Facioscapulohumeral Dystrophy in Childhood: A Nationwide Natural History Study

Abstract

ObjectiveFacioscapulohumeral dystrophy (FSHD) is one of the most frequent heritable muscular dystrophies, with a large variety in age at onset and disease severity. The natural history and molecular characteristics of FSHD in childhood are incompletely understood. Our objective is to clinically and genetically characterize FSHD in childhood.MethodsWe performed a nationwide, single‐investigator, natural history study on FSHD in childhood.ResultsMultiple‐source recruitment resulted in 32 patients with FSHD (0–17 years), leading to an estimated prevalence of 1 in 100,000 children in The Netherlands. This series of 32 children with FSHD revealed a heterogeneous phenotype and genotype in childhood. The phenotypic hallmarks of FSHD in childhood are: facial weakness with normal or only mildly affected motor performance, decreased functional exercise capacity (6‐minute walk test), lumbar hyperlordosis, and increased echo intensity on muscle ultrasonography. In addition, pain and fatigue were frequent and patients experienced a lower quality of life compared to healthy peers. In contrast to the literature on early‐onset FSHD, systemic features such as hearing loss and retinal and cardiac abnormalities were infrequent and subclinical, and epilepsy and intellectual disability were absent. Genotypically, patients had a mean D4Z4 repeat array of 5 units (range, 2–9), and 14% of the mutations were de novo.InterpretationFSHD in childhood is more prevalent than previously known and the genotype resembles classic FSHD. Importantly, FSHD mainly affects functional exercise capacity and quality of life in children. As such, these results are paramount for counseling, clinical management, and stratification in clinical research. Ann Neurol 2018;84:635–645

Clinical and genetic features of somatic mosaicism in facioscapulohumeral dystrophy

“…Perhaps longitudinal designs can be adopted in future studies to enable such data to be included. Another limitation is that our single-centre study inherently lacks sampling of the broader population context 2 31. However, our inclusion of 35 mosaic participants with FSHD represents the largest cohort to date for such patients, and it bears further emphasis that we used strict inclusion criteria, standardised physical examinations and record collection, as well as CCEF classification of clinical phenotypes.…”

Current Therapeutic Approaches in FSHD

“…In FSHD1, the shorter the number of residual repeats is broadly associated with younger disease onset, overall severity, and increase penetrance. Individuals with 1–3 repeats tend to have earlier onset and more severe muscle weakness and non-muscular manifestations such as symptomatic hearing loss, retinal vascular disease and more likely to develop restrictive lung disease [ 9 ]. Most individuals with FSHD1 have between 4–7 repeats and tend to have, as a group, more moderate disease.…”

Natural History of Facioscapulohumeral Dystrophy in Children

“…A detailed protocol and description of the baseline characteristics can be found elsewhere. 18,19 Clinical Assessments Clinical assessment of the patients was performed by the same examiners at study initiation and after two years of follow-up. The follow-up measurements took place from March 2018 until March 2020, all assessments were performed as a part of this study.…”