Autoimmune Comorbidities as Modifiers of Phenotypic Heterogeneity in Facioscapulohumeral Dystrophy

Figures

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  FIGURE 1. Study design and spectrum of autoimmune diseases in the FSHD1 cohort. (A) Breakdown of patients and distribution of autoimmune diseases across CCEF categories. Patients were classified according to the Comprehensive Clinical Evaluation Form (CCEF) into categories A (typical FSHD phenotype), B (incomplete phenotype), C (asymptomatic/pauci‐symptomatic), and D (atypical phenotype). The number and subtype distribution of autoimmune diseases identified within each category are shown. (B) Distribution of autoimmune diseases identified in the FSHD1 cohort. A total of 96 autoimmune conditions were identified in 82 patients. The table summarizes the number of cases, prevalence among autoimmune patients, and prevalence within the entire FSHD1 cohort. The pie charts illustrate the relative contribution of each autoimmune disease. Hashimoto's thyroiditis was the most common autoimmune comorbidity, followed by autoimmune diabetes, atopic dermatitis, myasthenia gravis (MG), primary biliary cholangitis (PBC), and psoriasis. Less frequent conditions included idiopathic inflammatory myositis (IIM), Sjögren's syndrome, Addison's disease (AD), vitiligo, alopecia, multiple sclerosis (MS), chronic…

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  FIGURE 2. Comparison of demographic, genetic, clinical, and phenotypic characteristics between FSHD1 patients with and without autoimmune disease. (A) Age at examination. (B) Age at disease onset. (C) D4Z4 repeat unit (RU) number. (D) Distribution of D4Z4 RU categories (1–3, 4–6, and 7–10 RU). (E) Distribution of CCEF categories. (F) FSHD clinical severity score. Data are presented as mean ± SD. Statistical significance was assessed using unpaired t‐tests or Fisher's exact tests, as appropriate. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

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  FIGURE 3. Stratified demographic, genetic, and clinical analyses according to CCEF category and autoimmune disease status. (A) Age at examination according to autoimmune status within each CCEF category. (B) D4Z4 repeat unit number according to autoimmune status within each CCEF category. (C) Distribution of D4Z4 RU categories within each CCEF category. (D) FSHD severity score according to autoimmune status within each CCEF category. Data are presented as mean ± SD. *p < 0.05, **p < 0.01.

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  FIGURE 4. Relationship between D4Z4 repeat unit number and FSHD severity according to autoimmune disease status. Scatter plot showing FSHD severity score as a function of D4Z4 repeat unit (RU) number in FSHD1 patients with and without autoimmune disease. A small horizontal jitter was applied to the data points to reduce overlap and improve visualization. Linear regression lines and 95% confidence intervals are shown for each group.

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  FIGURE 5. Proposed model of disease modifiers across the D4Z4 repeat size spectrum in FSHD1.