Edition of 21 December 2012

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.

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.

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.

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.

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).

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.

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.

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.

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.