Natural History of Facioscapulohumeral Dystrophy in Children: A 2-Year Follow-up

Abstract

Background and objectives: Data on the natural history of facioscapulohumeral dystrophy (FSHD) in childhood are limited and critical for improved patient care and clinical trial readiness. Our objective was to describe the disease course of FSHD in children.

Methods: We performed a nationwide, single-center, prospective cohort study of FSHD in childhood assessing muscle functioning, imaging, and quality of life over 2 years of follow-up.

Results: We included 20 children with genetically confirmed FSHD who were 2 to 17 years of age. Overall, symptoms were slowly progressive, and the mean FSHD clinical score increased from 2.1 to 2.8 (p = 0.003). The rate of progression was highly variable. At baseline, 16 of 20 symptomatic children had facial weakness; after 2 years, facial weakness was observed in 19 of 20 children. Muscle strength did not change between baseline and follow-up. The most frequently and most severely affected muscles were the trapezius and deltoid. The functional exercise capacity, measured with the 6-minute walk test, improved. Systemic features were infrequent and nonprogressive. Weakness-associated complications such as lumbar hyperlordosis and dysarthria were common, and their prevalence increased during follow-up. Pain and fatigue were frequent complaints in children, and their prevalence also increased during follow-up. Muscle ultrasonography revealed a progressive increase in echogenicity.

Discussion: FSHD in childhood has a slowly progressive but variable course over 2 years of follow-up. The most promising outcome measures to detect progression were the FSHD clinical score and muscle ultrasonography. Despite this disease progression, an improvement on functional capacity may still occur as the child grows up. Pain, fatigue, and a decreased quality of life were common symptoms and need to be addressed in the management of childhood FSHD. Our data can be used to counsel patients and as baseline measures for treatment trials in childhood FSHD.

Figure 1. Flow Diagram of Patient Inclusion in Previously Published Baseline Study (Gray) and Current 2-Year Follow-up Study (Blue)

The 8 children for whom only an electronic health record review had been performed at baseline were not invited for follow-up. However, their baseline characteristics, including the mean age at time of baseline examination, age at onset of symptoms, age at time of diagnose, sex, and mean number of D4Z4 repeats, were similar to those of the group of children who were included in this follow-up study.

Figure 2. Muscle Function and Imaging in Individual Patients Over 2 Years

(A) Facioscapulohumeral dystrophy (FSHD) clinical score (0–15), (B) performance on Motor Function Measure (MFM; 0%–100%), (C) performance on 6-minute walk test (6MWT; z score, the number of SDs of the mean for sex and age in healthy individuals), and (D) muscle ultrasound mean echogenicity (mean z score) at baseline and 2-year visit.

Figure 3. Muscle Ultrasound Results

(A) Mean z score of quantitative muscle ultrasound measuring echogenicity. This shows the combined muscle ultrasound measurements of 9 participants at the 2-year follow-up. (B) Distribution of the measured muscles at baseline and follow-up by qualitative analysis using Heckmatt scores and (C) by quantitative analysis using z scores.