BackgroundValosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget’s disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype–phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype–phenotype correlations.MethodsDescriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene.ResultsTwo hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8±9.6 years and mean age of onset 45.6±9.3 years. Mean diagnostic delay was 7.7±6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8±7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC <70% and being a full-time wheelchair user were associated with death.ConclusionThis study expands the knowledge on the phenotypic presentation, natural history, genotype–phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.

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ObjectiveWe provide succinct, evidence-based and/or consensus-based best practice guidance for the cardiac care of children living with Duchenne muscular dystrophy (DMD) as well as recommendations for screening and management of female carriers of mutations in theDMD-gene.MethodsInitiated by an expert working group of UK-based cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK-cardiologists, consensus was reached on these best-practice recommendations for cardiac care in DMD.ResultsThe resulting recommendations are presented in the form of a succinct care pathway flow chart with brief justification. The guidance signposts evidence on which they are based and acknowledges where there have been differences in opinion. Guidelines for cardiac care of patients with more advanced cardiac dystrophinopathy at any age have also been considered, based on the previous published work of Quinlivanet aland are presented here in a similar format. The recommendations have been endorsed by the British Cardiovascular Society.ConclusionThese guidelines provide succinct, reasoned recommendations for all those managing paediatric patients with early or advanced stages of cardiomyopathy as well as females with cardiac dystrophinopathy. The hope is that this will result in more uniform delivery of high standards of care for children with cardiac dystrophinopathy, so improving heart health into adulthood through timely earlier interventions across the UK.