton myasthenic syndrome to mixed manifestations of distal hereditary motor neuropathy and presynaptic neuromuscular junction dysfunction.
Consult the Pubmed abstract

Am J Hum Genet. ; 95(3):332-9 ; September 2014
Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from missense mutations in TTC7A
The authors performed genetic linkage analysis and candidate gene sequencing on 13 patients from a large consanguineous family and in an unrelated patient presenting with immune deficiency-related enteropathy-lymphocytopenia-alopecia (ELA) syndrome. Biallelic missense mutations were identified in TTC7A in all patients.
Consult the Pubmed abstract

J Allergy Clin Immunol. ; [Epub ahead of print] ; August 2014

New Genes

Congenital myasthenic syndrome with distal muscle weakness and atrophy due to agrin recessive mutations in five patients from three unrelated families
Consult the Pubmed abstract
Brain ; 137(Pt 9):2429-43 ; September 2014
Primary ciliary dyskinesia caused by CCDC151 loss-of-function mutations in five affected individuals from three independent families
Consult the Pubmed abstract
To read more about "Primary ciliary dyskinesia"

Am J Hum Genet. ; 95(3):257-74 ; September 2014
Adams-Oliver syndrome due to heterozygous mutations in NOTCH1 in unrelated individuals
Consult the Pubmed abstract
To read more about "Adams-Oliver syndrome"

Am J Hum Genet. ; 95(3):275-84 ; September 2014
Neu-Laxova syndrome linked to three different missense and frameshift PSAT1 mutations in six families, and to a homozygous frameshift mutation in PSPH in one family
Consult the Pubmed abstract
To read more about "Neu-Laxova syndrome"

Am J Hum Genet. ; 95(3):285-93 ; September 2014
Recessive axonal or mixed form of Charcot-Marie-Tooth disease caused by a mutation in COX6A1
Consult the Pubmed abstract
To read more about "Charcot-Marie-Tooth disease"

Am J Hum Genet. ; 95(3):294-300 ; September 2014
Autosomal dominant Charcot-Marie-Tooth disease type 2 associated to a novel mutation in TFG in a large Taiwanese family
Consult the Pubmed abstract
To read more about "Autosomal dominant Charcot-Marie-Tooth disease type 2"

Neurology ; 83(10):903-12 ; September 2014
Kallmann syndrome linked to loss-of-function mutations in FEZF1 in two independent consanguineous families each with two affected siblings
Consult the Pubmed abstract
To read more about "Kallmann syndrome"

Am J Hum Genet. ; 95(3):326-31 ; September 2014
Severe congenital neutropenia associated with homozygous mutations in JAGN1 in 14 individuals
Consult the Pubmed abstract
To read more about "Severe congenital neutropenia"

Nat Genet. ; 46(9):1021-7 ; September 2014
Predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency due to germline mutation of RPS20 in a family
Consult the Pubmed abstract
To read more about "Hereditary nonpolyposis colon cancer"

Gastroenterology ; 147(3):595-598.e5 ; September 2014
Familial glucocorticoid deficiency associated with a stop gain mutation in TXNRD2 in a Kashmiri kindred
Consult the Pubmed abstract
To read more about "Familial glucocorticoid deficiency"

J Clin Endocrinol Metab. ; 99(8):E1556-63 ; August 2014
Involvement of TNFRSF11A molecular defects in hereditary periodic fever syndrome exhibiting clinical similarities to TRAPS syndrome
Consult the Pubmed abstract
Arthritis Rheumatol. ; 66(9):2621-7 ; September 2014
Congenital, generalized lipodystrophy similar to Berardinelli-Seip syndrome caused by biallelic mutations in PPARG in one individual
Consult the Pubmed abstract
To read more about "Berardinelli-Seip congenital lipodystrophy"

Eur J Med Genet. ; 57(9):524-6 ; September 2014
Impetigo herpetiformis found associated with homozygous and heterozygous IL36RN mutations
Consult the Pubmed abstract
J Invest Dermatol. ; 134(9):2472-4 ; September 2014
Mutations in ALMS1 cause the lethal disorder mitogenic cardiomyopathy
Consult the Pubmed abstracts
Nat Commun. ; 5:3416 ; March 2014
Eur J Med Genet. ; 57(9):532-5 ; September 2014
Germline and somatic DICER1 mutations in pituitary blastoma causing infantile-onset Cushing’s syndrome
Consult the Pubmed abstracts
Acta Neuropathol. ; 128(1):111-22 ; July 2014
J Clin Endocrinol Metab. ; 99(8):E1487-92 ; August 2014
Developmental disorder of the pancreas linked to GATA4 mutation or deletions in 5 patients
Consult the Pubmed abstract
Diabetes ; 63(8):2888-94 ; August 2014
Pollitt syndrome patients carry a homozygous single-base pair deletion in TTDN1
Consult the article
To read more about "Pollitt syndrome"

Meta Gene ; 2:616-618 ; December 2014
Short stature, accelerated bone maturation, and early growth cessation due to heterozygous variants in ACAN in three families
Consult the Pubmed abstract
J Clin Endocrinol Metab. ; 99(8):E1510-8 ; August 2014
Macrophage activation syndrome: novel cytolytic pathway gene mutations identified in children
Consult the Pubmed abstract
To read more about "Macrophage activation syndrome"

Curr Rheumatol Rep. ; 16(9):439 ; September 2014
Heterozygous variants in components of the NOX2 NADPH oxidase complex associated with susceptibility to very early onset inflammatory bowel disease
Consult the Pubmed abstract
Gastroenterology ; 147(3):680-689.e2 ; September 2014

Research in Action

Clinical Research
Glioblastoma: the combination of bevacizumab and lomustine met pre-specified criteria for assessment of this treatment in further phase 3 studies
Consult the Pubmed abstract
To read more about "Glioblastoma"

Lancet Oncol. ; 15(9):943-53 ; August 2014
Glioblastoma: the addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes
Consult the Pubmed abstract

Consult this study on Orphanet
Consult this study on Orphanet
Consult this study on Orphanet

To read more about "Glioblastoma"

Lancet Oncol. ; 15(10):1100-8 ; September 2014
Multicentric Castleman disease: siltuximab plus best supportive care was superior to best supportive care alone
Consult the Pubmed abstract

To read more about "Multicentric Castleman disease"

Lancet Oncol. ; 15(9):966-74 ; August 2014
Primary sclerosing cholangitis: interruption of long-term treatment with ursodeoxycholic acid results in rapid significant deterioration of biochemical cholestasis
Consult the Pubmed abstract
To read more about "Primary sclerosing cholangitis"

Hepatology ; 60(3):931-40 ; September 2014
Systemic-onset juvenile idiopathic arthritis: rilonacept was well tolerated and showed efficacy in 71 children
Consult the Pubmed abstract
To read more about "Systemic-onset juvenile idiopathic arthritis"

Arthritis Rheumatol. ; 66(9):2570-9 ; September 2014
Juvenile idiopathic arthritis: a study on the German Biologics JIA Registry demonstrated efficacy and safety of adalimumab in 289 patients
Consult the Pubmed abstract
To read more about "Juvenile idiopathic arthritis"

Arthritis Rheumatol. ; 66(9):2580-9 ; September 2014
Granulomatosis with polyangiitis: rituximab is an effective treatment for ear, nose and throat disease manifestations
Consult the abstract
To read more about "Granulomatosis with polyangiitis"

Arthritis Care & Research ; 66(9):1403-1409 ; September 2014
Hypoplastic left heart syndrome: survival among patients who underwent fetal aortic valvuloplasty and achieved a biventricular circulation postnatally is encouraging
Consult the Pubmed abstract
To read more about "Hypoplastic left heart syndrome"

Circulation ; 130(8):638-45 ; August 2014
Bronchiolitis obliterans: methylprednisolone pulse therapy could be a safe alternative to prolonged systemic oral corticotherapy in children
Consult the Pubmed abstract
Orphanet J Rare Dis. ; 9:128 ; August 2014
Graft versus host disease: bortezomib provides therapeutic benefits
Consult the Pubmed abstract
To read more about "Graft versus host disease"

Blood ; 124(10):1677-88 ; September 2014
Short stature women with unexplained elevated liver enzymes frequently indicative of Turner syndrome caused by X chromosome abnormalities
Consult the Pubmed abstract
To read more about "Turner syndrome"

J Clin Endocrinol Metab. ; 99(8):E1592-6 ; August 2014
Gene Therapy
Duchenne muscular dystrophy: translation from a DMD exon 5 internal ribosome entry site results in a functional dystrophin isoform that attenuates the disease in humans and mice
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Nat Med. ; 20(9):992-1000 ; September 2014
Spinocerebellar ataxia type 7: non-allele specific silencing of ataxin-7 improves disease phenotypes in a mouse model
Consult the Pubmed abstract
To read more about "Spinocerebellar ataxia type 7"
To read more about "Autosomal dominant cerebellar ataxia"

Mol Ther. ; 22(9):1635-42 ; September 2014
Phenylketonuria: minicircle technology offers an improved safety profile and has the potential for the genetic treatment of liver diseases
Consult the Pubmed abstract
To read more about "Phenylketonuria"

Hepatology ; 60(3):1035-43 ; September 2014
Therapeutic Approaches

Charcot-Marie-Tooth disease type 1A: soluble neuregulin-1 modulates disease pathogenesis in rat models
Consult the Pubmed abstract
To read more about "Charcot-Marie-Tooth disease type 1A"

Nat Med. ; 20(9):1055-61 ; September 2014
Echinomycin protects mice against relapsed acute myeloid leukemia without adverse effect on hematopoietic stem cells
Consult the Pubmed abstract
To read more about "Acute myeloid leukemia"

Blood ; 124(7):1127-35 ; August 2014
Chronic myeloid leukemia: combined treatment with imatinib mesylate and trametinib prolongs survival in mouse models
Consult the Pubmed abstract
To read more about "Chronic myeloid leukemia"

Sci Transl Med. ; 6(252):252ra121 ; September 2014
Small cell carcinoma of the ovary: anti-tumorigenic effects of epothilone B / Ca2+ in mice
Consult the Pubmed abstract
To read more about "Small cell carcinoma of the ovary"

Orphanet J Rare Dis. ; 9:126 ; August 2014
Pulmonary arterial hypertension: apolipoprotein A-I mimetic peptide 4F rescues pulmonary hypertension in rat and mouse models
Consult the Pubmed abstract
To read more about "Pulmonary arterial hypertension"

Circulation ; 130(9):776-85 ; August 2014
Pulmonary arterial hypertension: CCR5, a co-receptor for cellular HIV-1 entry expressed on macrophages and vascular cells, as a treatment target
Consult the Pubmed abstract
To read more about "Pulmonary arterial hypertension"

Circulation ; 130(11):880-91 ; September 2014
Haemophilia A: oral delivery of plant cells expressing FVIII domains suppresses and reverses inhibitor formation in mice
Consult the Pubmed abstract
To read more about "Hemophilia A"

Blood ; 124(10):1659-68 ; September 2014
Duchenne muscular dystrophy: exon skipping restores dystrophin expression, but fails to prevent disease progression in later stage dystrophic dko mice
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Gene Ther. ; 21(9):785-93 ; September 2014
Diagnostic Approaches

Next-generation sequencing of the disease-associated genome followed by phenotype-driven bioinformatic analysis allows quick and effective differential diagnostics
Consult the Pubmed abstract
To read more about "Creutzfeldt-Jakob disease"

Sci Transl Med. ; 6(252):252ra123 ; September 2014
Ehlers-Danlos syndrome: how to diagnose and when to perform genetic tests
Consult the Pubmed abstract
To read more about "Ehlers-Danlos syndrome"

Arch Dis Child. ; [Epub ahead of print] ; July 2014
Niemann-Pick disease type C: genetic and laboratory diagnostic approach
Consult the Pubmed abstract
To read more about "Niemann-Pick disease type C"

J Neurol. ; 261 Suppl 2:569-75 ; September 2014
Improved diagnosis of idiopathic giant cell myocarditis and cardiac sarcoidosis by myocardial gene expression profiling
Consult the Pubmed abstract
To read more about "Young adult-onset distal hereditary motor neuropathy"
To read more about "Sarcoidosis"

Eur Heart J. ; 35(32):2186-95 ; August 2014
Secondary hemophagocytic lymphohistiocytosis: the HScore can be used to estimate an individual’s risk of having the disease
Consult the Pubmed abstract
To read more about "Secondary hemophagocytic lymphohistiocytosis"

Arthritis Rheumatol. ; 66(9):2613-20 ; September 2014
Cholangiocarcinoma: human bile contains microRNA-laden extracellular vesicles that can be used for diagnosis
Consult the Pubmed abstract
To read more about "Cholangiocarcinoma"

Hepatology ; 60(3):896-907 ; September 2014
A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir–Torre variant of Lynch syndrome
Consult the Pubmed abstract
To read more about "Muir-Torre syndrome"

Genet Med. ; 16(9):711-6 ; September 2014
Facioscapulohumeral dystrophy: assays for hypomethylation within the D4Z4 region distinguish patients with the disease from individuals with D4Z4 contraction without the disease
Consult the Pubmed abstract
To read more about "Facioscapulohumeral dystrophy"

Neurology ; 83(8):733-42 ; August 2014
Mucopolysaccharidosis: a modified liquid chromatography/tandem mass spectrometry method can help to make correct diagnosis and evaluate the efficacy of enzyme replacement therapy
Consult the Pubmed abstract
To read more about "Mucopolysaccharidosis type 1"
To read more about "Mucopolysaccharidosis type 2"
To read more about "Mucopolysaccharidosis type 3"
To read more about "Mucopolysaccharidosis type 6"

Orphanet J Rare Dis. ; 9:135 ; September 2014

Patient Management and Therapy
Congenital diaphragmatic hernia: a clinical prediction rule for the severity of the disease in newborns
Consult the Pubmed abstract
To read more about "Congenital diaphragmatic hernia"

Pediatrics ; 134(2):e413-9 ; August 2014
Comprehensive evaluation of the child with intellectual disability
Consult the Pubmed abstract
Pediatrics ; 134(3):e903-18 ; September 2014
Porphyria: review on diagnostic approaches, management strategies and recommendation for liver transplantation
Consult the Pubmed abstract
To read more about "Porphyria"

Hepatology ; 60(3):1082-9 ; September 2014
Autoimmune lymphoproliferative syndrome: splenectomy should be avoided as patients are predisposed to invasive bacterial infections
Consult the Pubmed abstract
To read more about "Autoimmune lymphoproliferative syndrome"

Blood ; 124(10):1597-609 ; September 2014
Primary immunodeficiency: reviews on prevention of infections and on inborn errors of metabolism
Consult the Pubmed abstracts
To read more about "Primary immunodeficiency"

Clin Infect Dis. ; [Epub ahead of print] ; August 2014
J Clin Immunol. ; 34(7):753-71 ; October 2014
Immunodeficiency by defective expression of HLA class 1 and 2: a review
Consult the abstract
To read more about "Immunodeficiency by defective expression of HLA class 1"
To read more about "Immunodeficiency by defective expression of HLA class 2"

J Allergy Clin Immunol. ; 134(2):269-75 ; August 2014
Batten disease: review on screening, diagnosis and epidemiology
Consult the abstract
To read more about "Juvenile neuronal ceroid lipofuscinosis"
To read more about "Late infantile neuronal ceroid lipofuscinosis"
To read more about "Infantile neuronal ceroid lipofuscinosis"

Expert Opinion on Orphan Drugs ; 2(9):903-910 ; September 2014
Phosphodiesterase type 5 inhibitors for stuttering priapism: review on recent advances
Consult the abstract
Expert Opinion on Orphan Drugs ; 2(9):937-946 ; September 2014
Acute promyelocytic leukemia: review on tamibarotene treatment
Consult the abstract
To read more about "Acute promyelocytic leukemia"

Expert Opinion on Orphan Drugs ; 2(9):961-969 ; September 2014
Ataxia-telangiectasia: review on current and future therapeutic strategies
Consult the abstract
To read more about "Ataxia-telangiectasia"

Expert Opinion on Orphan Drugs ; 2(9):877-887 ; September 2014
Sézary syndrome: overview of current and future treatment options
Consult the abstract
To read more about "Sézary syndrome"

Expert Opinion on Orphan Drugs ; 2(9):889-901 ; September 2014
Adrenocortical carcinoma: review on treatment
Consult the abstract
To read more about "Adrenocortical carcinoma"

Expert Opinion on Orphan Drugs ; 2(9):911-921 ; September 2014
Japanese encephalitis: review on epidemiology, prevention and current status of antiviral drug development
Consult the abstract
To read more about "Japanese encephalitis"

Expert Opinion on Orphan Drugs ; 2(9):923-936 ; September 2014
Schnitzler syndrome: review on the management
Consult the abstract
To read more about "Schnitzler syndrome"

Expert Opinion on Orphan Drugs ; 2(9):947-955 ; September 2014
Autosomal recessive polycystic kidney disease: a review
Consult the Pubmed abstract
To read more about "Autosomal recessive polycystic kidney disease"

Pediatrics ; 134(3):e833-e845 ; August 2014
Pemphigoid gestationis : a review
Consult the Pubmed abstract
To read more about "Pemphigoid gestationis"

Orphanet J Rare Dis. ; 9(1):136 ; September 2014
Raine syndrome: an overview
Consult the Pubmed abstract
To read more about "Lethal osteosclerotic bone dysplasia"

Eur J Med Genet. ; 57(9):536-542 ; September 2014
Trilateral retinoblastoma: a systematic review and meta-analysis
Consult the Pubmed abstract
To read more about "Retinoblastoma"

Lancet Oncol. ; 15(10):1157-67 ; September 2014
Composite lymphomas: review on pathogenesis, diagnosis, and treatment
Lire le résumé
Lancet Oncol. ; 15(10):e435-e446 ; September 2014
Lyme disease: a review
Consult the Pubmed abstract
To read more about "Lyme disease"

Arthritis Rheumatol. ; 66(9):2313-23 ; September 2014
Pachydermodactyly: a review
Consult the Pubmed abstract
Curr Rheumatol Rep. ; 16(9):442 ; September 2014
Special issue of the European Journal of Medical Genetics on genetics of common malformations
Consult the special issue
European Journal of Medical Genetics ; 57(8):353-486 ; August 2014
Two new and two updated Clinical Utility Gene Cards published in the European Journal of Human Genetics
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 two new Clinical Utility Gene Cards for:
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis with/without severe ocular involvement Lowe syndrome

The European Journal of Human Genetics has published two updated Clinical Utility Gene Cards for:
Dyskeratosis congenita Werner syndrome

Four updated GeneReviews published
GeneReviews are expert-authored, peer-reviewed disease descriptions ("chapters") presented in a standardized format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions. Four updated GeneReviews have been published for:
Neurofibromatosis Arginase deficiency Autosomal recessive congenital ichthyosis X-linked juvenile retinoschisis


Orphan Drugs

Regulatory News
New regulatory measures in France for temporary authorisation uses (ATUs), so-called cohort ATUs and named patient ATUs

The French national medicines agency (ANSM) issues ‘Temporary Authorisations for Use’ (ATU) as exceptional measures to provide medicinal products, which have not received marketing authorisation, to treat serious or rare diseases. An ATU is granted to provide early access to a drug when no other appropriate treatment exists and where there is a legitimate health need, in accordance with Article L5121-12 of the French Public Health Code.

A ‘Protocol for Therapeutic Use and Information Collection’ (PUT) is drawn up between the ANSM and the licence holder in order to provide healthcare professionals with information concerning the medicinal product under temporary use. The PUT is established to monitor treated patients and collect data concerning efficacy, side effects, real-life conditions of use and the profiles of treated patients.

The use of medicinal products benefitting from an ATU does not replace a clinical trial and must not be investigative in nature. Clinical trials must continue to be conducted to provide essential data and benefit/risk evidence at this early stage of drug development.

For further information in French
For further information in English

Political and Scientific News
Pricing and reimbursement policies on orphan medicinal products in Turkey
While no formal orphan drug legislation exists in Turkey, a working group was constituted to establish pricing and reimbursement policies on orphan drugs to facilitate patients’ access to medicines for rare diseases. In an article published in Value in Health Regional Issues, Koçkaya et al. describe the Turkish orphan drug landscape. The Turkish Medicines and Medical Device Agency, Türkiye İlaç ve Tıbbi Cihaz Kurumu (TITCK), governs pharmaceutical product pricing, based on European country reference prices. The Social Security Institution, Sosyal Güvenlik Kurumu (SGK), decides on drug reimbursement.

Two commissions were constituted, composed of the TITCK, the SGK and the Ministry of Finance, to decide on orphan medicinal product access and reimbursement. The Medical and Economic Evaluation Commission assesses orphan drug applications and the Reimbursement Commission makes final decisions. While ordinary drug applications require a pharmacoeconomic analysis, orphan drugs do not and therefore enter the Turkish market relatively quickly. The TITCK sets orphan drug prices and the SGK reviews them annually, based on sales volumes. All evaluated orphan drugs are fully reimbursed, whether approved for on-label use or unlicensed and used off-label.

In 2010, 18 authorised orphan drugs and 17 unlicensed orphan drugs were available in Turkey. While authorised orphan drug prices decreased 22% between 2008 and 2010, due to changes in reference pricing and reimbursement discounts, non-authorised orphan drug prices increased. The Turkish orphan drug market value rose 40% during the same period and units consumed increased 82%, suggesting a greater consumption of authorised orphan drugs. The authors suggest that analysing the orphan drug evaluation process in Turkey could serve to understand pricing and reimbursement policy variations for orphan drugs in other countries.

Consult the abstract

Comparing computer generated molecular structures to support the evaluation of new orphan drugs: a strong case for 2D fingerprint methods

Once authorised by the European Commission, orphan drugs are granted a ten year exclusivity period in Europe, during which time no similar drug can be marketed. Commission Regulation (EC) No 847/2000 of 27 April 2000 provides definitions of drug similarity and superiority to support implementation of Articles 3 and 8 of Regulation (EC) No 141/2000 of 16 December 1999 on orphan medicinal products concerning orphan drug similarity. Article 3, on criteria for designation, states that “a medicinal product shall be designated as an orphan medicinal product if its sponsor can establish (...) that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Community.” Article 8, concerning market exclusivity, states that “a marketing authorisation may be granted, for the same therapeutic indication, to a similar medicinal product if (...) the second applicant can establish in the application that the second medicinal product, although similar to the orphan medicinal product already authorised, is safer, more effective or otherwise clinically superior.”

In an article published in the Journal of Chemoinformatics, Franco et al. investigate the use of 2D fingerprints to support and confirm the decisions of the EMA’s Committee for Medicinal Products for Human Use (CHMP) on orphan drug authorisations. When molecular similarities or dissimilarities between orphan products are not evident to the human eye, Franco et al. illustrate how computer models are capable of assessing molecular resemblance or differences between two compounds by comparing fingerprints, i.e. binary codes representing molecular structural features. While the authors by no means suggest replacing CHMP experts on decisions concerning orphan drug evaluation, they do believe 2D fingerprints, and potentially 3D structural information, are effective tools to compare molecular structures. Franco et al. suggest 2D fingerprinting is a useful method to corroborate CHMP expert panel decisions on applications for orphan drug authorisation.

Read the open access article



FRT - Fondation René Touraine (FRT) Award
These grants are awarded to encourage exchanges and international collaboration between research laboratories or clinical departments for pre- or post-doctoral research fellows and dermatologists. The award consists of one €18,000 fellowship for a long-term exchange and four €4,500 fellowships for a short-term exchanges. Eligibility criteria for these grants includes: exchange with a laboratory or department from another country; involvement of at least one European laboratory; benefits for both host and home laboratories.
Application deadline: 1 October, 2014.
Download the application form
For further details

7th international Call for SMA Research Projects
This Call is open to any research project aimed at finding a therapy for Spinal Muscular Atrophy (SMA) or elucidating the basic pathophysiological processes of the disease. SMA-Europe aims to help the international scientific and medical community in its search for therapies for SMA. Preferences will be given to projects with the greatest potential to overcome barriers to translate science into effective treatments.
Two types of research grants will be awarded for up to two years:
1. Operating Grants
2. Postdoctoral Fellowship
Application deadline: 16 October, 2014
For further details


Courses & Educational Initiatives

‘Explique-moi les essais cliniques’: the keys to understanding clinical trials to become an actor of one’s disease (in French)
Date: 14-15 October 2014
Venue: Marseille, France

The objective of this course is to sensitise patients to clinical trials through better understanding of the drug development process, in particular the way in which clinical trials are conducted.
The course will be held in French.
For further information

Workshop: a common vocabulary to classify resources in the life science domain
Date: 16 October, 2014
Venue: Brussels, Belgium

A one day vocabulary workshop, organised by ELIXIR, BioMedBridges and RDA, to agree on common vocabulary to classify resources in the life sciences domain. The course welcomes representatives of societies, networks, institutes, organisations, research infrastructures and projects and will involve and welcome ontologists to participate in discussions.
For further information

Genodermatoses Network Training Session
Date: 30-31 October 2014
Venue: Paris, France

The objective of this course is to increase knowledge on cutis laxa, ectodermal and keratodermal disorders, their detection, diagnosis and management; develop and improve skills to manage common problems in different genodermatoses; encourage health care providers to adopt a multidisciplinary approach; provide updates on latest findings and treatments; highlight the key role of patient groups; and network specialists. This training is intended for all health care providers involved in the field of rare skin diseases.
For further information

III International EPIRARE workshop: rare disease and orphan drug registries
Date: 24-25 November, 2014
Venue: Rome, Italy

Participants will be able to exchange experiences and present scientific results, in an effort to foster international collaboration.
For further information

ESH-ENERCA Training course on haemoglobin disorders: laboratory diagnosis and clinical management
Date: 23-24 January, 2015
Venue: Barcelona, Spain

The course will cover the following topics: Epidemiology in practice, Clinical aspects of thalassaemia, Trends in biological aspects of thalassaemia, Abnormal haemoglobins and Complications and treatments of thalassaemia and sickle cell disease.
Participants are encouraged to submit clinical cases or abstracts for presentation and discussion during the meeting. Submit your detailed clinical case(s) online
Deadline for clinical cases and abstracts: 24 November, 2014
For further information


What's on Where?

EFGCP / DIA / EMA Annual Conference 2014 on Better Medicines for Children: ‘Explore Ways to Enhance Collaboration Between Key Players’
Date: 30 September - 1 October, 2014
Venue: London, UK

The aim of this conference is to discuss on a high level how the EU paediatric regulation is working and how it contributes to children’s health. This will include a discussion on the preparedness for the 10-year report, strategic thoughts within the EMA on how to streamline paediatric development and a session dedicated to paediatric oncology.
For further information

Single topic symposium in metabolic liver disease
Date: 2-4 October, 2014
Venue: Birmingham, UK

This symposium will include experts presenting information on diagnosis and treatment of metabolic liver disease as well as information on lipid disorders such as homozygous hypercholesterolaemia, Lysosomal acid lipase deficiency, Mitochondrial Diseases and other specific metabolic disorders.
For further information

Expanded carrier screening: possibilities and challenges
Date: 6 October, 2014
Venue: Leuven, Belgium

The symposium will explore the various population-based carrier screening performed for single-gene recessive disorders associated with significant morbidity and reduced life-expectancy. Examples are carrier screening for cystic fibrosis (CF) (offered in countries including the United States, Australia, Italy, Israel) and ß-thalassemia (offered in e.g. Cyprus, Sardinia, Israel). Other examples include limited panels of disorders aimed at specific communities such as the Ashkenazi Jewish population, which have dramatically lowered the number of children affected with diseases such as Tay-Sachs.
For further information

ICORD 2014 Annual Meeting: Societal value of Prevention, Diagnosis and Treatment of Rare Diseases
Date: 7-9 October, 2014
Venue: Ede, The Netherlands

The ICORD annual meeting will be held jointly with the FIGON Dutch Medicine Days. The conference will propose interactive sessions with ZonMw, the Dutch Drug Evaluation Board, the Dutch Clinical Trial Foundation, ICORD working groups and IRDiRC.
Sessions will include: prevention, diagnosis and neonatal screening; orphan drugs and personalised medicine; patient views; registries and biobanks; and international collaborations.
Healthcare professionals, research, academia, industry, regulatory authorities, policy makers, patient representatives and media are invited to participate.
For further information

The Translational Science of Rare Diseases: From Rare to Care II
Date: 8-10 October, 2014
Venue: Herrenchiemsee, Germany

This meeting will bring together high-profile scientists from around the world, active in the field of rare disease research and translational medicine, and will focus on how basic science on rare diseases can have an impact for the development of novel therapeutic strategies.
For further information

International Symposium on liver-directed gene therapy for rare diseases
Date: 9 October, 2014
Venue: Pamplona, Spain

The Symposium will bring together leading experts in basic and clinical fields of rare diseases and gene therapy, providing an opportunity for clinical experts, research scientists and patients to meet to discuss issues that remain unclear or controversial concerning these complex diseases. The symposium will feature the latest advances in the study of rare diseases such as Porphyria, Hyperoxaluria, Wilson disease, Sanfilippo A and B and Crigler- Najjar diseases, covering aspects from basic research to translational and clinical investigation, with particular interest in novel gene therapies.
For further information

9th ISNS European Neonatal Screening Regional Meeting
Date: 12-15 October, 2014
Venue: Birmingham, UK

This conference will focus on neonatal screening for various diseases.
For further information

Dysmorphology and Radiology of Inborn Errors of Metabolism
Date: 16-17 October, 2014
Venue: Manchester, UK

The topics covered will be of interest to clinicians who deal with rare disorders or have an interest in clinical genetics, IEMs or paediatrics. Participants are expected to have some background knowledge of the field, although extensive experience is not required. Participants are strongly recommended to bring interesting, unusual or unsolved cases for discussion.
For further information

II International Conference on Rare Cardiovascular Diseases
Date: 16-17 October, 2014
Venue: Krakow, Poland

Under the Development of the European Network in Orphan Cardiovascular Diseases framework, co-funded by the Malopolska Regional Operational Programme, the conference is aimed at general physicians and experts treating patients with rare cardiovascular diseases. Discussions will also cover the healthcare system organisation for this group of patients. The conference is aimed at strengthening awareness on the need to coordinate research, disease registries and knowledge exchange to improve care for patients with rare cardiovascular diseases.
For further information

International Scientific Symposium on Angelman Syndrome 2014
Date: 17-19 October, 2014
Venue: Paris, France

Organised by the French Angelman Syndrome Association (AFSA), the symposium will bring together international scientists studying the mechanisms associated with Angelman syndrome and promote exchanges between researchers to advance research in genetics and neuroscience on this rare disease. The meeting is open to official representatives of European and national Angelman syndrome organisations (up to 2 persons per organisation).
For further information

64th Annual Meeting of the American Society of Human Genetics: ASHG 2014
Date: 18-22 October, 2014
Venue: San Diego, US

The ASHG Annual Meeting is the largest human genetics meeting and exposition in the world. This year’s meeting is expected to attract over 6,500 scientific attendees and over 200 exhibiting companies. ASHG members and leading scientists from around the world are selected to present their research findings at invited, platform, and poster sessions. Abstracts of work submitted for presentation at the Annual Meeting are published online and are citable. ASHG's Annual Meeting also features a trade show floor that offers attendees the opportunity to view state-of-the-art medical and laboratory equipment, products, services, and computer software designed to enhance human genetics research, teaching, and consultation.
For further information

NORD’s Rare Diseases and Orphan Products Breakthrough Summit
Date: 22-23 October, 2014
Venue: Alexandria, Virginia, US

The 2014 Breakthrough Summit will concentrate on innovative content and will welcome the top leaders from the FDA, NIH, Industry, Patient Groups, Payers and Research Institutions to address the progress of rare disease diagnosis, genomics, drug development, patient engagement, product approvals, FDA oversight and market accessibility to orphan products.
For further information

14th International Congress on Neuronal Ceroid Lipofuscinoses (Batten Disease)
Date: 22-25 October, 2014
Venue: Córdoba, Argentina

Batten disease is a common name for a group of rare, neurodegenerative genetic disorder affecting approximately 1 in 30,000 individuals. This conference will bring together experts on the latest research into Batten disease, experimental therapies, and clinical perspectives. Workshops will also be organised, covering topics such as patient registries and ethical issues.
For further information

International VHL Medical Symposium
Date: 23-25 October, 2014
Venue: Madrid, Spain

Biennial International VHL Medical Symposia bring together the leaders in VHL basic, translational and clinical research, as well as the leading clinicians in clinical treatment for VHL. The gathering creates a stimulating environment while helping to make connections among these professionals that will spur the pace of progress in understanding and treating VHL. The content is aimed at medical researchers and healthcare professionals. Patients and caregivers are encouraged to attend. Their participation is highly valued as they are the true authorities of von Hippel-Lindau.
For further information

30th Annual Meeting of the Histiocyte Society
Date: 28-30 October, 2014
Venue: Toronto, Canada

The Annual Meeting of the Histiocyte Society serves as the main forum for many of the world's most accomplished histiocytosis researchers and medical professionals to engage in vital collaboration and dialogue with one another. This year, the Society's 30th Annual Meeting will feature presentations on the study and treatment of the histiocytic disorders. Society members will present updates on ongoing Society-sponsored clinical trials on the histiocytic disorders.
For further information

ESID Meeting 2014
Date: 29 October - 1 November, 2014
Venue: Prague, Czech Republic

The 16th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2014), offers access to the latest research and analysis in the field. Meeting participants will gain insights into innovative perspectives in both basic and clinical research. The scientific programme will draw together experts from around the world to discuss breakthroughs in diagnostic immunology, genetics and immunobiology of human diseases, advances in clinical practice, novel therapeutic approaches to tolerance induction and new insights into stem-cell and cellular therapies.
For further information

New frontiers in Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation: From Benchside to Bedside
Date: 30 October - 1 November, 2014
Venue: Stresa, Italy

This third joint symposium on Neuroacanthocytosis addresses neurologists, interns, haematologists and biotechnologists working in the field of diagnostic, clinical and therapeutic management of patients affected by Neuroacanthocytosis and brain iron accumulation diseases. The scientific issues of this meeting will cover both the identification and characterisation of new aspects of this condition, as well as clinical developments.
The international NBIA umbrella patient organisation NBIA Alliance offers travel grants for postdoctoral fellows and early career clinical doctors, involved in NBIA research and interested to attend the 3rd Joint NA & NBIA Symposium.
For further information

2nd International Rare Diseases Research Consortium (IRDiRC) Conference
Date: 7-9 November, 2014
Venue: Shenzhen, China

The second conference is organised by the International Rare Diseases Research Consortium (IRDiRC), in collaboration with the BGI. The conference will gather top scientists from Europe, North America and Asia-Pacific for dynamic exchanges on knowledge and expertise. The event will also include an educational track. The ambition of this conference is to provide researchers with opportunities to establish new collaborations and confront different cultural approaches to the challenges posed by rare diseases.
For further information

4th Pan-European Conference on Haemoglobulinopathies and Rare Anaemias
Date: 7-9 November, 2014
Venue: Athens, Greece

The 4th Pan-European Conference on Haemoglobinopathies and Rare Anaemias aims to educate and empower patients, develop European expert collaborative networks and improve multidisciplinary interaction concerning policy decision making.
For further information

Third International Symposium on Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)
Date: 12-13 November, 2014
Venue: Montreal, Canada

The Montreal Neurological Institute and Hospital will host the 3rd International Symposium focusing on advances in understanding ARSACS (Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay) in the larger context of mitochondrial dysfunction in neurodegeneration. This two day symposium will bring together clinical, ataxia, and mitochondrial experts, as well as drug developers, to discuss how to accelerate the discovery of treatments for ARSACS.
For further information

Ataxia Telangiectasia Clinical Research Conference 2014
Date: 13-15 November, 2014
Venue: Nijmegen, The Netherlands

The bi-annual A-T Clinical Research Conference 2014 brings together leading figures from the fields of clinical science and translational research in Ataxia-Telangiectasia. The objective of the conference is to share knowledge and map progress in the fields of current research and help identify priorities for future research and opportunities for collaboration. The programme includes lectures, presentation of selected abstracts, a poster session, four workshops, a ‘best poster prize’ and a social programme.
For further information

Cilia 2014
Date: 18-21 November, 2014
Venue: Paris, France

Cilia 2014 will focus on (but not be limited to) recent advances in cilia structure and function, including trafficking, cilia and development, cilia in human genetic disease and cilia in infectious microorganisms. The event is organised by four European cilia networks: GDR CIL (France), the Ciliopathy Alliance, the Nordic Cilia & Centrosome Network (Scandinavia) and the EU-FP7 SYSCILIA programme.
For further information

European Williams Syndrome Conference
Date: 21-23 November, 2014
Venue: Budapest, Hungary

The European Federation of Williams Syndrome (FEWS) organises, with the Hungarian Williams Syndrome Association (HWSA), this conference to raise awareness, increase interaction between stakeholders and establish international cooperation.
The focus is to share good practice and knowledge on the disease between European Countries with a good expertise and other European Countries with lesser experience on the syndrome. The ultimate goal is to improve patient care and contribute to EU policy on rare diseases.
The conference targets healthcare professionals, caregivers, politicians, patient organisations, researchers and academics, national authorities, medical societies, health industry, media, etc., as well as professionals from countries with limited knowledge about the syndrome, in order to spread awareness.
For further information

22nd René Touraine Foundation for Dermatology Scientific Meeting
Date: 5 December, 2014
Venue: Paris, France

Every year, the Scientific Meetings go over any acquired knowledge on one skin cell. Mornings are reserved for fundamental approaches, while afternoons are devoted to approaches applied to physiopathology, pharmacology and therapeutic. These are multi-subject meetings. Each presentation starts with a general overview of the terminology used, and continues with the speaker’s own research.
For further information

6th International Meeting on Pulmonary Rare Diseases and Orphan Drugs
Date: 27-28 February, 2015
Venue: Milan, Italy

The International Meeting on Pulmonary Rare Diseases and Orphan Drugs is the only European event dedicated to different types of rare pulmonary diseases affecting both parenchymal and vascular structures. The meeting will be an opportunity to exchange and disseminate knowledge among experts in different areas of clinical and basic research in respiratory medicine, in efforts to provide new insights into science and clinical care, thus helping patients and supporting doctors.
For further information

Trisomy 21 Research Society (T21RS) International Conference
Date: 4-6 June, 2015
Venue: Paris, France

T21RS promotes research on Down syndrome and stimulates collaboration between researchers worldwide. The first edition of the T21RS International Conference will be held at the site of the Hôpital de la Pitié-Salpêtrière in Paris. More details will be announced in due course.
For further information

7th International Conference on Children’s Bone Health
Date: 27-30 June, 2015
Venue: Salzburg, Austria

The International Conference on Children’s Bone Health (ICCBH) meetings provide an international forum for the presentation and discussion of current basic and clinical science in the field of bone metabolism and bone mass in children, adolescents and young adults.
The call for abstracts opens in September 2014.
Abstract deadline: 6 February 2015.
For further information

2nd International Primary Immunodeficiencies Congress (IPIC)
Date: 5-6 November, 2015
Venue: Budapest, Hungary

The International Patient Organisation for Primary Immunodeficiencies (IPOPI) announces the Second International Primary Immunodeficiencies Congress (IPIC). This event will build on the successful outcomes of the first IPIC, attended by 400 participants. The congress will consist of a two-day programme and is open to all stakeholders with an interest in clinical management of primary immunodeficiencies (PIDs).
For further information

13th International Congress of Human Genetics (ICHG) 2016
Date: 3-7 April, 2016
Venue: Kyoto, Japan

Hosted by the East-Asian Union of Human Genetic Societies (EAUHGS) and the Japan Society of Human Genetics, the 13th ICHG will focus on progress in genome analysis technologies and big data in order to explore disease mechanisms and treatment opportunities.
Registrations open in 2015.
For further information


Commercial events

Orphan Drugs and Rare Diseases
Date: 20-21 October, 2014
Venue: London, UK

SMi present the 3rd Annual Orphan Drugs and Rare Diseases Conference. The Orphan Drugs market is set to rise as a result of pharmaceutical companies now looking to orphan drugs as an essential revenue stream with 2014 set to be the year to see Orphan adoption.
For further information

3rd annual World Biosimilar Congress
Date: 11-12 November, 2014
Venue: Geneva, Switzerland

The 3rd annual World Biosimilar Congress offers keynotes, case studies and roundtables covering topics relating to process, production, regulation and marketing strategies for biosimilars. Speakers and attendees include industry executives, middle managers, academics, key influencers and end-users.
For further information

The World Orphan Drug Congress Europe 2014
Date: 12-14 November, 2014
Venue: Brussels, Belgium

The World Orphan Drug Congress Europe offers partnering opportunities in the orphan and rare disease field. Key networking platforms include: Dedicated networking functions; Privately hosted meeting areas; Online partnering portal and access to free smartphone app; Personal networking managers to assist in meeting scheduling.
For further information


Media, Press & Publications

Article series on innovative approaches to study and treat rare diseases

As the number of discovered rare diseases continues to increase, the search for innovative methods to understand rare disease complexity and bring about novel therapies has also accelerated over the past decade. In an editorial published in the Journal of General Internal Medicine in August, Kesselheim and Gagne introduce a series of fourteen articles on innovative approaches to study rare diseases, optimise data sources, involve patients in research and develop health policy.

In their article, Retsch-Bogart et al. propose measures to identify strong clinical research teams to lead research on rare diseases.

Five further articles explore methods of collecting and optimising use of data on rare diseases.
Nigwekar et al. and Royer et al. propose novel processes to analyse data on rare disorders and identify patients. Krischer et al. describe the Rare Disease Clinical Network. Presented in
OrphaNews of 18 September, the article describes the network of consortia to collect data, connect with patients and support clinical studies. Thompson et al. describe the experience of RD-Connect, a platform to integrate data from registries, genomics, biobanks and bioinformatics, also reported in
OrphaNews of 18 September. Maro et al. describe novel approaches to post market pharmacovigilance for orphan drugs.

Three articles describe the role of patients in rare disease research and orphan drug development.
Thyen et al. evaluate patient care satisfaction in certain rare disease groups. Poon et al. study the long term impact of chronic rare disease on quality of life. Forsythe et al. explore methods of engaging patients in research, described in today’s OrphaNews.

Finally, four articles explore regulatory, economic, social and ethical issues concerning the benefits of rare disease treatment and health outcomes. Abrahamyan et al. describe value-of-information methods to assess the cost-benefits of expensive treatments for rare diseases. Winquist et al. describe the Canadian experience of developing a framework for orphan drug reimbursement decisions, previously reported in OrphaNews of 18 September. Pariser and Gahl present general advances in translational approaches to advance drug discovery for rare diseases. Finally, Basch and Bennett describe the relevance of incorporating patient-reported outcomes into clinical trials on rare diseases, also reported in
OrphaNews of 18 September.

Read the open access introduction to a supplement
Access the PubMed abstracts for open access to the articles

Future Medicinal Chemistry: special issue on rare diseases

A series of articles in this special issue explore the application of medicinal chemistry and innovative approaches to advance the discovery and development of orphan therapies for rare diseases.

Read the open access foreword to the Special Focus Issue: Rare Diseases
Consult the list of articles

Advances in Predictive, Preventive and Personalised Medicine

This book focuses on advances in predictive, preventive and personalised medicine (PPPM) to treat rare diseases. Chapters describe therapeutic development in the context of national plans for rare diseases, registries and biobanks, diagnostics and novel therapies among other topics.

Editor: Meral Özgüç
Advances in Predictive, Preventive and Personalised Medicine: Rare Diseases
Integrative PPPM Approach as the Medicine of the Future
Volume 6, 2015, XVIII, 208 p.
eBook: ISBN 978-94-017-9214-1 (€ 118.99)
Hardcover: ISBN 978-94-017-9213-4 (€ 147.69)

Consult the book description

Paediatric pharmaceutical legislation in the USA and EU and impact on adult and paediatric drug development

In this chapter, Rose compares and contrasts paediatric legislations in the US and the EU and their impact on paediatric drug development.

Editor: Klaus Rose
Pediatric Formulations
AAPS Advances in the Pharmaceutical Sciences Series
Volume 11, January 2014, pp 405-419

Consult the abstract


OrphaNews, The Newsletter of the Rare Diseases Community.
OrphaNews is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Antonia Mills
Editors for Scientific Content: Catherine Pouzat, Sophie Höhn
Contact Us
Editorial Board: Ségolène Aymé, Paul Boom, Anna Bucsics, Kate Bushby, Barbara Cagniard, Lorenzo Dagna, Adam Heathfield, Lilian Lau, Yann Le Cam, Jordi Llinares-Garcia, Antoni Monserrat, Charlotte Rodwell, Gerhard Steffes, Till Voigtländer, Jaroslaw Waligora

Orphanet Partner Country Representatives: Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Joerg Schmidtke (Germany), Helen Michelakakis (Greece), Eileen Treacy (Ireland), Annick Raas-Rothschild (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Vaidutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
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Photo credit : Serimedis http://www.serimedis.inserm.fr/ (unless otherwise stated)