Facioscapulohumeral dystrophy in children: design of a prospective, observational study on natural history, predictors and clinical impact (iFocus FSHD)

Abstract

BackgroundFacioscapulohumeral 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/designThis 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.DiscussionThe 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.Trial registrationclinicaltrials.gov NCT02625662.

The best care for children with facioscapulohumeral dystrophy

“…4 Remarkably, Steel et al report a high prevalence of developmental and mental health complications. This agrees with more recent reports on very early onset FSHD (as cited in Goselink et al 1 ) and contrasts with the former notion that patients with infantile FSHD are 'mentally' typical. 3 Such comorbidities may be neglected in routine assessments, making this a highly significant finding and a clinical priority.…”

“…Estimates of infantile facioscapulohumeral dystrophy (FSHD) vary between cohorts, from 3% to 21% of patients, which may result from population-dependent modifiers and variability on cohort enrolment, medical assessments, and classification procedures. 1 Phenotypically, FSHD has long been perceived as a continuum of features and severity, although an early onset correlates with an increased risk of serious extramuscular comorbidities and a much less favourable prognosis. [2][3][4] Steel et al 5 found similar clinical features and propose reasonable strategies to increase awareness and detection of the devastating, yet potentially manageable effects of FHSD on developing children.…”

Clinical features of facioscapulohumeral muscular dystrophy 1 in childhood

“…Large‐scale projects are now underway to collect data on substantial populations of people with FSHD. These include a patient‐initiated national registry in the UK and a prospective study of all children diagnosed with FSHD in the Netherlands . It is hoped that these will form a solid foundation of evidence on which to base better and more targeted support for individuals with FSHD.…”

“…These include a patient-initiated national registry in the UK 25 and a prospective study of all children diagnosed with FSHD in the Netherlands. 26 It is hoped that these will form a solid foundation of evidence on which to base better and more targeted support for individuals with FSHD. Meanwhile, paediatric neurology services should be aware that good care for children and young people with FSHD1 goes far beyond dealing with their muscular impairments.…”

The Role of Muscle Imaging in the Diagnosis and Assessment of Children with Genetic Muscle Disease

“…118,119 More severe infantile forms can also present with rapid progression of weakness, marked hyperlordosis, sensorineural hearing loss, and retinal vasculopathy. [120][121][122] FSHD1 is caused by a distinctive molecular mechanism affecting the subtelomeric region of chromosome 4q35 leading to DUX4 expression. 123,124 A large number of muscle MRI studies have been performed in patients with FSHD.…”