10 June 2009 print
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The Rare Disease Task Force meeting report now available online

As was reported in the last issue of OrphaNews Europe, the Rare Disease Task Force met in Luxembourg on 30 April to discuss several topics. These included the status of the Council Recommendation on a European Action in the field of Rare Diseases, the Implementation Plan of the Council Recommendation and the Commission Communication, the Commission Decision setting up a European Union Advisory Committee on Rare Diseases, and the Call for Tenders and direct agreements in the framework of the Second Health Programme in 2009 (Newborn screening, Support to repertory activities, and Classification and Codification of rare diseases). A review of the outcomes of the European Rare Diseases Day in 2009, the state of the play of the Joint Action on support to the Rare Diseases Task Force and perspectives for the future were also discussed. Finally, a status report on the ongoing revision process of the World Health Organization International Classification of Diseases and an update on the EUROPLAN Project were presented. The full report of this meeting is now available on the RDTF website under the Meetings and Events section.

Spotlight on...
Agrenska ... twenty years of services for rare disease patients and families in Sweden

In the company of Her Majesty Queen Silvia of Sweden, celebrations were held in June to mark the twentieth anniversary of Agrenska, a non-profit organisation which has been providing unique services in Sweden to children and adults with disabilities since 1989. Rare disability and its impact on the family is the principal interest of the foundation, which bills itself as a national centre of competence for rare diseases and is organised and managed in part by disabled persons. The centre, which has Special Consultative Status with the Economic and Social Council of the United Nations, features a family programme, an adult programme, respite care, a consultant for attention deficit hyperactivity disorder, a family support unit, a learning programme for professionals, and personal assistance. The organisation offers expertise in paediatric and adult rare disabilities, and provides educational and vocation training. Agrenska works to build knowledge and skills amongst specific target groups. Chaired by Anders Olauson, (former president of the European Organisation for Rare Diseases (EURORDIS) and current president of the European Patients’ Forum), the Agrenska centre offers programmes and services for children and adult rare disease patients, as well as for families, and for health professionals involved with patients. The family programme includes all members of the family and provides a venue for those families coping with the same rare disease to come together. The week-long programmes focus on one disease at a time and invite the professionals working with the participating children to attend for two days of interchange. International experts are also often invited. There are informational sessions for parents as well as a programme geared to the siblings of patients. For the children and their siblings, a balanced schedule of educational and leisure activities is devised. These family programmes occasionally serve as the backdrop for an international conference on a specific disease or set of diseases.

Weekend respite care and summer camp
Amongst the services available at the Agrenska centre are the respite service and summer camp programmes. The respite care programmes are offered weekends and during school holidays and are available to children and adolescents with a variety of impairments - physical, cognitive and behavioural. Attendees are organised into groups as homogeneous as possible and gather regularly once a month, thus allowing the opportunity to encounter the same participants and staff team each time. Each group has a set of goals that contribute to enhancing independence and self-determination. The programmes allow participants to work on social skills and friendship development while learning more about their disability. The summer camps are week-long events and include participants from the weekend groups. Some participants stay for two weeks. There are also day camps for younger children. These programmes permit the families to have some time away from the daily responsibilities of caring for a member with a rare disease.

The adult programme
In 2005 Agrenska branched out with its Adult programme. This unique model, held in tandem with the country’s national association for rare diseases, Riksforbundet Sallsynta Diagnoser, and financed in part by the Swedish inheritance fund, brings together patients with the same disorder for four-day informative workshops. Patients learn about and discuss the medical, social, educational, and psychological elements of their condition. There are six different workshops held per year. The overall aim of these workshops is to enhance the coping skills of rare disease patients by arming them with tools and knowledge. Information from these events is gathered and published online for the benefit of other patients with the same disorder as well as for the professionals working with patients. Workshops have been held for Ehlers-Danlos syndrome, Marfan syndrome, Turner syndrome, neurofibromatosis, PKU, Noonan syndrome, CATCH 22, Prader-Willi syndrome, congenital limb deficiency, Klinefelter syndrome, Gaucher disease, and arthrogryposis multiplex congenita. Participants report feeling empowered and better prepared to handle their everyday lives following these programmes.

The Estonian Agrenska Foundation
Located in Tartu county, the Estonian Agrenska Foundation was founded by several sources including Agrenska Sweden, the University of Tartu, the Estonian Board of Disabled People, the Tartu University Hospital Foundation, and Stenstroms Skjortfabrik Eesti, a shirt manurfacturer. Like its Swedish counterpart, the Estonian Agrenska Foundation targets the family, offering a family-centred counselling system that covers all of Estonia and focuses on families of children with disabilities, offering psychosocial, educational and medical information and support. The centre is housed in the Tammistu manor, which was generously donated by the Stenstrom family. Anders Olauson also serves as chairman for this centre.

A published study conducted by researchers from the department of economics at the University of Gothenburg determined that the Agrenska approach to rare disease care is cost effective. The study, appearing in the review PharmacoEconomics, found a "three-fold decrease in direct and indirect healthcare costs" for those families participating in Agrenska Centre programmes versus those that use only traditional routine support services. Spain, Argentina and Australia are currently developing centres based on the Agrenska model and several other countries are in discussions. Agrenska’s role in the United Nations reflects its understanding of the common issues all rare disease patients and their families share.

No matter which country they are from," observed Anders Olauson in a recent interview with OrphaNews Europe, "For a family with a child with a rare disorder, the impact from a holistic perspective is essentially the same.
For further information on Agrenska


National & International Policy Developments
The second French National Plan for Rare Diseases in preparation

The Committee responsible for following up the first French National Plan for Rare Diseases (2005–2008) met on 28 May to draw conclusions from the evaluation reports and launch the elaboration process for the next version of the plan. The evaluation of the actions of the first plan was qualified as very positive but justifies a second phase of the plan in order to complete what has not yet been accomplished. Efforts should concentrate on improving the coding of rare diseases in national health information systems in order to obtain the tools needed to monitor the impact of the plan and supporting registries and databases. The training of health professionals is still considered insufficient and should benefit from new initiatives which have yet to be defined. The situation of the centres of reference, which has very much improved over the past five years, should be scrutinised to avoid perverse effects such as the withdrawal of other resources to compensate the current additional funding earmarked for rare disorders - a threat judged to be significant by many. A better connection with the sector of French administration for Disability is also a major objective of the new plan, which should be drafted in July and August to be presented in September.

In order to improve the coordination of all actions, an inter-ministerial delegate is expected to be nominated soon. This person will immediately set up a drafting group for each of the six axes of the new plan which have been agreed to. Each of these six strategic axes will target specific issues: The first axe, “Development Indicators” will work for the development of diverse complex tools providing the necessary knowledge to better monitor the impact of the various actions of the plan. Axe two “Health Care Coverage” will seek to better coordinate medicinal and related services usage and ensure equity. The third axe, “Information and Training” will reinforce support to Orphanet, improve information on disability by coordinating with appropriate national counterparts, and ameliorate rare disease training in France. The fourth axe “Organisation of Care and Diagnostics” will pursue support for diagnostics and will tweak the actions taken vis-a-vis the centres of reference in order to meet any needs not currently covered in this area. Resources will be structured to implicate extra-hospital services as well as the country’s rare disability schema under preparation. The fifth axe “European and International Cooperation” will seek enhanced collaboration with industrialised and developing countries in the areas of information, public/private partnerships, research, epidemiology, networks of expertise, et cetera. Finally, the sixth axe, “Research and Development” will seek an evolution of the Institute for Rare Diseases, France’s main clearinghouse for calls for proposals in the field of rare disease research. Research will continue on the epidemiology and natural history of rare diseases, genetics, physiopathological mechanisms and therapeutics. It is important to remember that these elements identified for priority in the second plan build upon the groundwork of achievements accomplished in these and other areas during the first four years of the French plan.

Other European news
Off-label medication usage in Switzerland
"Off-label" refers to the practice of prescribing an authorised medicinal product that has been tested for safety and efficacy for use outside the scope of the approved indication. Many rare diseases with no specific treatment of their own are treated via off-label prescription. Indeed, off-label prescription may provide the only therapeutic or preventive strategy available. In a French-language article, the authors describe the practice of off-label medication use as it is observed in Switzerland. Off-label usage is estimated at 21% for ambulatory and 25% for hospital-based adult patients. Off-label use in 2007 was estimated at 50%-60% for paediatric patients while 90% of neonatal intensive care prescriptions were off-label. These statistics reflect the lack of studies undertaken in paediatric populations, a situation that is improving with the introduction of the Paediatric Regulation in January 2007 governing the development and authorisation of medicines for use in children. In Swiss professional reference materials (such as the Swiss compendium of medicines) three-fourths of the medicines described lack data for paediatric patients. For rare disease patients, off-label prescription is practiced because there is often no other therapeutic strategy available for these patients. However, such usage may not be subject to reimbursement by the state insurance system. Indeed, the authors note a trend of tightening purse strings when it comes to reimbursing non-approved medicinal product use. Swissmedic, Switzerland’s national regulatory agency for medicinal products, gives precise recommendations for responsible off-label use. The prescribing physician must be able to demonstrate diligent consideration of the known scientific properties of a product concerning safety when issuing an off-label prescription. Furthermore, furnishing full and complete information to patients is crucial, notably possible increased risks of side effects stemming from off-label use. Patients must also be informed that the product may not be eligible for reimbursement. In Switzerland, as in many countries, the prescribing physician is ultimately responsible for the decision to prescribe an off-label medicinal product and also for any possible side effects that result. The article concludes with a set of recommendations to enhance the safety of the practice of off-label medicine use.
Read the PubMed abstract (in English)

Other International News
24 million dollar NIH rare disease drug development pipeline launches to support preclinical research
In the USA, the National Institutes of Health (NIH) has announced an innovative programme that takes existing processes for drug development in the pharmaceutical industry as its framework, seeking to improve upon these processes and capitalise on cooperation with academic researchers working on rare and neglected conditions. The Therapeutics for Rare and Neglected Diseases programme (TRND) is being billed as a "trans-NIH initiative" that creates a drug development pipeline within the NIH. TRND will collaborate with "disease-specific experts" to undertake a large part of the preclinical stages of research. Some 80%-90% of preclinical research never makes it to the clinical phase. TRND, following the general preclinical model used by biopharmaceutical companies, will be applied to rare and neglected diseases that are often overlooked by private industry for financial reasons. Preclinical research is a timely and expensive process and in a press release, NIH Acting Director Raynard S. Kington observed that the "federal government may be the only institution that can take the financial risks needed to jumpstart the development of treatments for these diseases, and NIH clearly has the scientific capability to do the work." Office of Rare Disease Research Director Stephen C. Groft added that "...this is the first time NIH is providing support for specific, preclinical research and product development known to be major barriers preventing potential therapies from entering into clinical trials for rare or neglected disorders". National Human Genome Research Institute (NHGRI) Acting Director Alan E. Guttmacher explained that "TRND will develop promising treatments for rare diseases to the point that they are sufficiently "de-risked" for pharmaceutical companies, disease-oriented foundations, or others, to undertake the necessary clinical trials".

The $US24 million (€17.1 million) budget for fiscal year 2009 will build upon the successes of the similarly structured NIH Chemical Genomics Center (NCGC), which has a high-throughput screening system and over 350,000 compounds at its disposal. NCGC Director and Senior Advisor for Translational Research to the NHGRI Director, Christopher P. Austin, explained that the funding will allow for the establishment of "teams of scientists who can do the hard work of optimizing chemicals that we or others discover that may treat rare diseases and turn them into actual drugs." He elaborated that in contrast to traditional medicinal product development that only publishes successful endeavours, "we will publish our failures as well, so everyone in the drug development community can learn from them. That alone could be revolutionary."

TRND will collaborate with many external partners to overcome obstacles inherent in rare disease drug research, such as a lack of knowledge of the cause and natural history of a given disease coupled with difficulties identifying and recruiting adequate numbers of patients for clinical trials. Thus the programme hopes to work with patient organisations and academic researchers. For preclinical successes, the initiative will capitalise on other NIH resources to help facilitate human studies. These include the NIH Clinical Center, the NIH Rapid Access to Interventional Development (NIH-RAID), and the Clinical and Translational Science Awards (CTSA) programme. TRND will also address the process of clinical drug development - devising approaches that accelerate the process while lowering expenses. The initiative is constructing a process to determine which of the thousands of rare and neglected disorders to include. A certain number of conditions will be studied annually, "with strict criteria used to determine which molecules will be studied for which diseases". Licensing for any medicinal products discovered through the programme could be transferred to private biopharmaceutical companies for further development and marketing.
Consult the FAQ on the Therapeutics for Rare or Neglected Diseases (TRND) program

Database tool helps DECIPHER rare chromosomal disorders
An article in the American Journal of Human Genetics provides an update on a useful interactive web-based tool that aids in the interpretation of sub-microscopic chromosomic microdeletions/duplications/insertions, translocations and inversions and displays this information on the human genome map. DECIPHER, the DatabasE of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources, seeks to increase medical and scientific knowledge of chromosomal rearrangements in order to improve both medical care and genetic advice for individuals and families with submicroscopic chromosomal imbalances and to facilitate research into the study of genes that impact human development and health. Because many chromosomic aberrations are novel or extremely rare, clinical interpretation can be problematic and genotype-phenotype correlations are uncertain. By cataloguing common copy-number changes in normal populations, changes that are novel and potentially pathogenic can be identified by exclusion. With DECIPHER, "known and predicted genes within an aberration are listed in the patient report, and genes of recognised clinical importance are highlighted and prioritised. DECIPHER enables clinical scientists worldwide to maintain records of phenotype and chromosome rearrangement for their patients and, with informed consent, share this information with the wider clinical research community through display in the genome browser Ensembl. By sharing cases worldwide, clusters of rare cases having phenotype and structural rearrangement in common can be identified, leading to the delineation of new syndromes and furthering understanding of gene function".
Read the PubMed abstract of the American Journal of Human Genetics article

Talk about a revolution...the Concept Web Alliance seeks to rocket life-science data exploitation to a new dimension
With an estimated six million pages per year being added to the 100 million-plus page-equivalent store of life-science data currently available, methodologies are needed to "make massive data interoperable, non-ambiguous, non-redundant and accessible". To address the challenges related to this ever-increasing amount of life-science data, an international non-profit organisation, the Concept Web Alliance (CWA), has been formed in order to exploit emerging web applications to better harness information. CWA provides a collaborative environment for academics from different disciplines to address the volume and the complexity of current scientific data and communication. The initial European focal point of CWA is hosted in the Netherlands Bioinformatics Centre. In the USA, the focal point is located at the Stanford University Center for Biomedical Informatics Research. The initiating group has members from six different global locations.

Starting from a rationale that "traditional formats to capture complex information are no longer adequate to absorb, analyze and share the current scientific output," CWA is looking to new models, such as semantically rich triple content from the Resource Description Framework (a family of World Wide Web Consortium specifications) that could engender improved methodologies for knowledge discovery. In triples (subject-predicate-object expression data models) the subject denotes the resource, while the predicate designates specific traits and/or aspects of the resource and expresses a relationship between the subject and the object. Such a mechanism for describing resources is a component of the next evolutionary stage of the World Wide Web - the Semantic Web - which will allow automated software to stock, share and exploit web-based information, permitting web users to access and treat information more efficiently. CWA asserts that triples represent "concept-relation-concept facts of curated, observational and hypothetical connections [that] form a dynamic Concept Web". CWA technology has so far mined PubMed and is using Wiki technology for collaborative annotation of life-science concepts. The WikiProfessional interface presents the results of these featuresets (PubMed searching & filtering at the concept level along with results from the WikiProfessional records). In early May, the CWA held its inaugural meeting in New York. During the event, a Declaration was unveiled and signed by participants, establishing the mission of CWA as follows:

"To enable an open collaborative environment to jointly address the challenges associated with high volume scholarly and professional data production, storage, interoperability and analyses for knowledge discovery".

The Declaration iterates the need for international collaboration - especially when sources such as high throughput gene expression and sequencing data, and biobanks, are included in the concept-relation-concept triples capture. During the inaugural meeting, founders of CWA defined the alliance as a forum uniting key stakeholders, a facilitator promoting various triple content services, and as a repository - serving as a distributor and agent for both contributors and users of triples. Participants from academic, informatics, scientific and medical institutions, publishing houses, and organisations offered their signatures in support for the declaration, including participants from the Netherlands Bioinformatics Centre, Thomson Reuters, the French National Institute for Scientific and Technical Information, Karolinska Institute, PLoS, Nature Genetics - and Orphanet. Indeed, the possibilities offered by the CWA could prove crucial to optimising rare disease information access and interoperability. The field of rare diseases could be one of the life science disciplines that stands to gain the most from this revolution in accessing data electronically.
Related reading


Orphanet News
Orphanet featured in the international media
International news leader CNN recently gave a plug to Orphanet in a special news series on rare diseases. The CNN feature ran a number of articles on rare diseases, including a Rare Diseases Resource Guide that lists Orphanet and includes a link to the homepage. Other articles in the series include a quiz on rare diseases and a special feature on very rare disorders.
View the CNN rare disease feature article

New Texts
Angelman syndrome (published in the European Journal of Human Genetics, in association with Orphanet)

New Syndromes
A novel microdeletion syndrome with microcephaly, developmental delay, dysmorphic features and hearing loss
Interstitial deletions of 6q are rare. The authors report a detailed clinical and molecular characterisation of four patients with interstitial deletion involving 6q25 who presented with microcephaly, developmental delay, dysmorphic features and hearing loss. Two patients also had agenesis of the corpus callosum. The authors determined the size, extent and genomic content of the deletions, determining that a common segment spanning 3.52 Mb within the 6q25.2-q25.3 region was deleted in all four cases.
Read the PubMed abstract

Eur J Hum Genet ; 573-581 ; May 2009
Wernicke-like encephalopathy with mutations in a thiamine-transporter gene
The authors describe two brothers with a recessive syndrome clinically identical to Wernicke encephalopathy but with no thiamine deficit. The two brothers have epilepsy, nystagmus, ophthalmoplegia, and ataxia. Genetic analysis identified two mutations in the gene SLC19A3, encoding a thiamine transporter.
Read the PubMed abstract

N Engl J Med ; 1792-1794 ; 23 April 2009

New Genes

Nonsyndromic optic atrophy: TMEM126A, encoding a mitochondrial protein, is mutated
Nonsyndromic autosomal-recessive optic neuropathies are rare conditions of unknown genetic and molecular origin. The authors have identified the first gene responsible for this condition, TMEM126A, in a large multiplex inbred Algerian family and subsequently in three other families originating from the Maghreb. TMEM126A is conserved in higher eukaryotes and encodes a transmembrane mitochondrial protein of unknown function, supporting the view that mitochondrial dysfunction may be a hallmark of inherited optic neuropathies including isolated autosomal-recessive forms.
Read the PubMed abstract

To read more about "Optic atrophy"

Am J Hum Genet ; 493-498 ; April 2009
Human male infertility caused by mutations in the CATSPER1 channel protein
Male infertility, a common barrier that prevents successful conception, is a reproductive difficulty affecting 15% of couples. Genetic forms of nonsyndromic male infertility can arise from single-gene defects as well as chromosomal abnormalities. Although no CATSPER gene has been identified as causative for human male infertility, male mice deficient for members of the CatSper gene family are infertile. In this study, the authors describe three men from two consanguineous families presenting sterility characterised by a low spermazoid count, weak motility and morphological anomalies. Genetic analysis identified mutations in CATSPER1, one of four members of the sperm-specific CATSPER voltage-gated calcium channel family known to be essential for normal male fertility in mice.
Read the PubMed abstract

Am J Hum Genet ; 505-510 ; April 2009
Hypomagnesemia: a missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked
Primary hypomagnesemia is a heterogeneous group of disorders characterised by renal or intestinal magnesium (Mg2+) wasting, resulting in tetany, cardiac arrhythmias, and seizures. The kidney plays an essential role in maintaining blood Mg2+ levels, with a prominent function for the Mg2+-transporting channel transient receptor potential cation channel, subfamily M, member 6 (TRPM6) in the distal convoluted tubule (DCT). In the DCT, Mg2+ reabsorption is an active transport process primarily driven by the negative potential across the luminal membrane. Here, the authors studied a family with isolated autosomal dominant hypomagnesemia and identified a mutation in KCNA1, a gene encoding the voltage-gated potassium (K+) channel Kv1.1. Kv1.1 was found to be expressed in the kidney, where it colocalized with TRPM6 along the luminal membrane of the DCT. Upon overexpression in a human kidney cell line, the KCNA1 mutation resulted in a nonfunctional channel, with a dominant negative effect on wild-type Kv1.1 channel function.
Read the PubMed abstract

J Clin Invest ; 936-942 ; April 2009
Retinitis pigmentosa: the role of isocitrate dehydrogenases in the Krebs cycle
The authors describe two families with retinitis pigmentosa, a hereditary neurodegeneration of rod and cone photoreceptors in the retina. Affected family members were homozygous for loss-of-function mutations in IDH3B, encoding the beta-subunit of NAD-specific isocitrate dehydrogenase. Loss of function of this enzyme, implicated in the Krebs cycle, had no other clinical consequences aside from retinitis pigmentosa.
Read the PubMed abstract

To read more about "Retinitis pigmentosa"

Nat Genet ; 1230-1234 ; October 2008
Familial ischemic cerebral small-vessel disease: HTRA1 mutations implicated
The genetic cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which is characterised by ischemic, nonhypertensive, cerebral small-vessel disease with associated alopecia and spondylosis, is unclear. In five families with CARASIL, the authors identified two nonsense mutations and two missense mutations in HTRA1, encoding a serine protease that represses signaling by TGF-beta family members. These findings indicate a link between repressed inhibition of signalling by the TGF-beta family and ischemic cerebral small-vessel disease, alopecia, and spondylosis.
Read the PubMed abstract

N Engl J Med ; 1729-1739 ; 23 April 2009
UV-sensitive syndrome: a specific CSA mutation reveals separable roles in response to UV and oxidative DNA damage
UV-sensitive syndrome (UV-SS) is a recently-identified autosomal recessive disorder characterised by mild cutaneous symptoms and defective transcription-coupled repair (TC-NER). Cockayne syndrome (CS) is another genetic disorder with sun sensitivity and defective TC-NER, caused by mutations in the CSA or CSB genes. The authors report the identification of a UV-SS patient with a novel mutation in the CSA gene that confers hypersensitivity to UV light, but not to inducers of oxidative damage that are notably cytotoxic in cells from CS patients.
Read the PubMed abstract

To read more about "UV-sensitive syndrome"

Proc Natl Acad Sci USA ; 6209-6214 ; 14 April 2009
X-linked myopathy with excessive autophagy: VMA21 deficiency compromises V-ATPase activity and lysosomal acidification
X-linked myopathy with excessive autophagy (XMEA) is a childhood-onset disease characterised by progressive vacuolation and atrophy of skeletal muscle. The authors show that XMEA is caused by hypomorphic alleles of the VMA21 gene, encoding an essential assembly chaperone of the V-ATPase, the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH, which reduces lysosomal degradative ability and blocks autophagy. This reduces cellular free amino acids, which upregulates the mTOR pathway and mTOR-dependent macroautophagy, resulting in proliferation of large and ineffective autolysosomes that engulf sections of cytoplasm, merge together and vacuolate the cell.
Read the PubMed abstract

To read more about "X-linked myopathy with excessive autophagy"

Cell ; 235-246 ; 17 April 2009

Research in Action

Fundamental Research
Xeroderma pigmentosum: a rare disease furnishes molecular evidence of the role of UV in melanomas
To look for a direct role of ultraviolet radiation (UV) exposure in cutaneous melanoma induction, the authors studied xeroderma pigmentosum (XP) patients who have defective DNA repair resulting in a 1000-fold increase in melanoma risk. XP melanomas have the same anatomic distribution as melanomas in the general population. Samples from 59 melanomas (47 melanomas in situ and 12 invasive melanomas) from 8 XP patients showed mutations in the PTEN tumour suppressor gene in 56% of the melanomas. 91% of the melanomas with mutations had 1 to 4 UV type base substitution mutations. UV damage plays a direct role in induction of mutations and in inactivation of the PTEN gene in XP melanomas including in situ, the earliest stage of melanoma. These data provide solid mechanistic support for UV protection for prevention of melanoma.
Read the PubMed abstract

To read more about "Xeroderma pigmentosum"

Proc Natl Acad Sci USA ; 6279-6284 ; 14 April 2009
Clinical Research
13q deletions: an update of the phenotypic map of 13q21.1-qter
Partial deletions of the long arm of chromosome 13 lead to variable phenotypes dependant on the size and position of the deleted region. The authors refined the smallest deletion region linked to short stature, microcephaly, cortical development malformations, Dandy-Walker malformation, corpus callosum agenesis, meningocele/encephalocele, DWM, CCA, and neural tube defects taken together, ano-/microphthalmia, cleft lip/palate, lung hypoplasia, and thumb a-/hypoplasia. Most of the individuals with deletion of any part of 13q21qter showed surprisingly similar facial dysmorphic features, and thus, a "13q deletion facial appearance" was suggested.
Read the PubMed abstract

To read more about "Distal monosomy 13q"

Am J Med Genet ; 894-905 ; May 2009
Klinefelter syndrome: psychiatric characteristics in a sample of boys
Klinefelter syndrome has been widely associated with cognitive impairment and language problems. To explore the extent of psychiatric morbidity in children and adolescents with Klinefelter syndrome, 51 subjects aged 6 to 19 years were screened by using structured and standardised assessment procedures covering the full range of psychiatric problems and disorders. A wide range of anomalies could be observed, with language disorder (65%) as the most prevalent disorder, followed by attention-deficit disorders (63%) and autism spectrum disorder (27%). Behavioural impairment was most evident among cases classified as autism spectrum disorder and psychotic disorder (12%).
Read the PubMed abstract

To read more about "Klinefelter syndrome"

Pediatrics ; e865-870 ; May 2009
CHARGE syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features
CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome have significant clinical overlap including cardiac anomalies, ear abnormalities, hearing loss, developmental delay, renal abnormalities, and cleft palate. Immunodeficiency has been well documented in 22q11.2 deletion, but there has been limited recognition of this potentially serious complication in CHARGE syndrome. The authors studied 25 children diagnosed with CHARGE syndrome with positive CHD7 mutations. Findings were compared to data available for a large cohort of patients with 22q11.2 deletion syndrome. The presence of coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, or genital hypoplasia in boys should alert the clinician to the possibility of CHARGE syndrome rather than the 22q11.2 deletion. Molecular testing for CHD7 mutations may help to confirm the diagnosis. In this study, significant hypocalcemia and lymphopenia occurred more frequently in patients with CHARGE syndrome than in those with 22q11.2 deletion syndrome. Early inclusion of immunologists to the multidisciplinary care team (as with 22q11.2 deletion) may be of great benefit to affected patients.
Read the PubMed abstract

To read more about "Monosomy 22q11"

Pediatrics ; e871-877 ; May 2009
Silver-Russell syndrome: normal intrauterine growth does not exclude syndrome
Silver-Russell syndrome is a heterogenous disorder characterised by severe intrauterine growth restriction, lack of catch-up after birth, and specific dysmorphisms. The authors report on molecular testing in 188 patients referred for routine diagnostics of Silver-Russell syndrome and in a group of 20 patients with isolated intrauterine growth restriction/postnatal growth retardation. In addition to patients with the classical Silver-Russell syndrome phenotype fulfilling the Silver-Russell syndrome-specific scores, genetic testing for 11p15 epimutation and/or maternal uniparental disomy of chromosome 7 should also be considered in case of "Silver-Russell syndrome-like" phenotypes; for example, mild intrauterine growth restriction and postnatal growth retardation associated with a prominent forehead and triangular face or asymmetry as the only clinical signs. The lack of intrauterine growth restriction in patients with a Silver-Russell syndrome-like phenotype should not automatically result in exclusion from molecular testing.
Read the PubMed abstract

To read more about "Silver-Russell syndrome"

Pediatrics ; e929-931 ; May 2009
Cystic fibrosis: identification of IFRD1 as a modifier gene
In cystic fibrosis, chronic infection and dysregulated neutrophilic inflammation lead to progressive airway destruction. The severity of cystic fibrosis lung disease has considerable heritability, independent of CFTR genotype. The authors identified IFRD1 as a modifier of cystic fibrosis lung disease severity. IFRD1 is a histone-deacetylase-dependent transcriptional co-regulator expressed during terminal neutrophil differentiation. IFRD1 deficiency caused delayed bacterial clearance from the airway. IFRD1 polymorphisms were significantly associated with variation in neutrophil effector function.
Read the PubMed abstract

To read more about "Cystic fibrosis"

Nature ; 1039-1042 ; 23 April 2009
Prader-Willi syndrome: paternal deletions of MKRN3, MAGEL2 and NDN not at cause in two patients
Prader-Willi syndrome (PWS), a rare genetic disorder characterised by hypothalamic-pituitary abnormalities with severe hypotonia, the onset of hyperphagia with a risk of morbid obesity, learning difficulties, behavioural problems and/or severe psychiatric problems, is caused by a 5-6 Mbp de novo deletion on the paternal chromosome 15, maternal uniparental disomy 15 or an imprinting defect. All three lesions lead to the lack of expression of imprinted genes that are active on the paternal chromosome only. The contribution to PWS of any of these genes is unknown, because no single gene mutation has been described so far. The authors report on two patients with PWS who have an atypical deletion on the paternal chromosome that does not include MKRN3, MAGEL2 or NDN.
Read the PubMed abstract

To read more about "Prader-Willi syndrome"

Eur J Hum Genet ; 582-590 ; May 2009
Nodulosis-arthropathy-osteolysis syndrome: congenital heart defects in a Turkish family with the disease
Multicentric osteolysis with nodulosis and arthropathy is an autosomal recessive member of the "vanishing bone" syndromes and is notable for the extent of carpal and tarsal osteolysis and interphalangeal joint erosions, facial dysmorphia, and the presence of fibrocollagenous nodules. This rare disorder has been described previously in Saudi Arabian and Indian families. The authors now report on the first Turkish family with this disease. In addition to the previously noted skeletal and joint features, affected members of this family also had congenital heart defects. Molecular analysis identified a novel MMP2 inactivating mutation that confirmed the diagnosis.
Read the PubMed abstract

To read more about "Nodulosis-arthropathy-osteolysis syndrome"

Eur J Hum Genet ; 565-572 ; May 2009
Alpha 1 antitrypsin deficiency in Tunisian subjects with obstructive lung disease: a screening feasibility report
Alpha 1 antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterised by low serum levels of AAT, the main protease inhibitor (PI) in human serum. It is generally accepted that AATD in North African populations is not a risk factor for lung and/or liver disease, based on a number of small studies. The authors conducted a screening study for detection of AATD in 120 patients with obstructive lung disease (OLD) in Tunisia. They found 6 OLD patients carried AAT deficient alleles. Thus alleles related to AATD are not absent in the Tunisian population. These results support a larger scale screening for AATD in Tunisia.
Read the PubMed abstract

To read more about "Alpha-1 antitrypsin deficiency"

Orphanet J Rare Dis. 2009 Apr 15 ; 4:12 ; 15 April 2009
SLE: new insights from fine mapping and genome-wide association studies
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and characterised by the presence of autoantibodies directed against nuclear antigens. Genome-wide association studies and fine mapping of candidate regions have rapidly advanced understanding of the genetic basis of SLE. More than 20 robust associations have now been identified and confirmed, providing insights at the molecular level that refine understanding of the involvement of host immune response processes. In addition, genes with unknown roles in SLE pathophysiology have been identified. These findings may provide new routes towards improved clinical management of this complex disease.
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To read more about "Lupus erythematosus, systemic"

Nat Rev Genet ; 285-290 ; May 2009
Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity
Acquired myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction in which patients experience fluctuating skeletal muscle weakness that often affects selected muscle groups preferentially. Accumulating evidence suggests that clinical MG subgroups might respond differently to treatment. In this article, the authors provide current information about the epidemiology, immunopathogenesis, clinical presentations, diagnosis, and treatment of MG, including emerging therapeutic strategies.
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To read more about "Myasthenia gravis"

Lancet Neurol ; 475-490 ; May 2009
Therapeutic Approaches
Hemophilia: successful treatment of canine hemophilia by continuous expression of canine FVIIa
Hemophilia is a genetic disorder determined by an abnormal gene on the X chromosome. Continuous expression of activated factor VII (FVIIa) via gene transfer is a potential therapeutic approach for patients with or without inhibitory antibodies to human factor VIII (FVIII) or IX (FIX). The authors investigated whether gene transfer of an engineered canine FVIIa (cFVIIa) transgene can affect hemostasis in a canine model of hemophilia, a good predictor of efficacy of hemophilia treatments. Their study provides the first evidence for in vivo efficacy and safety of continuously expressed FVIIa as a FVIII/FIX-bypassing agent in a large animal model of hemophilia, avoiding the risk of inhibitor formation associated with bolus FVIII or FIX infusion.
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To read more about "Hemophilia"

Blood ; 3682-3689 ; 16 April 2009
Duchenne muscular dystrophy: valproic acid improves pathology in a mouse model
Duchenne muscular dystrophy is a lethal neuromuscular disease that currently has no effective therapy. Transgenic overexpression of the alpha7 integrin in mdx/utrn(-/-) mice, a model of Duchenne muscular dystrophy, ameliorates the disease. To evaluate the potential use of Valproic acid (VPA) to treat muscular dystrophy, mdx/utrn(-/-) mice were injected with the drug. Treatment with VPA lowered collagen content and fibrosis, and decreased hind limb contractures. VPA-treated mice also had increased sarcolemmal integrity and decreased damage, decreased CD8-positive inflammatory cells, and higher levels of activated Akt in their muscles. Thus, VPA has important biological effects that may be applicable for the treatment of muscular dystrophy.
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To read more about "Duchenne and Becker muscular dystrophy"

Am J Pathol ; 999-1008 ; March 2009
Diagnostic Approaches
Limb-girdle muscular dystrophy 2A: a multistep diagnostic approach
Limb-girdle muscular dystrophy (LGMD) 2A (calpainopathy) is the most frequent form of LGMD in many European countries. The increasing demand for a molecular diagnosis makes the identification of strategies to improve gene mutation detection crucial. The authors describe a multistep diagnostic approach that has improved the detection rate of the disease. An extension of screening to presymptomatic phenotypes has allowed early diagnoses, which has important consequences for patient care and genetic counselling.
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To read more about "Muscular dystrophy, limb-girdle, autosomal recessive, type 2A"

Eur J Hum Genet ; 598-603 ; May 2009

Patient Management and Therapy

Severe combined immunodeficiency: positive long-term outcome after hematopoietic stem cell transplantation
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for severe combined immunodeficiency (SCID). The authors performed a single-centre retrospective analysis of the long-term outcome of HSCT in a 90-patient cohort followed between 2 and 34 years (median, 14 years). Clinical events and immune reconstitution data were collected. Almost half the patients have experienced one or more significant clinical event, including persistent chronic graft-versus-host disease (GVHD), autoimmune and inflammatory manifestations, opportunistic and non-opportunistic infections, chronic human papilloma virus (HPV) infections, and a requirement for nutritional support. With the notable exception of severe HPV infection, these complications tend to become less common 15 years later after HSCT. In most cases, HSCT enables long-term survival with infrequent sequelae. However, the occurrence of relatively late-onset complications is a concern that requires specific means of prevention and justifies careful patient follow-up.
Read the PubMed abstract

Blood ; 4114-4124 ; 23 April 2009
Hemophilia: inhibitors of factor VIII in black patients
Black patients with hemophilia A (factor VIII deficiency) are twice as likely as white patients to produce inhibitors against factor VIII proteins given as replacement therapy. There are six wild-type factor VIII proteins, designated H1 through H6, but only two (H1 and H2) match the recombinant factor VIII products used clinically. H1 and H2 are found in all racial groups and are the only factor VIII proteins found in the white population to date. H3, H4, and H5 have been found only in blacks. In this study, the authors demonstrate that mismatched factor VIII transfusions may contribute to the high incidence of inhibitors among black patients.
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To read more about "Hemophilia"

N Engl J Med ; 1618-1627 ; 16 April 2009
Targeted population carrier screening effective for severe and frequent genetic diseases in Israel
A national carrier screening program targeted at communities in which severe genetic diseases are present with a frequency higher than 1/1000 live births has been in existence in Israel since 2002. During the first 5 years of the programme more than 13 000 tests were performed, and at the end of 2007 screening was offered in 35 different localities/communities for a total of 36 diseases. Many of the couples identified to be at risk opted for prenatal diagnosis and in two cases an affected pregnancy was terminated. In some cases the couples declined prenatal diagnosis and two of those families gave birth to an affected child. Based on the experience learnt from this targeted screening program it appears that a knowledge-based, voluntary screening program operated within the community is an effective way to provide genetic services and test referrals.
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Eur J Hum Genet ; 591-597 ; May 2009
Waldenstrom macroglobulinemia: long-term outcomes of fludarabine and rituximab
Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterised by the accumulation of monoclonal cells in the bone marrow and peripheral lymphoid tissues, and associated with the production of an IgM serum monoclonal protein. The authors report the long-term outcome of a multicentre, prospective study examining fludarabine and rituximab in 43 WM patients with less than 2 prior therapies. The results of this study demonstrate that fludarabine and rituximab are highly active in WM, although short- and long-term toxicities need to be carefully weighed against other available treatment options.
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To read more about "Waldenström macroglobulinemia"

Blood ; 3673-3678 ; 16 April 2009

Orphan Drugs
Two orphan products receive recommendations for marketing authorisation at May CHMP meeting
At the May 2009 meeting of the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP), a positive opinion was adopted recommending marketing authorisation for Afinitor (everolimus) from Novartis Europharm Ltd. for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with vascular endothelial growth factor-targeted therapy. Afinitor is the 55th orphan medicine to receive a positive opinion from the CHMP.

Mozobil (plerixafor), intended for use in combination with granulocyte-colony stimulating factor to enhance the mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with lymphoma and multiple myeloma whose cells mobilise poorly, became the 56th orphan medicine to receive a positive opinion from the CHMP. Mozobil is produced by Genzyme Europe B.V.

Finally, after re-examination of a negative opinion adopted in January 2009, a final positive opinion under exceptional circumstances, subject to certain specific obligations to be reviewed annually, was adopted for Vedrop (tocofersolan), intended for the treatment of vitamin E deficiency due to digestive malabsorption in paediatric patients suffering from congenital chronic cholestasis or hereditary chronic cholestasis. Chronic cholestasis is present in several rare conditions. Vedrop is produced by Orphan Europe S.A.R.L.

FDA approves a treatment for glioblastoma multiforme and a pancreatic enzyme replacement product
In the United States, the Food and Drug Administration (FDA) has approved extending the indication of Avastin (bevacizumab) to treat patients with glioblastoma multiforme (GBM) when the disease continues to progress following standard therapy. Avastin is manufactured by Genentech Inc.

The FDA also approved pancreatic enzyme replacement product Creon (pancrelipase) for patients with cystic fibrosis and others with exocrine pancreatic insufficiency. Creon aids patients to digest and absorb nutrients from foods and is the first FDA-approved delayed-release pancreatic enzyme replacement product to be marketed in the United States as a result of the FDA unapproved drugs initiative. Creon, from Solvay Pharmaceuticals, is approved for use in paediatric and adult patients.


PhD studentship for Living with Duchenne Muscular Dystrophy study
Applications are invited for an ESRC Collaborative (CASE) PhD studentship under the supervision of Dr Simon Woods and Dr Janice McLaughlin of the Policy Ethics and Life Sciences Research Centre, School of Geography, Politics and Sociology, Newcastle University, in collaboration with network of excellence TREAT-NMD. The principal objective of this studentship is to explore what frames the approach taken by boys and young men with Duchenne muscular dystrophy to participating in medical research. The studentship is £18000 (tbc) per annum for 3 years (plus home fees). Preference will be given to applicants who have a Masters level degree and/or relevant research experience and training. Closing Date for Applications is Monday, 22nd June 2009.
For further details


Courses & Educational Initiatives
2009 Goldrain Courses in Clinical Cytogenetics and in Prenatal Genetic Diagnosis
Fouth Goldrain Course in Clinical Cytogenetics
Venue: South Tyrol, Italy
Date: 30 August - 2 September 2009

The lectures are aimed at both clinicians and cytogeneticists who have strong mutual interests. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in laboratory and/or clinical cytogenetics. Besides the lectures, there is room for discussions, practical work on databases, student presentations, and a final non-compulsory multiple-choice examination.
For further details

First Goldrain Course in Prenatal Genetic Diagnosis
Venue: South Tyrol, Italy
Date: 20 September - 24 September 2009

The lectures are aimed at obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. Participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. The course will consist of lectures, discussions, practical work on databases, student presentations, and a non-compulsory multiple-choice examination.
For further details

European School of Haematology Training Course in Clinical Management of Disorders of Iron Metabolism
The European School of Haematology is offering a Training Course in Clinical Management of Disorders of Iron Metabolism taking place from 2-4 July 2009 in Albufeira, Portugal.
For further details


What's on Where?
The Fourth Eastern European Conference on Rare Diseases and Orphan Drugs
Date: 13-14 June 2009
Venue: Plovdiv, Bulgaria

“Together for an Integrative Approach to Rare Diseases”. Supported and co-funded by a grant from the European Union, in the framework of the Public Health Programme this conference presents rare diseases as a common issue at the national and European level requiring an integrated approach involving all stakeholders.
For further details

Porphyrins and Porphyrias 2009
Date: 14-18 June 2009
Venue: Stockholm, Sweden

The scientific program will cover the latest developments in the field of heme-related disorders. The meeting will include plenary sessions, oral presentations and poster presentations. Contributions will be made from basic scientists, molecular biologists, laboratory and clinical academicians, clinical researchers and physicians working in the field of heme metabolism and heme-related disorders.
For further details

EuroGentest symposium
Date: 18-19 June 2009
Venue: Leuven, Belgium

Topics include: accreditation according to ISO 15189, accreditation bodies in Europe and the world, External Quality Assessment schemes, IT solutions to support your quality management system, and experiences from people working in an accredited laboratory or preparing for accreditation.
For further details

Neonatal Screening - A Chance to Life Conference
Date: 18-19 June 2009
Venue: Bucharest, Romania

The non-profit group A Child’s Chance, along with the Institute for Mother and Child Care Alfred Rusescu, the Romanian Pediatric Society, the Romanian Medical Genetics Society, and the Romanian Neonatology Association are hosting the conference Neonatal Screening - A Chance to Life, aiming to improve the diagnosis and treatment of metabolic disorders in Romania. Several international experts will be present at this event.
For further details

5th International Congress on Shwachman-Diamond Syndrome
Date: 19-20 June 2009
Venue: Amsterdam, Netherlands

The 5th International Congress on Shwachman-Diamond Syndrome provides a unique opportunity for clinicians, researchers, and patient organisation representatives from around the world to meet.
For further details

Balkan Congress for Rare Diseases
Date: 26-27 June 2009
Venue: Cluj-Napoca, Romania

This conference will address issues in diagnosing and managing rare diseases in the region and will explore ways to increase European collaboration.
For further details

2nd ELA Research Foundation Congress
Date: 26-27 June 2009
Venue: Luxembourg

“Therapeutic challenge in white matter diseases” is the theme of this congress that will bring together leading international experts in leukodystrophies, myelin biology, neuroimaging, stem cell research and gene therapy to share and discuss recent advances and cutting-edge science in these fields with the ultimate goal to fight and eventually find a cure for the disabling leukodystrophies and myelin diseases.
For further details

Seventh International Progressive Supranuclear Palsy Medical Workshop
Date: 7 July 2009
Venue: London, UK

This year’s event is entitled “The Progressive Supranuclear Palsy Jigsaw – Corners and Edges”. Topics include aetiology, diagnosis, treatment, and palliation.
For further details

Cornelia de Lange Syndrome World Conference
Date: 23 July 2009
Venue: Brighton, UK

This event is part of the Cornelia de Lange Syndrome World Conference and is aimed at teachers, support staff and health professionals who work with children and adults with intellectual disability, autism spectrum disorder and genetic syndromes. The focus is on identifying and responding to the critical personal and family issues that affect the day to day quality of life of all people with intellectual disability. Cornelia de Lange syndrome will be highlighted.
For further details

Treatment Options in Phenylketonuria and Related Pediatric Neurotransmitter Disorders
Date: 29 August 2009
Venue: San Diego, California

Key Topics include challenges in the pharmaceutical treatment of PKU and treatment of paediatric neurotransmitter disorders.
For further details

Genetics and Genomics of Vascular Disease Workshop
Date: 13-16 September 2009
Venue: Hyannis, MA

The programme will present cutting edge research in areas like genome wide association studies in human populations, mouse QTL mapping of vascular phenotypes, and pathogenesis of vascular and developmental diseases using human patients and mouse models.
For further details

European Working Group on Rett Syndrome – 2009 Meeting
Date: 17-18 September 2009
Venue: Stresa, Italy

An opportunity to discuss Rett syndrome-related science, to find collaborators for grant applications, and to exchange reagents and ideas. Moreover, the close contact with the parents associations should also help to focus better on the scientific problems that need to be resolved to find a cure for patients. Abstract deadline: 15 June 2009.
For further details

British Paediatric Neurology Association: Rare Disorders Symposium
Date: 29 September 2009
Venue: Harrogate, England

A stand-alone satellite symposium on rare disorders will take place as part of the 8th Paediatric Neurology Conference. Further information to appear shortly.
For further details

Fourth International Conference on Birth Defects and Disabilities in the Developing World
Date: 4-7 October 2009
Venue: New Delhi, India

The theme of the Fourth International Conference is "Translating Research into Cost-effective Services for the Care and Prevention of Birth Defects, Preterm Birth and Consequent Disabilities".
For further details

EPPOSI: 10th Workshop on Partnering for Rare Disease Therapy Development
Date: 26-27 October 2009
Venue: Brussels, Belgium

The topic of this year’s workshop of the European Platform for Patients’ Organisations, Science and Industry is “10 years after the adoption of the EU Orphan Medicines Regulation: Where do we go? Three key themes will be addressed: “What is the impact of the economic crisis on the field of rare diseases – and what is the vision on further progress in R&D, diagnosis and patient care? Building on the public policy base of the last 10 years: how to advance policies in the next five years? Rare cancers: specific challenges within rare diseases. Consult the draft programme
For further details

TREAT-NMD/NIH International Conference
Date: 17-19 Nov 2009
Venue: Brussels, Belgium

The aim of the meeting is to share progress in the area of translational medicine in inherited neuromuscular diseases and set the future collaborative agenda. This conference will build on achievements of the NIH and TREAT-NMD. It will be a highly interactive meeting with a strong focus on the key issues surrounding "trial readiness" in the neuromuscular field.
For further details

ESF-UB Conference in Biomedicine: Rare Diseases II: Hearing and Sight Loss
Date: 22-27 November 2009
Venue: Sant Feliu de Guixols, Spain

A conference of the European Science Foundation. Details to follow.
For further details

18th International Workshop on Vascular Anomalies
Date: 21-24 April 2010
Venue: Brussels, Belgium

The programme for this workshop will be available soon.
For further details

5th European Conference on Rare Diseases 2010
Date: 13-15 May 2010
Venue: Cracow, Poland

Details for this conference will be available soon.


Press & Publications
Several recent titles target specific rare disease groups
Neurocutaneous Disorders: Phakomatoses & Hamartoneoplastic Syndromes

Ruggieri, M; Pascual Castroviejo, I; Di Rocco, C -Eds.
Springer, 2008
ISBN: 978-3-211-21396-4
Neurocutaneous diseases are a wide group of conditions that affect the nervous system but appear as lesions of the skin. Recent insights into their cellular, biochemical and molecular genetic bases have shown the essential need for a new nosology as well as updated genotype-phenotype correlations. This book provides a practical, comprehensive guide to the recognition, investigation and management of more than 60 recognised phakomatoses.

Progress in Analysing Disorders of Sexual Development

Ogata, T -Ed.
Karger, 2008
ISBN 978-3-8055-9003-7
This text summarises the current state of clinical and molecular research in the field. A new terminology for human disorders of sexual development (DSD) has recently been proposed at an International Consensus Meeting. In the introductory chapter, this terminology as well as the current approach to the management of DSD patients is presented.

Diagnosis and Management of Pituitary Disorders

Swearingen, B; Biller, BMK -Eds.
Humana Press, 2008
ISBN: 978-1-58829-922-2
A detailed update on current diagnostic and therapeutic techniques useful in the management of a broad spectrum of pituitary disorders, this work reflects the multidisciplinary approach needed for patients with disorders of the pituitary gland, with contributions from both endocrinologists and neurosurgeons, as well as specialty contributions from radiologists, ophthalmologists, pathologists, radiation oncologists, and neurologists.

Comprehensive Pediatric Nephrology

Author: Denis F. Geary, Franz Schaefer
Mosby, 2008
ISBN-10: 0323048838
International experts provide the latest on epidemiology, diagnosis, investigations, management, and prognosis for a full range of paediatric kidney disorders.


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