21 December 2012 print
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Contribute to the public consultation on the criteria for the European Reference Networks launched by the European Commission

The European Commission has launched a public consultation on the criteria for the European Reference Networks and healthcare providers wishing to join the network under the framework of article 12 of the Directive on cross-border healthcare (Directive 2011/24/EU). A conceptual paper and a questionnaire have been prepared by Directorate General Health & Consumers.
European Reference Networks are of particular relevance in the field of rare diseases which are mentioned in the Directive as an example of a field of particular need for such networks.
The Directive on the application of patients' rights in cross-border healthcare requires the European Commission to support Member States in the development of European Reference Networks between healthcare providers and centres of expertise. The main added value of the European Reference Networks and of the Centres of Expertise is to facilitate improvements in access to diagnosis and delivery of high-quality, accessible and cost-effective healthcare in the case of patients who have a medical condition requiring a particular concentration of expertise or resources, particularly in medical domains where expertise is rare (see Recital 54 of the Directive). European Reference Networks could also be focal points for medical training and research, information dissemination and evaluation, especially for rare diseases. Article 12 requires the Commission to adopt a list of criteria that the networks must fulfill, as well as the conditions and criteria which providers wishing to join networks must fulfill. The Commission is also required to develop and publish criteria for establishing and evaluating European Reference Networks: the Commission must also facilitate the exchange of information and expertise on the establishment of the networks and of their evaluation.
The following target groups are encouraged to give their views:

  • Patient organisations, health professionals' organisations and healthcare provider's organisations.
  • Healthcare providers and centres of excellence, academic and public health and healthcare specialised institutions.
  • Public authorities and government-appointed bodies responsible or involved in the definition of criteria and the establishment and evaluation of centres of reference/excellence and reference networks of centres providing highly specialised healthcare
The aim of the consultation is to receive input and opinion of stakeholders based on evaluated experiences, regional or national models, technical and professional standards, existing criteria or recommendations, needs and feasibility and EU added value.
The deadline for the consultation is 22 February 2013.

Learn more about the on-line consultation

EUCERD update
Warm holiday wishes from the European Union Committee of Experts on Rare Diseases

Summary report of the Sixth Meeting of the EUCERD now available online

The European Union Committee of Experts on Rare Diseases (EUCERD) met for the sixth time on 14-15 November 2012. The two-day meeting was the opportunity to tackle a number of priority subjects, including the elaboration of the EUCERD Recommendations on European Reference Networks for Rare Diseases, and the proposal from the European Commission to create an EU platform for rare disease registration. Other topics for discussion included the outcomes to date of the EUCERD Joint Action and future planned activities, possible areas of collaboration at EU-level in the field of newborn screening, progress towards the elaboration and implementation of national plans/strategies for rare diseases in the EU Member States, and plans for Rare Disease Day 2013 (28 February 2013).
The meeting was preceeded by a workshop on rare disease registries organised in the context of the EUCERD Joint Action which aimed to share the latest developments in the field and yielded a number of discussions on how to achieve optimum harmonisation and cooperation.
The public summary report of the 6th Meeting of the EUCERD is now available online.


EU Policy News

European Commission approves gene therapy: a first of its kind in the European Union, US and Canada

On 2nd November, 2012, the European Commission announced the authorisation of Glybera (alipogene tiparvovec) for marketing in the European Union. The drug, developed by the Dutch company UniQure, is intended to treat patients with lipoprotein lipase deficiency (LPLD), a very rare inherited disorder which disrupts fat production in the body. Due to a defective gene, patients with this disorder cannot produce enough lipoprotein lipase (LPL), an enzyme responsible for breaking down fats. Glybera uses an adeno-associated virus to infect muscle cells with working copies of the LPL gene to enable production of the enzyme in the cells. Backed by the recommendation of the European Medicines Agency, this is the first regulatory approval of a gene therapy drug in the European Union, US and Canada.

Press release of UniQure
European Commission register of medicinal products


National & International Policy Developments
Other European news
France’s 26th Telethon raises 81,065,239 Euros

In the context of the present economic crisis, a concerted national effort helped raise over 81 million Euros during the 26th edition of the Telethon, which took place over the weekend of 8-9 December. However, the AFM (Association Française contre les Myopathies) has urged people to continue donating towards the cause. In a press release, Laurence Tiennot-Herment, president of the AFM-Telethon said, “We are now calling on all those who can and who have not yet done so to join this great movement to enhance this result that we can all be proud of. Twenty-five years ago we had a dream and while this dream is becoming a reality, we know that we owe it to an audacious and united France, the foundation of our battle and the driving force behind our future victories.

France’s National Cancer Institute publishes activity report on rare cancers for 2011

The National Cancer Institute (INCa) of France has published its second report (available in French) on the management of adult patients with rare cancers. It focuses on the activities of the 15 national centres of expertise and includes an analysis of those of 4 anatomopathological networks. The report aims to better evaluate the system and improve the quality of patient care. INCa has also published a report (available in French) on the time delay between diagnosis and treatment initiation of certain cancers, with the help of 10 national cancer registries.

4th Rare Disease Day in Finland

Swedish Orphan Biovitrum Finland organised the 4th Harvinaiset Sairaudet–päivä (Rare Disease Day) together with stakeholders in Helsinki on 19 October 2012. This day provided a forum for questions concerning research and management for Finnish decision-makers and specialists.The principal goal of the day was to discuss how Finland would become a model country for rare disease research and management and which actions would ensure that patients suffering from rare conditions would be entitled to the same quality of treatment as other patients. The meeting was chaired by MD. Riitta Salonen, Orphanet country coordinator from the Department of the Medical Genetics,Väestöliitto.

Other International News
FORGE: A successful Canadian project to identify genes causing rare paediatric disorders

FORGE (Finding of Rare Disease Genes) Canada is a national consortium of clinicians and scientists using new sequencing technology to rapidly identify genes responsible for rare genetic disorders that affect children in Canada and throughout the world. Launched in April 2011, the project has for objectives to: “1) Assist doctors to identify patients with rare childhood diseases. 2) Sequence the genomes of patients to identify disease-causing genetic changes. 3) Set up a national data coordination centre to streamline and improve existing large-scale sequence analysis tools. 4) Create national ethical guidelines for analyzing sequence data from entire genomes and for sharing results with families.” By November 2012, FORGE had discovered 41 novel genes previously not linked to a human disease.

Consult the FORGE website

Guidance Documents and Recommendations
New Spanish guide for Spasmodic Dysphonia (Laryngeal dyskinesia)

The Spanish Association of Spasmodic Dysphonia has recently published the “Information Guide for patients and professionals of spasmodic dysphonia”. The document, only available in Spanish language, offers an approach to the disease from several points of view: primary care, otolaryngology, neurology, speech therapy, and psychology.

Association Website

Bioinformatics, Registries and Data Management

US National Registry for Ichthyosis and Related Disorders to cease functioning after 2012 due to lack of funding…

Philip Fleckman, principal investigator of the US National Registry for Ichthyosis and Related Disorders, announces, in the Journal of Investigative Dermatology, that the Registry, in existence since 1994, will cease functioning after 2012. Funded by NIH (National Institutes of Health) and FIRST (Foundation for Ichthyosis and Related Skin Types), it was set up to “improve understanding of the diagnosis, pathophysiology, and treatment of the ichthyoses.” For the last 11 years, it was instrumental in providing important epidemiological data. The Registry continued in maintenance mode after funding ceased from NIH in 2004 and will stop operating after funding stops from FIRST at the end of 2012. Fleckman points out that “investigators who wish to utilise the Registry should contact the principal investigator via the website (…) in order to take advantage of this unique source while it is available”.

Consult the full article

… Stakeholders consider whether patient organisations and companies could fund patient registries

As part of the commentaries on the announcement of the closure of the National Registry for Ichthyosis and Related Disorders, the authors of another article appearing in the same issue of the Journal of Investigative Dermatology explain the importance of patient registries for rare dermatological disorders. Arguing that such registries are “important sources of data for researchers, clinicians and patients”, the authors propose patient organisations, rare disease advocacy groups and companies as funding options for their sustenance. They also mention the efforts of Orphanet, NORD (National Organization for Rare Disorders), EURORDIS (the European Organisation for Rare Diseases) and ORDR (Office of Rare Diseases Research, National Institutes of Health) in unifying “the existing, disparate registries for rare disorders, and, where none exist, to set up a single, broadly accessible registry for specific disorders”.

Consult the PubMed abstract

Spanish database for rare diabetes syndromes launched

In November, this year, the EURO-WABB project - the EU Rare Diseases Registry for Wolfram syndrome, Alström syndrome, Bardet-Biedl syndrome and other rare diabetes syndromes - announced the launch of the Spanish rare diabetic syndromes database. The registry, called Spanish Registry of Wolfram, Alström and Bardet-Biedl Syndromes (REWBA), is open to patients, doctors, sanitary professionals and researchers to participate and aims at collecting information about these three rare diabetes syndromes in order to foster their study in Spain.

Consult the EURO-WABB press release

European Medicines Agency publishes report on access to clinical-trial data and transparency workshop

The European Medicines Agency announces, in a press release, the publication of a report that highlights “the outcomes of the workshop on access to clinical trial data and transparency, which was hosted at the Agency on 22 November 2012”. The report presents the debate that was at the heart of the clinical-trial transparency event, and also outlines the Agency’s action plan with regard to access to clinical-trial data. It can be consulted on the webpage of the press release.

Screening and Testing
Genetic testing in sperm banks could identify “safer” matches for donors and clients

An article published in Science magazine talks about an American company called GenePeeks, which is in the news for its genetic analysis service that would “predict disease risk in hypothetical children based on the DNA of prospective parents.” The company headed by Lee Silver, geneticist and Anne Morris, who used a sperm donor to conceive her child, will partner with sperm banks and would offer clients the genetic service that can show how donor DNA would combine with the recipient’s DNA. Morris, whose son was born with MCAD deficiency, - a rare recessive disorder in which both parents carry a disease mutation -, thinks that the expanded testing “will help others avoid her family’s fate”.

Consult the abstract

Europe needs competent bodies responsible for quality assurance of its genetic services

Two articles in the November 2012 issue of the European Journal of Human Genetics talk about the quality of existing genetic testing services in Europe. A survey conducted by Sarah Berwouts et al gives the state of the art on “what is in place or lacking in the diagnostic labs to guarantee good performance”. Using the Orphanet registry of molecular labs which provides information on quality assurance in collaboration with EuroGentest, the survey contacted 31 European countries and studied the case of 291 laboratories that responded. According to the authors of both articles, the results show, that despite increasing awareness on the part of the laboratories regarding accreditation, there is much scope for improvement. They conclude that “quality practices vary widely in European genetic testing laboratories” which can lead “to a potentially dangerous situation in which the quality of genetic testing is not consistently assured” and propose that the data of the survey “should be used by all geneticists to convince their authorities that (more) European initiatives for genetic quality services” are needed.

The Council of Europe publishes a general readership brochure comprising objective information on genetic testing

The Council of Europe, with the support of the European Society of Human Genetics and EuroGentest, has come up with an information document that aims to “provide objective information on genetic tests, their nature and potential implications of their results". The document also presents different types of tests available, their application in the medical field and the extent and limits” of the test results. The document can be consulted, in English or in French, online on the website of EuroGentest. It will be translated into twenty European languages.

EASAC and FEAM publish the first Working Group report on consumer genetic services in Europe

A lay account of the latest report of EASAC - the European Academies Science Advisory Council, and FEAM - the Federation of European Academies of Medicine, entitled "Direct-to-Consumer genetic testing for health-related purposes in the European Union" has been published. It is a non-technical summary of the report of the Working Group that was set up by EASAC and FEAM to review consumer genetic services in Europe. The report proposes a “list of recommendations to policy-makers in the European Commission, European Parliament and Council of Ministers, and to Member States in which parallel action may be necessary”.

Consult the summary
Consult the full report


Ethical, Legal & Social Issues

Pre-existing concerns of discrimination have an important role in justifying the non-uptake of genetic testing

In an article appearing in the European Journal of Human Genetics, the authors discuss how genetic discrimination affects people’s attitude toward genetic testing. Despite existing genetic non-discrimination acts in many countries in Europe and in the USA, fears of being discriminated against by insuring companies and by one’s employers, following genetic testing, still persist. The article tries to bring to light the nature and the cause of these fears. According to the authors, who studied the case of six Dutch families involved in genetic testing for hypertrophic cardiomyopahy (HCM), “the fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members.” The results of their study indicate that these “pre-existing concerns of discrimination have an important role in justifying the non-uptake of genetic testing”.

Consult the PubMed abstract


Orphanet News
Orphanet Journal of Rare Diseases supplement focuses on the proceedings of the Sixth European Conference on Rare Diseases and Orphan Products

In its second supplementary issue, Orphanet Journal of Rare Diseases has published the meeting abstracts of the 6th European Conference on Rare Diseases and Orphan Products that took place in Brussels, Belgium in May this year. Among the highlights are discussions on state of the art on rare diseases in Europe and around the world, various national strategies for rare diseases, including French and Belgian experiences, as well as presentations on the scope of centres of expertise for rare diseases, different research considerations, particularly using web semantics, orphan medicinal products and health technology assessment, genetic testing and classification of rare diseases. The OJRD is an open access electronic publication.

Consult the OJRD supplementary issue


New Syndromes

Lethal syndromic vasculopathy associated with a mutation in FBLN4 impairing elastogenesis

The authors characterised a syndrome of lethal arteriopathy from the examination of 22 unrelated infants from South India, eight having a history of consanguinity. The disease was detected at a median age of 1.75 month (1 day to 15.5 months), from a cardiorespiratory distress in all but two cases identified from an incidentally discovered murmur. Striking cardiovascular findings are aneurysmal dilatation, elongation, tortuosity and narrowing of the aorta, pulmonary artery and their branches. The phenotype includes characteristic facial features, i.e. long philtrum and thin vermillion observed in 90 %; hypertelorism (57 %), micrognathia (43 %), prominent eyes (43 %), sagging cheeks (43 %), high arched palate (38 %), hooded eyelids (29 %), broad forehead (29 %) and dysplastic/low set pinnae (19 %). Other clinical signs also observed are cutis laxa (52 %), long slender digits (48 %), generalized hypotonia (43 %), visible arterial pulsations (38 %), joint laxity (27%), herniae and seizures (19 %). Delay in gross motor milestones is noted in all children older than 4 months. Skin biopsy shows deficient and fragmented elastic fibers in the subcutaneous layers and the FBLN4 mutation found in all patients emphasizes the critical role of fibulin-4 in elastogenesis. One infant is compound heterozygous for this mutation, the other 21 being homozygous. This latter status is associated with high mortality rate as 17 of these 21 patients died at a median age of 4 months.

Consult the PubMed abstract

Orphanet J Rare Dis ; 61 ; 3 September 2012
A potentially treatable form of autism associated with epilepsy and intellectual disability

The authors have identified in two consanguineous families a Mendelian form of autism associated with epilepsy and intellectual disability. Two inactivating BCKDK mutations, namely one in each family, have been discerned in the affected individuals. These ones display a decrease of plasma branched chain amino acids (BCAAs) likely resulting from a negative regulation of the BCKDH complex whose E1-α subunit is inactivated by phosphorylation performed by the Bckdk kinase. Bckdk knockout mice exhibit the same profile that can be reverse by dietary supplementation with BCAAs.

Consult the PubMed abstract

Science ; 394-7 ; 19 October 2012
A male-male transmission of a novel pleiotropic sclerosing bone dysplasia syndrome

Examining a father and his 4-year-old son, the authors collected clinical, radiological and genetic data consistent with the diagnosis of a novel pleiotropic sclerosing bone dysplasia syndrome. These two patients have the same facial dysmorphic features (hypertelorism, prominent forehead, and wide nasal bridge), macrocephaly, hearing loss, cleft palate, developmental delay, hypotonia and osseous anomalies like marked cranial sclerosis and sclerosis of the ribs and long bones, which evolved in severity in the son, between the ages of 2 and 4 years. The father’s radiographs exhibit prominent coarse striations, patchy metaphyseal sclerotic plaques, markedly increased bone density, cortical thickening of long bones, and significant degenerative changes in the thoracic spine. The son suffers from sleep apnea resulting from multi-level airway obstruction due to adenoid hypertrophy, lingual tonsil hypertrophy, subglottic stenosis, and supra-arytenoid tissue consistent with laryngomalacia and tracheomalacia. According to the authors, this phenotype resembles but is different from those of mixed sclerosing bone dysplasia (MSBD) and osteopathia striata with cranial sclerosis (OS–CS). Given that the mother and the daughter of this family are healthy, a male-male transmission seems evident.

Consult the PubMed abstract

Am J Med Genet A ; 2292-6 ; 10 September
Congenital heart defect, mild ichthyosis and hypogonadotropic hypogonadism associated with a novel Xp duplication

A novel Xp duplication has been identified by the authors in a 20-year-old man and his 6-year-old half-brother. Both have the same phenotype, i.e. congenital heart defect (atrial septal defect, in addition the elder had an aortic root dilatation), developmental delay, minor anomalies ichthyosis (dry scaly skin and varicose veins), hypogonadotropic hypogonadism, and particular facial features (short forehead, short nose, prominent ears). Small uvula, short fingers with camptodactyly, generalized muscle wasting, duplex kidney on one side and urinary bladder diverticulum are also observed in the older brother. Given the complexity of this phenotype and that it is consistent with mutations in genes located in the duplicated region, the authors incline towards a relationship between this clinical entity and this Xp anomaly.

Consult the PubMed abstract

Am J Med Genet A ; 2342-6 ; September 2012
A novel autosomal dominant inclusion body myopathy linked to 7q22.1-31.1

The authors report on a new autosomal dominant hereditary inclusion body myopathy (HIBM) detected in 16 members of a Chinese family. The disease occurs between the third and fifth decade. Age of onset of affected male individuals is earlier than that of affected women. The muscle weakness reaches at first hip girdle, neck flexors and axial musculature, and then shoulder girdle. The disability progresses slowly towards a moderate muscle atrophy in the advanced stages so that the patients’ condition remains relatively benign. Muscle biopsies reveal necrotic, regenerating, and rimmed vacuolated fibers. Congophilic inclusions are also present in some fibers. Genetic analysis detected a critical locus containing 65 genes on chromosome 7q22.1-31.1. According to the authors, this phenotype doesn’t match any known HIBM so they suggest to list it as HIBM4.

Consult the PubMed abstract

PLoS One ; 2012
Preaxial anomalies of the upper limbs in a family with a novel mutation in the ZRS sequence

The authors examined five members of a nonconsanguineous family affected by variable preaxial anomalies of the upper limbs encompasssing isolated triphalangeal thumb, preaxial polydactyly, preaxial syndactyly, and absent thumb and radius. Cardiac and renal defects (atrial septal defect, small patent ductus arteriosus and absent left kidney) are also observed in one affected member as well as absent right kidney in another one. This phenotype resembles that of Townes-Brocks syndrome but the SALL1 mutation responsible for this pathology is not present in these five patients. On the other hand they all carry a novel mutation in the ZRS sequence, located within intron 5 of LMBR1 gene, and that regulates SHH expression. SHH is also known to interact with SALL1 and this relationship may explain the similarities between Townes-Brocks syndrome manifestations and the anomalies affecting this family.

Consult the PubMed abstract

Am J Med Genet A ; 2610-5 ; October 2012
A new channelopathy including intellectual disability, cardiac defects and seizures resulting from a CLIC2 mutation

In search of a new X-linked intellectual disability gene, the authors have identified a CLIC2 mutation in two brothers suffering from profound intellectual disability, cardiac defects appearing in their fourth decade (cardiomegaly, congestive heart failure in both cases, and atrial fibrillation in one), seizures, and large joint contractures. They have large ears and testes, and abnormal positioning of the thumbs. One brother also presents with hydrocephalus. As the CLIC2 mutation detected here results in an enhancement of ryanodine receptor channel activity, the authors think that they are facing a new channelopathy.

Consult the PubMed abstract

Hum Mol Genet ; 4497-507 ; 15 October 2012
An ncRNA involved in a syndrome of primordial dwarfism, intellectual deficiency, and facial dysmorphism

The authors have identified an apparently novel form of syndromic primordial dwarfism associated with intellectual deficiency and distinct facial features in a family whose affected members are born to consanguineous parents. The facial characteristics observed in these patients are triangular face, narrow and short palpebral fissure, deep-seated eyes, sparse eyebrows, low set ears, malar hypoplasia, broad nose, short philtrum, wide mouth, full lips, widely spaced teeth, macrostomia, and strabismus. Other clinical signals listed include scoliosis, mild epiphyseal changes in the proximal phalanges, short Achilles’ tendons, and thickened skin over the hands and feet. A LARP7 mutation segregating with this disease has been identified. The resulting depletion of 7SK ncRNA extends the list of molecular mechanisms involved in primordial dwarfism.

Consult the PubMed abstract

Hum Mutat ; 1429-34 ; October 2012
Congenital muscular hypertrophy and liver enlargement in two brothers with 7q36.3 duplication

The authors report on two pregnancies occuring in the same family and presenting with similar findings on fetal ultrasonography, i.e. muscular hypertrophy on extremities (and of the trunk in one case), liver enlargement and polyhydramnios. One pregnancy was terminated and the boy born at the end of the second pregnancy has mild psychomotor development delay, small external genitals with cryptorchidism. An examination performed at 24 months mentions edema on the dorsal sides of his hands and feet, and particular facial characteristics (prominent forehead, hypertelorism, flat nasal bridge, short columella, smooth philtrum, and hypertrophic and protruding tongue). A duplication of 7q36.3 including the SHH gene has been identified in both children and the authors hypothesize that this genetic anomaly may result in overexpression of SHH inducing this clinical features.

Consult the PubMed abstract

Eur J Med Genet ; 557-60 ; October 2012

New Genes

Congenital disorder of glycosylation: novel pathogenic mutations identified in ALG13 and PGM1 genes
Consult the PubMed abstract
To read more about "Congenital disorder of glycosylation"

Hum Mol Genet ; 4151-61 ; 1 October 2012
Spinocerebellar ataxia type 29: a mutation identified in ITPR1 already known to be involved in spinocerebellar ataxia type 15
Consult the PubMed abstract
To read more about "Spinocerebellar ataxia type 29"

Orphanet J Rare Dis ; 67 ; 17 September 2012
Alpers syndrome: FARS2 mutations induce a fatal infantile form and establish a new genetic cause altering tRNA activity
Consult the PubMed abstract
To read more about "Alpers syndrome"

Hum Mol Genet ; 4521-9 ; 15 October 2012
Neural tube defect: DACT1 mutations emphasizes the role of planar cell polarity genes
Consult the PubMed abstract
To read more about "Neural tube defect"

Hum Mutat ; 1450-5 ; October 2012
Lethal congenital contracture syndrome: an homozygous MYBPC1 mutation more harmful than heterozygous missense MYBPC1 mutations previously found
Consult the PubMed abstract
Hum Mutat ; 1435-8 ; October 2012
Methylmalonic acidemia with homocystinuria: mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism mimicking cblF defect
Consult the PubMed abstract
To read more about "Methylmalonic acidemia with homocystinuria, type cblF"

Nat Genet ; 1152-5 ; October 2012
Neuroblastoma: HACE1 and LIN28B variants influencing susceptibility to the disease and its progression
Consult the PubMed abstract
To read more about "Neuroblastoma"

Nat Genet ; 1126-30 ; October 2012
Axonal neuropathy with neuromyotonia: loss-of-function mutations in HINT1 cause an autosomal recessive neuropathy forming a disease entity
Consult the PubMed abstract
Nat Genet ; 1080-3 ; October 2012
Disseminated superficial actinic porokeratosis: heterozygous MVK mutations induce very diverse clinical manifestations
Consult the PubMed abstract
To read more about "Disseminated superficial actinic porokeratosis"

Nat Genet ; 1156-60 ; October 2012
Mendelian susceptibility to mycobacterial diseases: a role of ISG15 mutations through impaired IFN-ɣ immunity
Consult the PubMed abstract
To read more about "Mendelian susceptibility to mycobacterial diseases"

Science ; 1684-8 ; 28 September 2012

Research in Action

Fundamental Research
Proximal spinal muscular atrophy: a novel series of mouse models mimicking phenotypes with a range in disease severity
Consult the PubMed abstract
To read more about "Proximal spinal muscular atrophy"

Hum Mol Genet ; 4431-47 ; 15 October 2012
Duchenne muscular dystrophy: preventing phosphorylation of dystroglycan, and thus may be its degradation, ameliorates the dystrophic phenotype
Consult the PubMed abstract
To read more about "Duchenne muscular dystrophy"

Hum Mol Genet ; 4508-20 ; 15 October 2012
Myelodysplastic syndromes: a potent tumor suppressor function for de-ubiquitinating enzyme BAP1 identified
Consult the PubMed abstract
To read more about "Myelodysplastic syndromes"

Science ; 1541-6 ; 21 September 2012
Sandhoff disease: creation of two inducible strains of mice allowing modulation of β-hexosaminidase expression over time
Consult the PubMed abstract
To read more about "Sandhoff disease"

PLoS Genet ; September 2012
Clinical Research
Hemophilia B: a novel recombinant fusion protein controlling coagulation with less frequent intravenous injections
Consult the PubMed abstract
To read more about "Hemophilia B"

Blood ; 2405-11 ; 20 September 2012
An adjuvant chemotherapy showing no benefit in relapse-free survival or overall survival on resected high-risk soft-tissue sarcomas

Consult this study on Orphanet
Consult the PubMed abstract

To read more about "Soft tissue sarcoma"

Lancet Oncol ; 1045-1054 ; October 2012
Renal cell carcinoma: regorafenib has antitumour activity with side effects as first-line treatment for metastatic or unresectable tumors
Consult the PubMed abstract
To read more about "Renal cell carcinoma"

Lancet Oncol ; 1055-62 ; October 2012
Hutchinson-Gilford progeria syndrome: lonafarnib may improve the rate of weight gain, cardiovascular status, bone structure, or audiological function
Consult the PubMed abstract
To read more about "Hutchinson-Gilford progeria syndrome"

Proc Natl Acad Sci U S A ; 16666-71 ; 9 October 2012
Fragile X syndrome: GABAB receptor agonists improve symptoms in both mice and humans
Consult the PubMed abstracts
To read more about "Fragile X syndrome"

Sci Transl Med ; 19 September 2012
Congenital heart block: high prevalence of conduction anomalies found in ECG of parents of affected children suggests an heritable trait
Consult the PubMed abstract
To read more about "Congenital heart block"

Circulation ; 1469-77 ; 18 September 2012
Pediatric sarcomas: from molecular mechanisms to novel therapeutic possibilities
Consult the PubMed abstract
Pediatr Res ; 112-21 ; August 2012
West-Nile encephalitis: long term follow-up of patients with WNV infection shows high prevalence of mild chronic kidney disease
Consult the PubMed abstract
To read more about "West-Nile encephalitis"

PLoS One ; 2012
Tetralogy of Fallot: 1q21.1 duplications and other rare copy number changes suggest novel pathogenetic mechanisms
Consult the PubMed abstract
To read more about "Tetralogy of Fallot"

PLoS Genet ; August 2012
Telomere dysfunction: a spectrum defined by the short telomere defect
Consult the PubMed abstract
Nat Rev Genet ; 693-704 ; October 2012
Stem Cells

Stem Cell Therapeutics: Still a long way to go

An article published in Cell Stem Cell revisits the promising but challenging domain of stem cell therapeutics. The author specifically speaks about the hurdles that need to be overcome before “novel stem cell therapies can achieve meaningful clinical impact”. He points out that although stem cells could be a promising source for new therapies, they might take decades to mature, as do all new therapeutics: “Fifty years after the first attempts at HSC (Hematopoietic stem cell) transplantation, and even with all the improved understanding we now have of both HSCs and immunological mismatch, our success rates are still woefully inadequate. (…) Realistically, we should anticipate that new therapies based on stem cells for other tissues will likewise take decades to mature. In the short term, there will probably be more failures than successes, and one can only hope that the new field of regenerative medicine can learn the lessons of the past and proceed with prudence and caution.

Consult the PubMed abstract

Gene Therapy
Retinitis pigmentosa: subretinal gene transfer restores vision and delays retinal degeneration in mouse model
Consult the PubMed abstract
Hum Mol Genet ; 4486-96 ; 15 October 2012
Niemann-Pick disease type A: efficient intracranial AAV-mediated enzyme augmentation therapy in mouse and primates
Consult the PubMed abstract
To read more about "Niemann-Pick disease type A"

Mol Ther ; 1893-901 ; October 2012
Severe combined immunodeficiency, alymphocytotic type: immune functions corrected by lentiviral transfer of codon-optimized gene
Consult the PubMed abstract
To read more about "Severe combined immunodeficiency due to DCLRE1C deficiency"

Mol Ther ; 1968-80 ; October 2012
Argininemia: long-term survival with gene transfer correcting enzyme deficiency in a neonatal murin model
Consult the PubMed abstract
To read more about "Argininemia"

Mol Ther ; 1844-51 ; October 2012
Therapeutic Approaches
Blackfan-Diamond disease and myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality: L-leucine alleviates anemia in animal models
Consult the PubMed abstracts
To read more about "Blackfan-Diamond disease"
To read more about "Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality"

Blood ; 2214-24 ; 13 September 2012
Non-syndromic retinal ciliopathies: from genetic anomalies to therapy

One-third of non-syndromic retinal dystrophies is linked to a defect in a ciliary protein. This article reviews gene defects, vertebrate models, and translational research – mainly gene augmentation therapies – for non-syndromic retinal ciliopathies.

Consult the PubMed abstract

To read more about "Retinitis pigmentosa"
To read more about "Progressive cone dystrophy"
To read more about "Cone rod dystrophy"
To read more about "Genetic macular dystrophy"
To read more about "Leber congenital amaurosis"

Hum Mol Genet ; 15 October 2012
Glycogen storage disease due to acid maltase deficiency: anti-CD3 antibodies induce immune tolerance to enzyme replacement therapy
Consult the PubMed abstract
To read more about "Glycogen storage disease due to acid maltase deficiency"

Mol Ther ; 1924-31 ; October 2012
Fragile X syndrome: pharmacological enhancement of endocannabinoid signalling corrects behavioural abnormalities in mouse
Consult the PubMed abstract
To read more about "Fragile X syndrome"

Nat Commun ; 25 September 2012
Dravet syndrome: Scn1a+/- mice have autism behavior due to impaired GABAergic neurotransmission that can be treated
Consult the PubMed abstract
To read more about "Dravet syndrome"

Nature ; 385-90 ; 20 September 2012
Diagnostic Approaches

Congenital myasthenic syndromes: an analysis of the contribution of genetic testing
Consult the PubMed abstract
To read more about "Congenital myasthenic syndromes"

Hum Mutat ; 1474-84 ; October 2012
Fluorescence imaging of mitochondrial membrane potential in cultured skin fibroblasts is a useful method for the evaluation of OXPHOS functioning
Consult the PubMed abstract
Pediatr Res ; 232-40 ; September 2012

Patient Management and Therapy

Lemierre syndrome: a review from a case caused by Fusobacterium necrophorum
Consult the PubMed abstract
Lancet Infect Dis ; 808-15 ; October 2012
Kleine-Levin syndrome: update about a disorder at the interface of neurology and psychiatry
Consult the PubMed abstract
To read more about "Kleine-Levin syndrome"

Lancet Neurol ; 918-28 ; October 2012
Myotonic dystrophies: molecular, clinical, and therapeutic challenges
Consult the PubMed abstract
To read more about "Steinert myotonic dystrophy"
To read more about "Proximal myotonic myopathy"

Lancet Neurol ; 891-905 ; October 2012
Reversible cerebral vasoconstriction syndrome: unknown pathological process, easy diagnostic and no proven treatment available
Consult the PubMed abstract
Lancet Neurol ; 906-17 ; October 2012
Alkaptonuria Society announces the launch of “DevelopAKUre Clinical Trials”

The AKU Society pre-announced the launch of clinical trials to assess the use of the drug nitisinone in AKU patients in collaboration with the Royal Liverpool University Hospital. The project, to start in 2013, will be funded through a grant from the European Commission. The clinical trials will involve centres in the UK (Liverpool), France (Paris) and Slovakia (Piestany).

For further details


Orphan Drugs

Taking orphan drug development further

The authors of an open access article appearing in Expert Review of Pharmacoeconomics & Outcomes Research discuss the development of drugs for rare diseases – the progresses made till now and the needs to be addressed in future. They provide an overview of what more could be done to “promote innovative ways to ensure drug availability” through different support structures in research, development and regulations, in addition to existing initiatives, at European or global level (E-rare, IRDiRC).

Consult the full article

New pathway, in which manufacturers receive grants and accept pricing caps, could stimulate development of ultra-orphan drugs

In an article appearing in Health and Affairs, the authors propose a new “pathway” that has the “potential to foster innovation for ultra-orphan” drugs (an ultra-orphan drug being, according to the authors, one that is intended for conditions affecting no more than one in every 10,000 people). The “grant-and-access” pathway, in which access refers to patients’ access to affordable drugs, would “lower the economic barriers for early-phase drug development. (…) Companies applying for orphan drug designation could simultaneously apply to a special grant pool within the FDA (US Food and Drug Association) or the National Institutes of Health, which would be designed to largely offset clinical development costs” and the companies would also accept price caps “based on how long drug development took and how much it cost, expected market size, and the target internal rate of return.

Consult the PubMed abstract

Licencing agreement between Recordati and Erytech for Graspa® commercialisation

In November, this year, the Italian pharmaceutical company, Recordati announced that it has entered into an agreement with Erytech Pharma, a French development-stage biopharmaceutical company, granting Recordati’s subsidiary Orphan Europe exclusive rights for the commercialisation and distribution of Graspa® (human erythrocytes encapsulating L-asparaginase) for the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in Europe. Graspa® has obtained an orphan drug designation in Europe and in the USA for ALL.

Consult the Recordati press release

Cystic fibrosis in an era of genomically guided therapy
Consult the PubMed abstract
To read more about "Cystic fibrosis"

Hum Mol Genet ; 66-71 ; 15 October 2012
Regulatory News
13 positive opinions recommending orphan designation at the December COMP meeting

The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 13 positive opinions recommending orphan designation at the December 2012 COMP meeting for the treatment of:

  • familial adenomatous polyposis
  • growth hormone deficiency
  • glioma
  • mucopolysaccharidosis type IIIB (Sanfilippo B syndrome)
  • 5q spinal muscular atrophy
  • beta-thalassaemia intermedia and major
  • ovarian cancer
  • Wilson’s disease
  • retinitis pigmentosa
  • follicular lymphoma
  • achondroplasia
  • pancreatic cancer
  • systemic sclerosis
Consult the European Register of Designated Orphan Medicinal Products
Consult the Orphanet list of orphan drugs authorised for marketing in Europe



E-Rare launches 5th Joint Transnational Call for Research Projects on Rare Diseases (JTC 2013)

On the 7th of December 2012, E-Rare, a European programme for research on rare diseases, opened its 5th Joint Transnational Call for Research Projects on Rare Diseases (JTC 2013). The aim of the call is to enable scientists in different countries to build an effective collaboration on a common interdisciplinary research project based on complementarities and sharing of expertise, with a clear translational research approach.

For further details


Courses & Educational Initiatives

European Cytogeneticists Association Courses

The European Advanced Postgraduate Course in Classical and Molecular Cytogenetics 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. Information for the 2013 course is now available.

For further details

Online Master of Science in Haemoglobinopathy

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

For further details

The European School of Haematology distance learning tools

The European School of Haematology (ESH) is a non-profit organisation founded in 1986. Its mission is continuous medical education in Haematology and the fields related to Haematology. ESH organises conferences throughout Europe and on other continents. It also produces distance learning tools of which many are freely available on the ESH website: These include: The Curriculum on Iron Metabolism and Related Disorders: This is a comprehensive curriculum comprising webcasted lectures, videos, interviews, round table discussions etc. The faculty is composed of distinguished international experts in the field. Webcasted conferences are also freely available on the website, including topics such as: Diagnosis and Management of Rare Anaemias; Haemoglobin Disorders: Laboratory Diagnosis and Clinical Management; World Cord Blood Congress, and more.

Goldrain Courses in Clinical Cytogenetics and Prenatal Genetic Diagnosis

The Goldrain Prenatal Genetic Diagnosis, tentatively course scheduled from 6-12 October 2013 at the Goldrain Castle in South Tyrol (Italy), is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination.

For further details

Orphan Academy 2012 Programme

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

For further details

EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops

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

For further details


What's on Where?

Save the date! 1st Conference of the International Rare Diseases Research Consortium
Date: 16-17 April 2013
Venue: Dublin, Ireland

The IRDiRC Conference 2013 is organised by the European Commission during the Irish presidency of the European Union and aims to gather stakeholders active in the rare disease area from around the globe.
In addition to a top-level programme taking stock of advances towards the IRDiRC goals (“200 new therapies for rare diseases and means to diagnose most rare diseases by the year 2020”), the conference will provide ample opportunities to network with the international rare disease community. It will also feature a poster session to showcase projects contributing to IRDiRC objectives.

For further details

First Oxford Symposium on Rare Diseases: Protein Misfolding and Aggregation
Date: 31 Jan-1 Feb 2013
Venue: Oxford, UK

While the symposium has a scientific focus on rare misfolding diseases and small molecule therapy, the organisers aim to designate the all-inclusive event by bringing together academia, industry, clinicians, funders and patient groups. They strongly believe that having all communities and stakeholders together would be the best way to promote awareness for the unmet medical need, and build international collaborations and PPP in drug discovery for rare diseases.

For further details

Hereditary and Familial Cancer In The Personal Genomics Era
Date: 14-15 March 2013
Venue: Barcelona, Spain

The Institute of Predictive and Personalized Medicine of Cancer (IMPPC) and the Catalan Institute of Oncology (ICO) are providing a forum for professionals working with hereditary and familial cancers. The program combines the fields of Genomics for Public Health and Management of Hereditary Cancer and contains topics ranging from basic research to clinical applications.

For further details

World Cord Blood Congress IV and Innovative Therapies for Sickle Cell Disease
Date: 24-27 October 2013
Venue: Monaco

The World Cord Blood Congress will cover a wide range of topics including cord blood transplant in adults and children, the role of HLA in cord blood transplant, stem cells, cord blood banking and regulatory issues. An international panel of distinguished scientists and clinicians will participate in this forum over four days of interactive conferencing.

For further details

ESH International Conference on Multiple Myeloma
Date: 4-6 October 2013
Venue: Dublin, Ireland

The 2013 ESH International Conference on Multiple Myeloma will bring together a world-class faculty to offer a comprehensive overview of the most up-to-date treatment strategies for Multiple Myeloma.

For further details


Media, Press & Publications

A new journal on rare diseases

The first issue of the eponymous journal on rare diseases will be published in 2013. It is a peer-reviewed, open access, online journal and aims to publish “high-quality research addressing the underlying mechanisms of rare diseases”. Edited by Timur Yusufzai of the Harvard Medical School, Rare Diseases would include “studies of disease-related proteins, analyses of rare disease mutations, gene expression analyses of rare disease genes, genotype-phenotype correlations, studies of animal models, and novel clinical findings”. The journal is now accepting submissions.

Book traces revolutionary history of Duchenne muscular dystrophy (Meryon’s disease)

In their The History of a Genetic Disease: Duchenne muscular dystrophy or Meryon's disease, Alan Emery and Marcia Emery offer the reader an informative and insightful journey into the history of DMD – starting with its earliest cases, dating back to the eighteenth and the nineteenth century in the context of the molecular genetic revolution, the book follows with descriptions of major contributions since then, passing on to the review of advances in thinking in recent years in regard to the pathogenesis of muscular dystrophy. Each factual event is put into perspective with the description of the existing scientific climate of its time. The book also unfolds the stories of the two main contributors toward the description of the disease – Duchenne de Boulogne and Edward Meryon. A chapter devoted to Meryon’s contribution comes as a tribute to the physician, who “made an inspired and thoughtful study of the disease”.

Title: The History of a Genetic Disease: Duchenne muscular dystrophy or Meryon's disease
Author: Alan E.H. Emery, Marcia L.H. Emery
Publisher: Oxford University Press, 2012
ISBN: 978-0-19-959147-3

Second edition of Genetic Skin Disorders, by Virginia P. Sybert, is out

Genetic Skin Disorders provides accessible information on over 300 inherited dermatologic disorders. It comprises a section on differential diagnosis by skin signs and contains sections devoted to dermatologic features, associated clinical abnormalities, histopathology, biochemical and molecular information, treatment, mode of inheritance and recurrence risk and prenatal diagnosis. The new addition has information on treatment advances, new research advances and updated references.

Title: Genetic Skin Disorders
Author: Virginia P. Sybert
Publisher: Oxford University Press, 2012
ISBN: 978-0-19-539766-6


Orphanews Europe, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews Europe is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Contact Us
Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Helena Kaariainen, Odile Kremp, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Louise Taylor, Jaroslaw Waligora

EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Radka Tincheva (Bulgaria), Ivo Baric (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek Jr. (Czech Republic), Marianne Jespersen (Denmark), Inna Vabamae (Estonia), Helena Kaariainen (Finland), Alain Garcia (France), Birgit Schnieders (Germany), Christos Katamis (Greece), Janos Sandor (Hungary), Thor Thorarinsson (Iceland) , John Devlin (Ireland), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Romalda Baranauskiene (Lithuania) , Yolande Wagener (Luxembourg), Miriam Dalmas (Malta), Harry Seeverens (Netherlands), Stein Are Aksnes (Norway), Jacek Gralinski (Poland), Alexandre Diniz (Portugal), Ana Maria Vladareanu (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Isabel Pena-Rey (Spain), Andor Wagner (Sweden) , Sabina Gallati (Switzerland), Edmund Jessop (UK)
EUCERD ECDC Representative: Andrew Amato
EUCERD Patient Organisation Representatives: Dorica Dan, Yann Le Cam, Christel Nourissier, Bianca Pizzera
EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolène Aymé, Jean Donadieu, Dian Donnai, Laura Fregonese, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Sophie Koutouzov, Gerard Wagemaker
EUCERD European Commission Participants: Catherine Berens, Iiro Eerola, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Antoni Montserrat Moliner, Stefan Schreck, Bruno Sepodes (EMA-COMP), Jaroslaw Waligora

Orphanet Partner Country Representatives: Tamara F. Sarkisian (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), Manfred Stuhrmann-Spangenberg (Germany), Helen Michelakakis (Greece), András Becskeházi (Hungary), Andrew Green (Ireland), Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Viadutis 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)
For more information on the European Union Committee of Experts on Rare Diseases
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