There were presentations from the 12 members of the medical panel (three international), and 15 patients attended, some with their families.  The main research aims of this conference were to learn about advances in the disorder, to discuss the relevance to melorheostosis of recent findings in related skeletal conditions, and to decide in which direction further research should go.  Since this conference included patients as well as researchers it provided a novel opportunity to meet melorheostosis sufferers from the UK who had not been to the previous meetings abroad.  We endeavoured to help them with their medical problems and we ourselves learnt a lot about melorheostosis.

The proceedings were opened by Andrew Carnell, Chairman of the Melorheostosis Association UK, who welcomed the participants and described the successful fund raising activities and the support for research.  Paul Wordsworth (Oxford) introduced the first session of the scientific meeting by a short description of the clinical and genetic aspects of melorheostosis and its management.  Geert Mortier (Belgium), Michael Whyte (USA) and Yung Zhang (Oxford) then gave updates of the results of their research.  Michael Whyte and Geert Mortier had examined the DNA obtained from patients at previous USA meetings: their results were largely in agreement and would soon be submitted for publication.  The main conclusions remain unchanged, that is that mutations in the LEMD3 gene can be found in osteopoikilosis (and the Bushke-Ollendorf syndrome) and also in melorheostosis when the two disorders are combined; but that when melorheostosis occurs on its own no such mutations can be found.  The relationship between osteopoikilosis and melorheostosis remains obscure, and the possibility that in melorheostosis the distribution of the bone (and soft tissue) lesions is related to post-zygotic mutations has not been excluded.  Geert Mortier re-emphasised the central importance of LEMD3 since loss of function in this gene will (in theory) result in transcriptional activation of TGFß, activin or BMP-responsive promoters.

In melorheostosis ectopic mineralisation can occur in the soft tissues (and can be extensive).  The reason for this is unknown.  Clues may be obtained from the study of other disorders with ectopic mineralization.  This is particularly relevant when the ectopic tissue is bone (i.e. ectopic calcification).  Yun Zhang described the activating mutations in the ANKH gene, which leads to chondrocalcinosis, and current work on the structure of the ANKH protein.  She also updated her work on the LEMD3 gene and introduced the relevance of the described mutation in the ACVR1 gene in FOP, where ectopic ossification is a major part of the phenotype.

Recent discoveries have re-emphasised the importance of the Bone Morphogenetic Proteins (BMPs), which belong to the TGFß superfamily, and their receptors in the control of normal and abnormal bone formation.  The ways in which BMPs produce their cellular effects by signalling is complex but can be studied in the laboratory, and Philippa Hulley (Oxford) described how this could be done.

In the second session of the meeting Matthew Brown (Australia and Oxford) described the multinational work which led up to the discovery of the activating mutation in ACRV1, a BMP receptor, in fibrodysplasia ossificans progressiva and explained a project for generating LEMD3 mutants in mice using a well-established method for random mutagenesis.  Dealing more directly with melorheostosis Nick Athanasou (Oxford) described the changes in the skeletal and extraskeletal tissues in melorheostosis and reviewed those rare conditions labelled as osteoscleroses which need to be distinguished from it.  David Wilson (Oxford) emphasised the radiological changes which were characteristic of melorheostosis.  These were wavy hyperostosis in a peripheral location, single limb or dermatome distribution crossing the joint, sometimes endosteal hyperostosis and/or soft tissue mineralization.  Usefully he pointed out the role of isotope bone scanning to define which parts of the skeleton are affected and the indications for MRI scans in this disease.

Since melorheostosis is so rare there may be a considerable delay in diagnosis.  The disorder itself may present in a number of different ways which require different treatments (Paul Wordsworth, Oxford).  Localised bone enlargement can cause pain and loss of movement in a nearby joint.  Involvement of the soft tissues can lead to contractures.  Where pain is a problem, appropriate analgesia is important and where disability is severe specialised rehabilitation is important.  Close cooperation with an experienced surgeon is essential to control deformity and contractures (Martin McNally, Oxford).  The Ilizarov method can be particularly useful where complex deformity is combined with asymmetry.  Such operations should not be undertaken lightly.

One important aspect of this meeting was to give sufficient time to the patients and indeed this occupied much of the remaining space.  Fourteen patients were seen individually by the medical panel (Martin McNally, Geert Mortier, Roger Smith, Michael Whyte and Paul Wordsworth).  Radiographs were available (or had previously been seen) in most cases.  There was a wide variety of phenotypes.  With their consent blood was taken for diagnostic purposes and mutational analysis.

In the concluding (third) session Paul Wordsworth (Oxford) and Jim Triffitt (Oxford) briefly dealt with disorders related to melorheostosis.  Roger Smith (Oxford) then summarised the day’s meeting and thanked all those involved.

On the morning of 12 May members of the medical panel met briefly to discuss future meetings and research. 

It was agreed that meetings should not be held more frequently than every two years, unless there was some spectacular advance, and since the present format seemed to work it should remain essentially unchanged.

So far as future research is concerned it will be most important to construct a melorheostosis registry, and Geert Mortier agreed to lead on this.  Since Ghent and Oxford are close (by Eurostar) some informal meetings could take place.