In a new comprehensive analysis of the US National Registry for facioscapulohumeral muscular dystrophy (FSHD), findings revealed gender disparities in pediatric-onset FSHD, which affects 20% of cases, showing that girls experienced more severe outcomes. These findings support the notion that pediatric-onset FSHD is part of the clinical spectrum of FSHD and suggest that girls are more severely affected by pediatric-onset FSHD than boys.1
Investigators identified a total of 166 patients with genetically confirmed FSHD type 1 or type 2, with an average of 10.4 years (median 9 years, range 0-21) of follow up surveys. In the registry, patients with between 1 to 3 copies of D4Z4 repeats were diagnosed at a younger age than those with more than 4 D4Z4 repeats (P <.001), and progressed to wheelchair use at a younger age (P <.001), which is consistent with the previous literature.
Top Clinical Takeaways
- In pediatric-onset FSHD, affecting 20% of cases, girls experienced more severe outcomes than boys, which reveals gender disparities.
- Patients with 1 to 3 copies of D4Z4 repeats are diagnosed at a younger age and progress to wheelchair use earlier than those with more than 4 repeats, aligning with previous literature.
- The study, the largest analysis of pediatric FSHD data in the US, highlights the need for larger, prospective studies to better understand disease progression and potential sex differences for improved clinical care and trial design.
These findings from the analysis were presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 3-6, in Orlando, Florida, by lead author Natalie Katz, MD, PhD, an assistant professor of pediatrics at Duke University Medical Center, and colleagues. In this study, investigators prospectively collected data from participants in the US National Registry for FSHD who received a diagnosis at 18 years or older to analyze disease progression in this population. Authors defined early-onset of FSHD in this population as a diagnosis of at least 10 years of age.
READ MORE: Viltolarsen Shows Significant Pulmonary Function Gains in Ambulant and Nonambulant DMD
In an analysis that separated the participants by sex, investigators observed that girls were diagnosed at a significantly younger age than boys (P <.001), independent of D4Z4 repeat size (P <.001), and were more likely to report diagnosis at least 10 years of age (P <.001). In addition, girls were more likely to report facial weakness as their initial symptom (P = .001) and girls with early-onset FSHD progressed to wheelchair use at a younger age than boys (P <.001).
All told, this was the largest analysis of prospectively collected data from patients with FSHD in the US diagnosed during their pediatric years to date. Authors recommended larger, prospective studies in the future to further understand disease progression in pediatric FSHD and if there are any sex differences in disease severity, which they noted could have implications for clinical care and trial stratification.
In a nationwide cohort study published in Neurology, findings showed that pediatric FSHD has a slowly progressive but variable course over 2 years of follow-up. Despite the observed disease progression, investigators noted that an improvement in functional capacity may still occur later in childhood. In addition, authors noted that the most common symptoms experienced by pediatric patients with FSHD were pain, fatigue, and a decreased quality of life. These results may be used to counsel patients and represent baseline measures for treatment trials in pediatric FSHD.2
Among 20 pediatric patients with FSHD, investigators observed that symptoms showed as slowly progressive, with mean FSHD clinical score increasing from 2.1 to 2.8 (P = .003) at 2-year follow-up. At baseline, 16 patients had facial weakness. After 2 years, facial weakness was observed in 19 patients. Between baseline and follow-up, authors observed no change in muscle strength in the participants and reported improvement in functional exercise capacity, measured with the 6-minute walk test. Researchers also noted that systemic features were infrequent and nonprogressive. Additionally, weakness-associated complications such as lumbar hyperlordosis and dysarthria were reported as common and had an increase in prevalence during follow-up.
Click here for more coverage of MDA 2024.
REFERENCES
1. Katz N, McHan L, Tawil R, McDermott M, Statland J. Pediatric FSHD in the US: Results from the US National Registry for FSHD. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Poster T435.
2. Dijkstra JN, Goselink RJM, van Alfen N, et al. Natural History of Facioscapulohumeral Dystrophy in Children: A 2-Year Follow-up. Neurology. 2021;97(21):e2103-e2113. doi:10.1212/WNL.0000000000012882
