Pediatric stiff-person syndrome and related disorders: A systematic review.

BACKGROUND

Stiff-person syndrome (SPS) is a rare neuromuscular autoimmune disorder with significant diagnostic and treatment challenges, particularly in pediatric patients. Current understanding of pediatric SPS is limited; therefore, this systematic review aims to analyze the clinical profile, comorbidities, and treatment responses in these cases.

METHODS

A systematic review was conducted following PRISMA guidelines. Literature from five databases was searched up to March 2025, identifying cases of pediatric SPS (age ≤ 20 years). A total of 961 studies were screened, resulting in 49 cases from 41 reports being included. Data on demographics, symptoms, comorbidities, treatment, and outcomes were analyzed.

RESULTS

The 49 cases were distributed across 15 countries, with the highest representation from the USA (44.89%, n = 22). The median age was 12 years (IQR: 7-17), with a nearly equal male-to-female ratio (51.02% male). Comorbidities were present in 55.1% (n = 27), with type 1 diabetes mellitus (18.36%, n = 9) and thyroid dysfunction (14.28%, n = 7) being the most common. SPS subtypes included mainstream SPS (65.3%, n = 32), PERM (22.44%, n = 11), and stiff-limb syndrome (8.16%, n = 4). Benzodiazepines, primarily diazepam, were the most commonly used first-line therapy (51.02%, n = 25). Adjunctive treatments included corticosteroids (24.48%, n = 12), IVIG (18.36%, n = 9), and rituximab (14.28%, n = 7). Persistent symptoms were noted in 26.53% (n = 13) of cases.

CONCLUSION

This study highlights the clinical heterogeneity and autoimmune nature of pediatric SPS. A proposed treatment protocol which may guide clinicians has been formulated.