title: Facioscapulohumeral dystrophy in children: design of a prospective, observational study on natural history, predictors and clinical impact (iFocus FSHD).
abstract: BACKGROUND
  Facioscapulohumeral muscular dystrophy (FSHD; OMIM 158900 & 158901) is a progressive skeletal muscle dystrophy, characterized by an autosomal dominant inheritance pattern. One of the major unsolved questions in FSHD is the marked clinical heterogeneity, ranging from asymptomatic individuals to severely affected patients with an early onset. An estimated 10% of FSHD patients have an early onset (onset before 10 years of age) and are traditionally classified as infantile FSHD. This subgroup is regarded as severely affected and extra-muscular symptoms, such as hearing loss and retinopathy, are frequently described. However, information on the prevalence, natural history and clinical management of early onset FSHD is currently lacking, thereby hampering adequate patient counselling and management. Therefore, a population-based prospective cohort study on FSHD in children is highly needed.
  
  
  METHODS
  This explorative study aims to recruit all children (aged 0-17 years) with a genetically confirmed diagnosis of FSHD in The Netherlands. The children will be assessed at baseline and at 2-year follow-up. The general aim of the study is the description of the clinical features and genetic characteristics of this paediatric cohort. The primary outcome is the motor function as measured by the Motor Function Measure. Secondary outcomes include quantitative and qualitative description of the clinical phenotype, muscle imaging, genotyping and prevalence estimations. The ultimate objective will be a thorough description of the natural history, predictors of disease severity and quality of life in children with FSHD.
  
  
  CONCLUSIONS
  The results of this population-based study are vital for adequate patient management and clinical trial-readiness. Furthermore, this study is expected to provide additional insight in the epigenetic and environmental disease modifying factors. In addition to improve counselling, this could contribute to unravelling the aetiology of FSHD.
  
  
  BACKGROUND
  clinicaltrials.gov NCT02625662.
authors.affiliation: Department of Neurology, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands. Rianne.Goselink@radboudumc.nl.
authors.forename: Rianne J M
authors.initials: RJ
authors.lastname: Goselink
authors.affiliation: Department of Neurology, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Tim H A
authors.initials: TH
authors.lastname: Schreuder
authors.affiliation: Department of Neurology, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Karlien
authors.initials: K
authors.lastname: Mul
authors.affiliation: Department of Neurology, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Nicol C
authors.initials: NC
authors.lastname: Voermans
authors.affiliation: Department of Rehabilitation, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Pelsma
authors.affiliation: Department of Rehabilitation, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Imelda J M
authors.initials: IJ
authors.lastname: de Groot
authors.affiliation: Department of Neurology, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Nens
authors.initials: N
authors.lastname: van Alfen
authors.affiliation: Department of Clinical audiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Franck
authors.affiliation: Department of Op Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Theelen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lemmers
authors.affiliation: Department of Paediatric Neurology, Alberta Children's Hospital, Calgary, Canada.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Mah
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
authors.affiliation: Department of Neurology, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Baziel G
authors.initials: BG
authors.lastname: van Engelen
authors.affiliation: Department of Neurology, Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Corrie E
authors.initials: CE
authors.lastname: Erasmus
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015331:Cohort Studies; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D018740:Genetic Heterogeneity; D005838:Genotype; D009048:Motor Skills / Q000502:physiology; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D010641:Phenotype; D011159:Population Surveillance; D011446:Prospective Studies; D011788:Quality of Life
keywords: Facioscapulohumeral dystrophy; Muscular dystrophies; Neuromuscular diseases; Observational study; Paediatrics