27 January 2016 print
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Application of a national concept and framework conditions for creation and implementation of Reference Centres for Rare Diseases in Switzerland

Recommendations of a working group of the Academie Suisse des Sciences Medical (ASSM) for the Federal Health Office Public in Switzerland have been published.

The Federal Council of Switzerland instructed the (Office fédéral de la santé publique) OFSP to develop a "National Strategy for Rare Diseases" in collaboration with various stakeholders. In this context the President and the Secretary General of the ASSM met with a delegation of CI Rare diseases and concluded that it would be desirable that a working group of the ASSM made recommendations describing the scope of a "National Strategy for rare diseases." At the same time, the working group would sketch the framework conditions as prerequisites diagnostic and therapeutic interventions in Reference Centres for the prerequisite rare diseases. This working group aimed to dispel concerns of the risk of an uncontrolled increase in the cost for these measures, which in turn could contribute to a better acceptance of the "National Strategy for Rare Diseases."

In this framework, conditions for the creation and implementation of Reference Centres for rare diseases was delineated. According to ASSM, the following cases fall within the competence of Reference Centres for rare diseases:

a. the disease in question requires a high level of knowledge and specific experience;
b. because of the low prevalence, the cases should be consolidated to ensure adequate support ;
c. prevention, diagnosis and treatment requiring specific techniques, technologies and sophisticated procedures.

According to the ASSM the mission of the Reference Centres should include:
Care benefits: Reference Centres should meet specific medical needs which should include rehabilitation and palliative care of patients with rare diseases. For this, they should coordinate, within their specific areas of care, skills and qualifications of several disciplines, including non-medical and social skills.
Networking: Reference Centers should cooperate with other Centres of Reference - national and international - as well as specialized centres and patient organisations. They should also network with specialised laboratories and other institutions.
Guidelines: Reference Centers should observe the guidelines for good practice along with participating in their development, dissemination and updating.
Research: Reference Centres should engage in research, improvement of disease understanding and optimisation of diagnosis, treatment and management.
National Register: Reference Centres should list all patients with rare diseases in a national registry.

The ASSM has also summarised the rights of Reference Centres, which include the right to treat all patients referred to them, the right to be included as partners in the process for supporting costs, the right and duty to treat patients across borders. For a Reference Centre to be recognised, they must complete most of the criteria outlined by the ASSM which includes the minimum set of criteria that should be followed. Further information can be found on the Swiss Orphanet website

Spotlight on...
Validation of the Second National Disability Scheme in France
In France, the national scheme of social and medico-social organisation for rare handicaps for 2014-2018 has been published. The publication of this scheme by ministerial decree opens after a delay of two months to introduce an administrative appeal to the Minister on a contentious appeal with the Council of State. After the first scheme 2009-2013 which set up the territorial organisation of the plan and funding of seven interregional projects and four resource centres, the pattern 2014-2018 aims to consolidates and improve the previous scheme through four main objectives:

• The continued deployment of the integrated organisation within the territories through the establishment of relay teams and development of information;
• Improving the quality, continuity of life course and access to resources for all ages; increased support for caregivers within the family, the development of specific receptions in facilities and services for rare disabilities and ensuring better support of aging people with disabilities;
• Improving knowledge, promoting research and the culture of sharing in case of Rare handicaps.
For further information (in French)


National & International Policy Developments
Other European news
Symposium on the development of European cooperation on health technology assessment
In France the Haute Autorité de Santé (HAS) organised a symposium on October 30th, 2015, addressing European cooperation in evaluation of health technologies - an approach initiated more than a decade ago with the creation of European Network for Health Technology Assessment (EUnetHTA) network. EUnetHTA was launched in 2006 to create an operational and sustainable European network. It organises the collaboration between the agencies responsible for evaluation of health technologies in Europe and facilitates the exchange of knowledge and best practices. Five European programs were highlighted during this program which are mentioned below

Early dialogue between the HTA institutions and industry, about the nature of the data to be collected during the clinical trials of a new treatment is important. The goal of this programme is to improve the quality of data obtained during development of drugs and other health products. SEED is a consortium of 14 national and regional rating agencies in Europe driven by the HAS. So far HAS has coordinated 24 meetings with industrialists, for medicines, medical devices, implantable devices and diagnostic tests.

AdHopHTA integrates information for several European hospitals to help them choose the confirmed innovations, and to eliminate expensive technology and without real benefit.

MedtecHTA aims to conduct comprehensive assessments of medical devices taking into account the complexity of their integration into clinical practice.

Advance HTA
The HTA Advance project brings together 12 partners to focus on specific methodological issues, particularly the specific treatment of rare diseases and practices on medical devices.

Integrate-HTA brings together seven partners from five different countries to study palliative care. The work involves conducting comprehensive patient focussed evaluations on economic and sociocultural factors affecting them.
For further information (in French)

Telegenetics in Europe: current usage and constraints
An article published in European Journal of Human Genetics address an interesting issue of including telemedicine to overcome physical and economic barriers to providing genetic services. The authors assessed the use of telegenetic usage among genetic professionals in Europe and found that its usage was limited. Telephone genetic counselling was used by 17% of the respondents, while videoconferencing was used to a lesser extent. The respondents cited many constraints that dissuaded them from using telegenetic modalities.

The authors advocate “professional cooperation, sharing knowledge, and establishing guidelines on a national and international level” to combat these constraints. Additionally, the authors recommend involving “both professionals and patients in establishing and expanding telegenetics initiatives and in establishing practical guidelines” as it is done in the United States by the American Telemedicine Association for various disciplines. They believe establishing a European Working Group on telegenetics addressing the constraints mentioned in the article would help with its wider application.
Read the Pubmed Abstract

Policy recommendations for reference centres for rare/complex cancers in Belgium
Due to the view of many that it is no longer practicable, efficient or ethical that every hospital or every practitioner continues to offer care for every rare/ complex cancer, the Ministry of Health of Belgium has ordered an enquiry into the organisation of hospitals for this kind of care. An article published in Epidemiology and Public Health presents recommendations, after conducting an extensive literature survey and interviews, for the organisation of care for adults with rare and/or complex cancers in Belgium.

The authors recommend setting up of expert reference centres that will offer the patients with diagnostic confirmation, treatment plan, which will be followed up by peripheral centres for less complex tasks. The authors believe that the expert centres have to meet strict criteria to ensure a truly multidisciplinary approach with the availability of skilled nursing and paramedical staff and ensure proper certification. They also advocate increasing the concentration of patients in these centres by imposing a minimum caseload. Of great importance, according to the authorss, is the appointment of a patient-liason coordinator for transmission of information to the patients. Finally, they advocate active involvement in clinical research and creating national and international collaboration.

The authors also provide three approaches – legal, financial, pragmatic - by which these policy recommendations can be transformed to policy decisions.
Read the Pubmed abstract

Other International News
Accessing orphan drugs in Turkey
Even though Turkey does not have an orphan drug legislation, there are some regulatory mechanisms through which patients of rare diseases can avail orphan drugs. An article published in PharmExec notes that patients of Turkey has access with reimbursement to 62 of the 85 orphan drugs approved in the European Union in 2015. According to the authors this number is higher than in some EU member states. This is significant, as according to the authors, “Turkey is home to an estimated five million rare disease patients” due to consanguinity featuring higher than Europe in the Turkish society, especially in the Eastern part.

There are three channels available to obtain unapproved products, according to the Ministry’s latest (2014) Guidelines on the Importation of Medicines and Their Use. These channels include off-label use of drugs approved in Turkey, Personal importation under the responsibility of the patient’s physician for products approved in another major jurisdiction (US, EU) or through their compassionate use Program for patients with life-threatening or other serious diseases –this can include products which have completed Phase 2 and started Phase 3 trials overseas.
Read the article

Rare Diseases International launches new website
Rare Diseases International (RDI) is the global alliance of people living with a rare disease of all nationalities across all rare diseases. Currently, embedded in Eurordis, it brings together national and regional rare disease patient organisations from around the world as well as international rare disease-specific federations to create the global alliance of rare disease patients and families. RDI has launch a new website with a goal provide current and prospective members, as well as all stakeholders, with information on RDI, what it will do and how to get involved.

RDI asks members to send their news and upcoming events in order to promote them on the Member News & Events section. The site also contains integrated social media buttons and the RDI Discussion Group that is embedded in the RareConnect online patient communities platform, familiar to many around the world. You can use the RDI Discussion Group to ask a question, share an experience or disseminate your news to a target audience. RDI is currently looking for volunteer translators and mother tongue proofreaders in order to make the rest of the website available in other languages too.

The involvement of patient organisations in rare disease research in Australia
An article published in the Orphanet Journal of Rare Disease reports that active role Australian rare disease patient organisations (RDPOs) are playing in advancing rare disease research. According to this study a majority of the surveyed RDPOs actively promote research on the diseases affecting their members and are involved in research-related activities in the previous five years. The authors also report the considerable challenges in meeting their research goals, mainly due to insufficient resources, and a perceived lack of interested researchers. The authors base this on the lack of specific policies and resources in Australia as well as the dearth of partnerships among RDPOs.
Access the article

Guidance Documents and Recommendations
Recommendations for health care professionals on partnering with parents to disclose Klinefelter syndrome to their child
An article published in Acta Paediatrica provides information and recommendations to health care professionals on how they can help parents disclose the diagnosis of Klinefelter syndrome to their child(ren). The authors point out that a diagnosis of Klinefelter syndrome – a chromosomal abnormality causing physical and intellectual disabilities – can be made after prenatal testing or due to symptoms that present later in life. The authors realise the complexity of disclosing of this diagnosis to young patients and recommend recommendations for health care professionals regarding disclosure of a diagnosis of Klinefelter syndrome to a Child. They provide several strategies, emphasising “gradual and personalized disclosure process” for patients with a prenatal diagnosis as well as encouraging a personalised disclosure for patients that are diagnosed later in life.
Read the Pubmed abstract

Bioinformatics, Registries and Data Management
Registry data shows unfavourable consequences of Fanconi Anaemia in Italy
An article published in Haematologica describes the twenty year experience of the Italian Fanconi Anemia Registry. The registry collects clinical, epidemiological and genetic data of Italian Fanconi Anemia patients, which currently includes 180 patients with a confirmed diagnosis. The report focusses on the natural history of the disease which remains hard to establish because of its rarity and its "heterogenous clinical presentation, frequent therapeutic modalities and long-term outcome of the patients in the registry."

According to the authors majority of patients reported haematological abnormalities at the initial presentation, and many underwent a bone-marrow transplant, with increasing incidence of cancer and decreasing survival over the course of time. According to the authors, the data collected by their registry over the period of time reveals no major improvement in treatment or survival of patients with Fanconi anemia over the years.
Read the PubMed abstract

ProteinPaint – a novel web application for visualising paediatric cancer genomic data
The utility of ProtienPaint – “for simultaneously visualising genetic lesions and RNA expression in paediatric cancers” is described in Nature Genetics. According to the authors this is the first portal that focusses on paediatric cancer, providing information on possible “pathogenic germline mutations, gene fusions and mutation stratification by cancer subtype.” The portal contains a wide variety of data from various subtypes of paediatric cancer, which was compiled from five major studies. According to the article users can visualise genetic lesions from pediatric cancers simultaneously with mutations in adult cancers (for eg., from the COSMIC database) thus enabling the possibility of comparing and contrasting and in turn interpreting the significance of rare genetic lesions in pediatric cancer and adult cancers. The authors present ProteinPaint as a gene portal that complements the existing ones by “providing a comprehensive and intuitive view of pediatric cancer genomic data with advanced visualization features, as well as integration of expression and adult cancer data.”
Access the article

Screening and Testing
Statement on the utilisation of whole-genome sequencing in newborn screening
The progress in whole genome sequencing technology has been gaining ground leading to a significant decrease in both the cost and time needed to generate data on the entire sequence of the human genome and an increase in accessibility especially for newborn screening programs (NBS). An article published in European Journal of Human Genetics describes the impact this will have on the potential use of this technology in publicly funded newborn screening programmes. The article presents a statement from The Public and Professional Policy Committee of the European Society of Human Genetics, the Human Genome Organisation Committee on Ethics, Law and Society, the PHG Foundation and the P3G International Paediatric Platform reviewing the current scenario and issues “a set of recommendations to help inform and guide scientists and clinicians, as well as policy makers”. These recommendations include

• The primary objective of genome sequencing in NBS should be prevention and or treatment
• There should be robust evidence base to conduct these screenings
• Cost-effectiveness studies to ensure proper implementation and monitoring are imperative
• Open dialogue between stakeholders holds the key to advance engagement
• Necessary information should be provided to parents at all stages
• Particular attention should be paid to educating health care professionals on this topic
• A properly thought out plan for the future of the stored data should is required
• Unsolicited findings which lead to a preventable or treatable health problem should be communicated
Read the PubMed abstract


Ethical, Legal & Social Issues
Petition by neuromuscular specialists in the United States on Firdapse pricing
Jacobus Pharmaceutical, a small family owned company, supplied 3,4 diaminopyride (3,4 DAP) to patients afflicted with Lambert-Eaton myasthenic syndrome (LEMS) a for free in the United States and $100 a month in Canada, through a compassionate care program. However, Catalyst Pharmaceutical is on the heels of obtaining marketing authorisation from the United States Food and Drug Administration on the unrefrigerated version of this drug called Firdapse. Concerned physicians across the US have signed a petition which is published in Muscle and Nerve, citing that if the company gets exclusive rights to sell the drug for seven years, there could be “potentially harmful price increase” and have asked for “ethical and just pricing.” The petitioners also ask for “a revision of the ODA to close the loophole that permits pharmaceutical companies to exploit market exclusivity of existing, inexpensive compounds for which they did not provide significant developmental investment.”
Read the article in New York Times

Study claims alleviation of economic burden of Cushing’s disease by therapeutic intervention
Cushing’s disease is a rare endocrine disorder caused by a cortisol-secreting pituitary tumor and associated multiple chronic comorbidities which affect patients over their lifetime, causing tremendous patient and cost burdens.

A study published in Expert Opinion on Orphan Drugs attempts to estimate the cost-effectiveness of the treatment approaches for the various clinical comorbitities by analysing published literature on “prevalence of comorbidities, cost and clinical effectiveness of treatments for controlled and uncontrolled disease from published literature.”. From the data collected the authors report that the “total (estimated) annual cost of comorbidities among patients with uncontrolled or controlled disease to be $29,386 and $13,236. The lifetime cost burden from comorbidities was estimated to be $881,573 for a patient with uncontrolled disease, with lifetime cost savings of $484,483.”
Access the article

The importance of genetic diagnosis for Duchenne Muscular Dystrophy
An article published in Journal of Medical Genetics describes the “different mutations causing DMD, diagnostic techniques available for making a genetic diagnosis for children suspected of DMD and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies for DMD.” According to the authors a confirmed genetic diagnosis is paramount for any rare disease, including DMD as it “has implications for disease prognosis, genetic counselling and evaluating each patient’s eligibility for emerging genetic therapies” in order to provide them with mutation specific therapies Diagnosis for DMD can be made sooner than before, and the authors believe that “raising awareness with family physicians and other healthcare professionals who see young children could improve this further” and could even be possible to screen the disease in newborns, which would greatly help in the success of genetic therapies for this disease.
Access the article

Pre- and post-test genetic counseling for chromosomal and Mendelian disorders
A review published in Seminars in Perinatology explores three areas of technical expansion in genetic testing: expanded carrier screening, non-invasive prenatal screening for foetal aneuploidies using cell-free DNA, and diagnostic testing using foetal chromosomal microarray testing, and provides insights aimed at enabling the obstetrical practitioner to better support patients considering these tests. According to the authors the complexity of genetic testing options available to patients in preconception and prenatal care is expected to continue to grow, and likely at a rapid pace with the advent of new molecular and bioinformatics technologies. Due to this the author believe that to provide optimal patient care, it is essential that obstetrical care providers stay up-to-date regarding available technologies as well as the overall benefits, drawbacks and limitations of various testing options.
Read the Pubmed abstract

Interest in diseases of low prevalence over the centuries
In a letter to the editor of Orphanet Journal of Rare Diseases the author addresses a historical persepective of interest in “disorders with a low prevalence”. The author believes that there has always been (an) interest on part of the medical and pharmaceutical profession in the diagnosis and treatment of disorders with low prevalence”. The author presents the Rembert Doedens book “Medicinalium observationum exempla rara, recognita et aucta” written more than 500 years ago, which lists more than 200 diseases of low prevalence during the period. The author also details the role of compounding pharmacists over the centuries for providing “off-label” medications for certain rare diseases.
Access the article


New Syndromes

Childhood-juvenile onset Emery-Dreifuss-like phenotype without cardiomyopathy caused by a novel homozygous mutation of the TTN gene
Three patients from three different families shared similar features of a new titinopathy: coexistence of limb-girdle weakness and early-onset diffuse joint contractures without cardiomyopathy. The biopsies showed rimmed vacuoles, a dystrophic pattern, and secondary reduction in calpain 3. The authors identified a novel homozygous mutation in the TTN gene in the three patients.
Consult the Pubmed abstract

Neurology ; 85(24):2126-35 ; December 2015
Thrombocytopenia with excessive bleeding and platelets due to SLFN14 mutations
The authors evaluated 36 unrelated patients and 17 family members displaying thrombocytopenia. All patients had a history of excessive bleeding of unknown etiology. They performed platelet phenotyping and whole-exome sequencing (WES) on all patients and identified mutations in SLFN14 in 12 patients from 3 unrelated families. Patients harboring SLFN14 mutations displayed an analogous phenotype that consisted of moderate thrombocytopenia, enlarged platelets, decreased ATP secretion, and a dominant inheritance pattern.
Consult the Pubmed abstract

J Clin Invest. ; 125(9):3600-5 ; September 2015
A novel muscular dystrophy, severe cardiomyopathy and triangular tongues associated with LIMS2 mutations
The authors presented two adult siblings with childhood-onset of weakness progressing to a severe quadriparesis with the additional features of triangular tongues and biventricular cardiac dysfunction. Whole exome sequencing identified compound heterozygous missense mutations in LIMS2.
Consult the Pubmed abstract

Clin Genet. ; 88(6):558-64 ; December 2015

New Genes

Heritable pulmonary arterial hypertension caused by a homozygous mutation of EIF2AK4 in five Iberian Gypsies families
Consult the Pubmed abstract
To read more about "Heritable pulmonary arterial hypertension"

Clin Genet. ; 88(6):579-83 ; December 2015
Renocular ciliopathies due to mutations in IFT81
Consult the Pubmed abstract
J Med Genet. ; 52(10):657-65 ; October 2015
Chronic non-specific multiple ulcers of the small intestine associated with loss-of-function mutations in SLCO2A1
Consult the Pubmed abstract
PLoS Genet. ; 11(11):e1005581 ; November 2015
Coenzime Q10 deficiency linked to mutations in COQ4 and COQ7
Consult the Pubmed abstracts
To read more about "Coenzyme Q10 deficiency"

J Med Genet. ; 52(9):627-35 ; September 2015
J Med Genet. ; 52(11):779-83 ; November 2015
Venous malformation caused by somatic activating PIK3CA mutations
Consult the Pubmed abstract
To read more about "Mucocutaneous venous malformations"

Am J Hum Genet. ; 97(6):914-21 ; December 2015
Woolly hair associated with a homozygous missense variant in KRT25 in two unrelated consanguineous Pakistani families
Consult the Pubmed abstract
To read more about "Woolly hair"

J Med Genet. ; 52(10):676-80 ; October 2015
Linear and sporadic syringocystadenoma papilliferum linked to a somatic BRAF mutation
Consult the Pubmed abstract
To read more about "Syringocystadenoma papilliferum"

J Invest Dermatol. ; 135(10):2536-8 ; October 2015
Neurodegeneration with brain iron accumulation: SCP2 as a candidate gene
Consult the Pubmed abstract
To read more about "Neurodegeneration with brain iron accumulation"

Neurology ; 85(21):1909-11 ; November 2015

Research in Action

Clinical Research
Duchenne muscular dystrophy: the use of deflazacort is associated with later loss of independent ambulation but increased frequency of side effects
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Neurology ; 85(12):1048-55 ; September 2015
Postsynaptic congenital myasthenic syndromes: salbutamol and ephedrine are effective and well tolerated treatments
Consult the Pubmed abstract
To read more about "Postsynaptic congenital myasthenic syndromes"

Neurology ; 85(12):1043-7 ; September 2015
Early inhaled budesonide prevents bronchopulmonary dysplasia in extremely preterm infants
Consult the Pubmed abstract
To read more about "Bronchopulmonary dysplasia"

N Engl J Med. ; 373(16):1497-506 ; October 2015
Mantle cell lymphoma: lenalidomide plus rituximab is active as initial therapy
Consult the Pubmed abstract
To read more about "Mantle cell lymphoma"

N Engl J Med. ; 373(19):1835-44 ; November 2015
Paediatric cancer: TP53, APC, BRCA2, NF1, PMS2, RB1 and RUNX1 as the most commonly mutated genes
Consult the Pubmed abstract
N Engl J Med. ; 373(24):2336-46 ; December 2015
Constitutional mismatch repair deficiency syndrome: clinical description of a French cohort
Consult the Pubmed abstract
To read more about "Constitutional mismatch repair deficiency syndrome"

J Med Genet. ; 52(11):770-8 ; November 2015
Therapeutic Approaches

Duchenne muscular dystrophy: simvastatin improves the overall health and function of skeletal muscles in mice
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Proc Natl Acad Sci U S A. ; 112(41):12864-9 ; October 2015
Vestibular schwannoma: anti-VEGF treatment improves neurological function and augments radiation response in a sciatic nerve model
Consult the Pubmed abstract
To read more about "Vestibular schwannoma"

Proc Natl Acad Sci U S A. ; 112(47):14676-81 ; November 2015
Erlotinib prevents sclerodermatous chronic graft versus host disease in a mouse model
Consult the Pubmed abstract
To read more about "Chronic graft versus host disease"

J Invest Dermatol. ; 135(10):2385-93 ; October 2015
Neuroblastoma: FACT inhibition by the small-molecule curaxin compound CBL0137 markedly reduces tumour initiation and progression in a mouse model
Consult the Pubmed abstract
To read more about "Neuroblastoma"

Sci Transl Med. ; 7(312):312ra176 ; November 2015
Two reviews on animal models of craniofacial malformations
Consult the Pubmed abstracts
To read more about "Cleft lip/palate"
To read more about "Treacher-Collins syndrome"
To read more about "Craniosynostosis"
To read more about "Postaxial acrofacial dysostosis"
To read more about "Roberts syndrome"
To read more about "Bardet-Biedl syndrome"
To read more about "Meckel syndrome"
To read more about "Joubert syndrome"
To read more about "Congenital syngnathia"
To read more about "Blackfan-Diamond anemia"
To read more about "Bowen-Conradi syndrome"
To read more about "Orofaciodigital syndrome type 1"

Curr Top Dev Biol. ; 115:459-92; 115:413-58 ; 2015
Down syndrome: new transgenic mouse model
Consult the Pubmed abstract
To read more about "Down syndrome"

Endocrinology ; 156(3):1171-80 ; March 2015
Diagnostic Approaches

Craniofacial disorders: review on clinical and genomic approaches for the diagnosis
Consult the Pubmed abstract
Curr Top Dev Biol. ; 115:543-59 ; 2015
Cutaneous T cell lymphoma: a review and an article on diagnosis
Consult the Pubmed abstracts
Sci Transl Med. ; 7(308):308ra158; 308fs41 ; October 2015

Patient Management and Therapy
Cystic fibrosis: Cochrane review on oral steroids
Consult the Pubmed abstract
To read more about "Cystic fibrosis"

Cochrane Database Syst Rev. ; 12:CD000407 ; December 2015
Charcot-Marie-Tooth disease type 1A: Cochrane review on ascorbic acid for the treatment
Consult the Pubmed abstract
To read more about "Charcot-Marie-Tooth disease type 1A"

Cochrane Database Syst Rev. ; 12:CD011952 ; December 2015
Ebola haemorrhagic fever: review on vaccine research and development
Consult the Pubmed abstract
To read more about "Ebola hemorrhagic fever"

Sci Transl Med. ; 7(317):317ps24 ; December 2015
Craniofacial disorders caused by spliceosomal defects: a review
Consult the Pubmed abstract
To read more about "Mandibulofacial dysostosis-microcephaly syndrome"
To read more about "Nager syndrome"
To read more about "Cerebro-costo-mandibular syndrome"
To read more about "Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome"
To read more about "Richieri Costa-Pereira syndrome"

Clin Genet. ; 88(5):405-15 ; November 2015
Fabry disease: review on gastrointestinal involvement
Consult the Pubmed abstract
To read more about "Fabry disease"

Clin Genet. ; 89(1):5-9. ; January, 2015
Noonan syndrome and related disorders: review on malignant tumours
Consult the Pubmed abstract
To read more about "Noonan syndrome"
To read more about "Noonan syndrome with multiple lentigines"
To read more about "Costello syndrome"
To read more about "Cardiofaciocutaneous syndrome"

Clin Genet. ; 88(6):516-22 ; December 2015
Eosinophilic esophagitis: a review
Consult the Pubmed abstract
To read more about "Eosinophilic esophagitis"

N Engl J Med. ; 373(17):1640-8 ; October 2015
Autoimmune necrotizing myopathy: review on diagnosis and management
Consult the Pubmed abstract
To read more about "Autoimmune necrotizing myopathy"

Curr Rheumatol Rep. ; 17(12):72 ; December 2015
Paediatric acute myeloid leukaemia: review on clinical and biological management aspects
Consult the Pubmed abstract
To read more about "Acute myeloid leukemia"

Biomark Res. ; 3:21 ; October 2015
Primary signet ring cell carcinoma of the colon and rectum: a review
Consult the Pubmed abstract
Bull Cancer ; 102(10):880-8 ; October 2015
Special issue of the ‘Handbook of Clinical Neurology’ on neurocutaneous syndromes
Consult the special issue
Handbook of Clinical Neurology ; 132:2-330 ; 2015
Three new and six 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. Three new GeneReviews have been published for:
CHD2-related neurodevelopmental disorders
7q11.23 duplication syndrome
Progressive pseudorheumatoid dysplasia

Six updated GeneReviews have been published for:
16p11.2 recurrent microdeletion
Creatine deficiency syndromes
Rothmund-Thomson syndrome
Alport syndrome and thin basement membrane nephropathy
Emery-Dreifuss muscular dystrophy
NSDHL-related disorders


Orphan Drugs
FDA approves Uptravi to treat pulmonary arterial hypertension

The U.S. Food and Drug Administration has approved Uptravi (selexipag) to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive, and debilitating rare lung disease that can lead to death or the need for transplantation.

PAH is high blood pressure that occurs in the arteries that connect the heart to the lungs. It causes the right side of the heart to work harder than normal, which can lead to limitations on exercise ability and shortness of breath, among other more serious complications.

Uptravi is an oral IP prostacyclin receptor agonist which acts by relaxing muscles in the walls of blood vessels to dilate (open) blood vessels and decrease the elevated pressure in the vessels supplying blood to the lungs.
Read the FDA press release

Shire purchasing US-based Baxalta
Shire agreed to purchase US-based Baxalta for $32 billion and has, according to industry analysts, consolidated its position as a leading player in the treatment of rare diseases. Baxalta develops biotech treatments for rare blood conditions, cancers and immune system disorders and would provide Shire with a strong portfolio of hemophilia treatments, which accounted for 22% of the total global sales in 2014. According to reports Baxalta will advance Shire's strategy of building out a broad platform within the rare diseases space. For further information
Political and Scientific News
Incorporating Patient Perspectives in Health Technology Assesments and Clinical Practice Guidelines
A study published in Research in Social and Administrative Pharmacy reports on the different ways patients can be involved in health technology assessments (HTA) and clinical practice guidelines (CPG) processes and their challenges, as well as on the approaches that can be used to inform patients about this topic in Finland. While multichannel communication on CPGs and HTAs was seen as essential, the authors also outlined a wide variety of communication channels such as internet/social media, patient organisation, health care professionals and media,. This included incorporating patient representatives in the different stages of HTA and CPG groups. The authors especially note the important role of patient organisations for ensuring the involvement of patients during decision making as well as keeping them informed of the HTA and CPG decisions.
Access the article



CCG Funding Opportunities
The National Cancer Institute (NCI) has published three companion Funding Opportunity Announcements (FOAs) for Genomic Data Analysis Network Centers to support programs of the Center for Cancer Genomics (CCG). The FOAs are managed by CCG and solicit applications for a Processing Genomic Data Center, aVisualization Genomic Data Center, and a Specialized Genomic Data Center.
Access each of the solicitationshere

Medical Research Grant Application Guidelines : Progeria Research Foundation
The foundation is proving several grants such as Innovator Awards, Established Innovator Award, and Specialty Award. Details are provided on their website
AFM Telethon: Call for proposals
Several call for proposals are being made available by AFM Telethon. They have published a call for proposals for Spinal Muscular Atrophy and Collagen VI Call for Projects.
For further information

Call for Applications for Research Grants on Angelman Syndrome: extended deadline
The Angelman Syndrome Alliance (ASA) supports research on Angelman syndrome with up to 300,000 Euros to be awarded at the next International Angelman Syndrome Scientific Conference. Researchers of any country are invited to apply for research grants covering preclinical (basic) research as well as translational research such as mechanism based controlled trials.
Applications for behavioural therapies are not eligible at this point.
Proposals addressing new ideas/concepts about the pathogenesis of Angelman Syndrome are particularly invited. (Deadline 31st of January 2016).
For further information

Congenital Central Hypoventilation Syndrome Family Network
The Congenital Central Hypoventilation Syndrome (CCHS) pilot grant award represents a collaborative effort between the CCHS Family Network and the CCHS Foundation to encourage and support basic, clinical, translational, or epidemiological research to impact the lives of patients with CCHS.

The grant provides up to $30,000 over 1 year for expenses related to the research project, which may include research laboratory supplies, equipment, publication charges for manuscripts that pertain directly to the funded project, and other research expenses. Application Deadline: 29 February, 2016

Kindness for Kids Health Care Award
Kindness for kids will award a maximum of 40,000 euros for the implementation of a project that aims to directly improve the situation of children living with a rare disease through structural changes or with a new therapeutic approach in the area of physiotherapy and psychological care.
For further information

The Jerome Lejeune Foundation
If you are a researcher investigating intellectual disability from genetic origin appearing in early childhood, the Scientific Advisory Board of the Jerome Lejeune Foundation invites you to submit your research project aiming at deciphering the pathophysiology of the cognitive deficits of patients, especially those with trisomy 21 (Down syndrome) and other rare abnormalities such as fragile X, cri du chat, Rett, Williams-Beuren, Prader-Willi, Angelman, and other syndromes, excluding autism. Grants are offered for one or two year(s) within the range of EUR 20 000 per year. Clinical projects could benefit from more funding. Deadline: 7 March, 2016
For further information


Courses & Educational Initiatives

Training Course on Diagnosis and Management of Very Rare Red Cell and Iron Disorders
Date: 29-30 January, 2016
Venue: Lisbon, Portugal

Detailed course on diagnosis and management of these disorders for researchers, doctors and patients.
For further information

European Cytogenetesists Association
Date: February/March of each year
Venue: Nimes, France

This course is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification. The students will be trained to identify genetic abnormalities for diagnosis and prognosis, and for fundamental and applied research using both classical and molecular cytogenetic techniques. The course is co-organized by E.C.A. and two French Universities, either as a stand-alone course with only the theoretical part or as a University Diploma including both theoretical and practical training. An application for CME points will also be made for 2016.
For further information

Course for health care guidelines developers on treatment of rare diseases
Date: 10-12 February, 2016
Venue: Istituto Mario Negri, Milan Italy

The course is part of the capacity building activities of the project RARE-Bestpractices and will provide participants with the opportunity to acquire skills necessary to produce health care guidelines on treatments of rare diseases.
For further information
Visit the Rare Best Practices website

Courses offered by Recordati Rare Diseases Foundation
The Recordati Rare Diseases Foundation is offering five courses planned for next year. For further information, please contact Cecilia Kellquist, Coordinator and member of the board, ckellquist@rrdfoundation.org/www.rrdfoundation.org.

Homocystinurias and defects of folate and methylation metabolism: practical approaches to diagnosis and treatment Date: 29 February – 2 March, 2016
Venue: Prague, Czech Republic

2nd Asia Pacific course: paediatric neurometabolic and movement Disorders Date: 10- 12 June, 2016
Venue: Taipei, Taiwan

Metabolic myopathies course Date: 3-5 November, 2016
Venue: Paris, France

EMA workshop on pre-licencing activities
Date: 9 March, 2016
Venue: Barcelona, Spain

In collaboration with EMA, E-Rare will organize a workshop dedicated to Interactions between EMA and RD researchers on pre-licensing activities. The workshop will take place from 09:00 to 16:00 on the 9 of March 2015 in Barcelona, before the official start of the RE(ACT) meeting. It will be open to all researchers and interested stakeholders.

The places for Face-to-face meetings with EMA officers are limited! If you would like to participate, please send an email to juliane.halftermeyer@agencerecherche.fr for further instructions.

Genomics of Rare Diseases: Beyond the Exome
Date: 13-15 April, 2016
Venue: Cambridge, United Kingdom

Genomics of Rare Disease: Beyond the Exome will present an exciting blend of genomic science and clinical medicine. This conference provides an excellent forum for clinicians and scientists interested in human genomic variation and the mechanisms by which it exerts its phenotypic effects.
For further information

ExPRESS 2016 Expert Patient and Researcher EURORDIS Summer School
Date: 6-10 June, 2016
Venue: Barcelona, Spain

Patients are taking on ever increasing roles in advocating for medicines development, equal access to treatments across Europe and ensuring that medical information is clear, accurate and comprehensible. In order to help preparing them for these roles and as part of its commitment to empowering people living with rare diseases, EURORDIS launched its own training programme for expert patients in 2008.

The programme has online and face-to face components. The face-to-face portion trains 40 expert patients annually as part of an intensive 4.5 day course.
For further information

4th Rare Diseases Summer School
Date: 13 – 15 July, 2016
Venue: Zurich, Switzerland

The 4 radiz Rare Diseases Summer School will focus on a wide variety of subjects in the arena of rare diseases, from disease mechanisms and animal models, to improving diagnoses, to novel therapeutics. There will be lectures and workshops on drug development, model organisms, how to choose clinical endpoints, clinical trials, regulatory aspects, patient registries, patient initiated research, ethical considerations, as well as what rare diseases may tell us about common diseases. The application deadline is March 31 2016.
For further information


What's on Where?

MEET Symposium 2016
Date: 29-30 January, 2016
Venue: Nijmegen, The Netherlands

The Mitochondrial European Educational Training (MEET) Network presents: From bench to bedside, and back: Patients MEET Researchers.
For further information

Linking Life Science Data: Design to Implementation, and Beyond
Date: 18-19 February, 2016
Venue: Vienna, Austria

Open PHACTS will be hosting a two day conference which will include a variety of expert speakers and open discussions on linking data in the life sciences domain.
For further information

BPSU Rare Disease Conference 2016
Date: 23 February, 2016
Venue: Birmingham, United Kingdom

The conference will explore the theme ‘Rare disease in paediatrics – from birth to transition’. It will centre on the child's journey from diagnosis through transition and end of life care.
For further information

Multi-stakeholder symposium on improving patient access to rare disease therapies
Date: 24-25 February, 2016
Venue: Brussels, Belgium

EURORDIS and partners will bring together industry, patient leaders, academics, regulators and payers to discuss the current state of play and how to shape a more effective way to address value determination, appraisal, pricing and reimbursement of orphan medicines.
For further information

Clinical Innovation & Outsourcing
Date: 9-10 March, 2016
Venue: London, UK

Clinical Outsourcing & Partnering World is the largest industry event focusing on the strategic and operational considerations in clinical outsourcing. It is a place where serious business contacts are made. Attended by senior decision makers, it's a platform which facilitates meetings between your sales force and prospects and it's a cost effective sponsorship package with year round advantage.
For further information

The RE(ACT) Congress
Date: 9-10 March, 2016
Venue: Barcelona, Spain

The congress aims to bring together world leaders and young scientist from a variety of breaking through scientific field to present cutting edge research, to discuss results and to exchange ideas. Moreover, many patients and patient organization, which are committed in research, will be present to share their experience.
For further information

MYOLOGY 2016 Fifth International Congress of Myology
Date: 14-18 March, 2016
Venue: Lyon, France

Held for the first time in 2000, MYOLOGY has become a unique opportunity for international experts in the field to exchange and confront the emerging therapeutic approaches, but also to share the first clinical results. The science and medicine of muscle have reached a new milestone. In Myology 2016, no doubt there will be new results, new breakthroughs to share all together.
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

5th International Conference on Myelodysplastic Syndromes
Date: 14-16 April, 2016
Venue: Estoril, Portugal

For further information
8th Alstrom Syndrome International Conference
Date: 12-16 May, 2016
Venue: Massachusetts, USA

This international conference will have a scientific symposium for clinicians and researchers as well as sessions for parents, caretakers and patient organisations.
For further information

17th EMSOS Nurse and Allied professional Group Meeting
Date: 12-16 May, 2016
Venue: Massachusetts, USA

The meeting will be focussing on Ewing sarcoma, margins, pelvic tumours, targeted therapy; open sessions will offer the opportunity to report and discuss the latest results in all fields.
For further information

ECRD 2016 : The European Conference on Rare Diseases & Orphan Products
Date: 26-28 May, 2016
Venue: Edinburgh, United Kingdom

The ECRD is the only event which, from its small beginnings, has united all rare disease stakeholders from all European nations- patients and patient representatives, healthcare professionals and researchers, industry, payers, regulators and policy makers alike- in the fight against rare diseases. The ECRD now brings together over 80 speakers and more than 800 participants, covering six themes of content over two days: from the latest research, to developments in new treatments, to innovations in healthcare, social care and support at the European, national and regional levels.
For further information

FEPS 2016
Date: 13-14 July, 2016
Venue: Bonn, Germany

The symposium will be a privileged moment to demonstrate through various examples and discuss the pivotal role of Physiological sciences in the discoveries related to rare inherited diseases.
For further information

14th MPS Symposium
Date: 13-14 July, 2016
Venue: Bonn, Germany

In this symposium you get informed about the latest developments in research on the metabolic disease MPS and related lysosomal storage diseases. It is a great forum for discovering what is new in the field of metabolic diseases research.
For further information

European Association of Centres of Medical Ethics Conference
Date: 8 -10 September, 2016
Venue: Leuven, Belgium

The focus of this year’s conference is on a variety of highly relevant ethical issues in health care:
 Organizational Ethics in Health Care: Principles, Cases and Practical Solutions
 Ethical Issues in Care for Older Persons
 Ethical, Legal and Social Developments in Human Genomics
 Ethics and Integrity in Research
For further information

2nd International Conference on New Concepts in B Cell Malignancies
Date: 9-11 September, 2016
Venue: Estoril, Portugal

This conference aims at improving the understanding of the:
• principles and current developments of molecular pathogenesis of Bcell disorders
• the range of prognostic markers and their impact in specific clinical situations
• evolution of treatment principles in Bcell malignancies
• development of promising new agents targeting disease biology
• to improve understanding of key pathways driving expansion of normal vs. neoplastic Bcells
For further information

9th ISNS International meeting/10th ISNS European Regional meeting
Date: 11-14 September, 2016
Venue: The Hague, the Netherlands

The conference will aid the sharing of neonatal screening experiences for congenital metabolic disorders, its clinical diagnostics and follow-up, and will facilitate learning from other experiences. The programme will consist of plenary lectures, oral presentations and poster sessions and will be attractive for professionals, patient/advocacy groups, policy makers and industrial partners. The programme will include evaluation of performance of neonatal screening systems and strategies for improvement.
For further information

Rare metabolic disorders: detection, research, management and treatment
Date: 20-22 September, 2016
Venue: London, United Kingdom

This conference will discuss rare metabolic disorders, their detection, current research, disease management and treatment.
For further information

5th World Congress of Clinical Safety
Date: 21-23 September, 2016
Venue: Massachusetts, USA

The Boston Congress is organized by IARMM to improve and promote high advanced safe and clean science and technology. The congress covers a wide range of safety topics, such as clinical safety (patient safety, medication safety, medical device safety), infectious disease outbreak, disaster healthcare, clinical crisis governance, environmental helth & safety, food safety, and other related safety subjects.
For further information

ESID European Society for Immunodeficiencies: Biennial meeting
Date: 21-24 September, 2016
Venue: Barcelona, Spain

Sessions at this meeting will be devoted to understanding primary immunodeficiencies and their clinical aspects.
For further information

Commercial events

World Pharma Pricing and Market Access
Date: 23-24 February, 2016
Venue: London, United Kingdom

Conference with networking opportunities in the area of pharmaceutical pricing and access to drugs.
For further information

6th Annual World Orphan Drug Congress
Date: 21-22 April, 2016
Venue: Barcelona, Spain

Workshops range in topic from market forecasting to pricing & reimbursement, R&D, commercialization, marketing and treatment. You can choose from 8 half day workshops or 2 full-day seminars.
For further information


OrphaNews, The Newsletter of the Rare Diseases Community.
OrphaNews is supported by the European Commission's DG SANTE (RD-ACTION Joint Action N° 677024) and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Kate Bushby, Ana Rath
Editor: Divya Unni
Editors for Scientific Content: Sophie Höhn
Contact Us
Editorial Board: Valentina Bottarelli, Victoria Hedley, Yann LeCam, Stephen Lynn, Charlotte Rodwell, Domenica Taruscio, Ariane Weinmann Valentina Bottarelli, Victoria Hedley, Yann LeCam, Stephen Lynn, Charlotte Rodwell, Domenica Taruscio, Ariane Weinmann

Advisory Editorial Board: Ségolène Aymé, Anna Bucsics, Paul Boom, Bruno Dallapiccola, Jordi Llinares-Garcia, Adam Heathfield, Alastair Kent, Dominique Péton-Klein, Milan Macek, Till Voigtländer

Orphanet Partner Country Representatives: Romi Armando (Argentina), Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Micheil Innes (Canada), Ingeborg Barisic (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Sirpa Ala-Mello (Finland), Joerg Schmidtke (Germany), 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), Dorra H'mida (Tunisia), Ugur Ozbek (Turkey), Dian Donnai (UK)
Orphanet - All rights reserved
Disclaimer : This presentation is part of the project / joint action N° 677024 / RD-ACTION' which has received funding from the European Union's Health Programme (2014-2020).

Photo credit : Serimedis http://www.serimedis.inserm.fr/ (unless otherwise stated)