Various comorbid conditions have been found to be associated with facioscapulohumeral muscular dystrophy (FSHD), including hearing loss, retinal abnormalities, and seizures [1–3]. These conditions are seen primarily in those with more severe, early-onset FSHD [4]. The cause of hearing loss in FSHD is unknown; however, involvement of the stapedius muscles or cochlear dysfunction has been suggested [5]. Symptomatic retinal abnormalities such as Coats disease are rare in FSHD but can lead to blindness if not treated in a timely manner [4]. Current guidelines advise evaluation by an ophthalmologist for children with severe FSHD and for anyone with visual symptoms [6]. Tawil and Van Der Maarel have suggested the involvement of multiple genes or a gene with pleiotropic effects as an explanation for the presence of extramuscular conditions such as hearing loss and retinal vascular abnormality [7]. Previous studies have shown that seizures are more common in childhood-onset FSHD [8, 9].

While several clinical studies have described these comorbidities in individuals with FSHD, there is a lack of population-based studies in the United States (US) on the prevalence of these comorbidities. We report the prevalence of the above-listed comorbidities in individuals with FSHD from the Centers for Disease Control and Prevention (CDC)’s Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet).

Of 726 individuals with FSHD, 548 individuals (344 definite and 204 probable) were included in the study; 17.2% (n = 94) had at least one comorbidity of interest, with 1.5% (n = 8) having more than one. Of the three comorbid disorders evaluated, hearing loss was the most frequent (13.0%; n = 71). Retinal abnormalities (3.6%; n = 20) and seizures (2.0%; n = 11) were reported less frequently. A higher proportion of individuals with definite case status (18.0%) had at least one comorbidity compared to those with probable case status (15.7%). The frequency pattern for the three comorbidities for each case status was similar to that for the full study cohort, with hearing loss being most frequent (14% for definite and 11.3% for probable cases).

The characteristics of the study cohort are presented in Table 1. A slight majority of individuals were male, and most were Non-Hispanic White. Individuals were most frequently employed and had public health insurance.

Table S1 reports the characteristics of individuals with FSHD with hearing loss and individuals with FSHD without a documented comorbidity. Individuals with seizures and/or retinal abnormalities are not included in this table due to small numbers. The distribution of race/ethnicity and sex in this group was similar to that of the full study cohort in Table 1. Individuals with hearing loss most frequently reported being retired and having public insurance. Individuals without a comorbidity most frequently reported being employed and privately insured.

Overall, median age at comorbidity diagnosis was highest for retinal abnormalities and lowest for seizures (Figure 1). Additionally, ages of comorbidity diagnosis for the three comorbidities combined and for hearing loss specifically were more frequently > 40 years, followed by age group 0–20 years. For probable case status, median (IQR) ages at diagnosis for hearing loss [47.1 (35.0–68.8)], retinal abnormalities [68.9 (64.2–73.8)], and seizures [34.7 (24.3–86.2)] were higher than those for definite case status [43.2 (5.8–65.3); 54.7 (25.0–63.1); and 8.4 (1.0–34.5), respectively].

A substantial minority of our FSHD study cohort had hearing loss, while fewer had seizures and retinal abnormalities, consistent with some previous studies that included both childhood and typical-onset patients with FSHD [8, 9, 12]. Individuals with childhood-onset FSHD are more likely to experience hearing or visual impairment than those with typical-onset FSHD [12–14]. Studies have reported median ages of ≤ 10 years old for diagnoses of hearing loss and retinal abnormality in FSHD [15, 16], while median ages at these diagnoses occurred in adulthood in our study. However, several studies [8, 12, 16] examined only childhood-onset FSHD, while ours was not restricted by age at FSHD diagnosis.

Frequency of hearing loss among individuals with FSHD in previous studies ranged widely (8% to 56%) [4, 8, 9, 16]. Evidence suggests that the diagnosis of hearing loss is not more prevalent in individuals with FSHD with typical onset (> 10 years) when compared to the general population [13, 17]. The hearing loss frequency in our FSHD cohort (13.5%) is comparable to that reported in the US population of individuals age ≥ 12 who have bilateral hearing loss (12.7%) and bilateral or unilateral hearing loss (20.3%) [18]. Although overall frequencies are similar, mean or median ages at diagnosis differ; the median age at hearing loss in our study was 46.5 years, and the US general population mean was 74 years [19]. This difference in age could be explained by our data showing 25% of individuals with hearing loss onset age < 20 years and 49% > 40 years (Table S1).

Our result for retinal abnormalities prevalence is similar to a study reporting Coats disease, a severe retinovascular disease, in 3.6% of 28 individuals with childhood-onset FSHD [9]. Another study reported symptomatic Coats disease in 0.8% of 396 individuals with FSHD [15]. However, retinal abnormalities in our study were not limited to Coats disease. The estimated prevalence of retinopathy reported in the US general population (3.4%) is similar to our study cohort’s retinal abnormalities frequency [20].

Several studies have reported high frequencies (7.1%–44%) of epilepsy in FSHD [3, 8, 9, 14]; however, due to a lack of sufficient data on seizure types in our study cohort, we were unable to ascertain the number of individuals with epilepsy, and therefore cannot directly compare our findings to these studies.

Limitations of our study include the lack of comprehensive data available about some comorbid conditions documented for some individuals (e.g., seizure types, extent of hearing loss). Also, the date/age at comorbid disease diagnosis in our dataset may not always be an accurate timepoint of onset or first diagnosis. Additionally, not all individuals in our study cohort had likely undergone hearing tests.

These results demonstrate that hearing loss and retinal abnormalities were just as prevalent in our FSHD study cohort as they are in the US general population, while seizures were more frequent. Our results on the prevalence of comorbid conditions among individuals living with FSHD help provide a better understanding of disease burden and support recommendations for early ophthalmological and audiometry screening for individuals with severe FSHD [6]. Further population-based studies are needed to investigate whether these comorbidities are more frequent in individuals with childhood-onset FSHD.

Supporting Information

Additional supporting information can be found online in the Supporting Information section. Table S1: Sociodemographic characteristics among individuals with FSHD with hearing loss and those with no comorbidity in MD STARnet.