Subacromial Impingement Syndrome (SIS): Concepts in Pathophysiology, Genetics, Diagnosis, and Evidence-Based Management

Abstract

Background: Subacromial impingement syndrome/pain syndrome (SIS/SAPS) is one of the most common causes of shoulder pain and functional limitation, affecting both the general population and individuals exposed to repetitive overhead activity. Despite extensive research, the pathogenesis, diagnostic criteria, and optimal management strategies for SIS/SAPS remain subjects of ongoing debate. Emerging evidence suggests that genetic susceptibility may contribute to individual variation in disease development and clinical presentation. Objective: The aim of this review was to analyze current concepts regarding the etiology, clinical presentation, diagnostic approaches, and treatment strategies for SIS/SAPS, with emphasis on contemporary evidence, evolving perspectives, and recently identified genetic and molecular contributors. Methods: A literature review was conducted mainly using publications indexed in Scopus, Web of Science, and PubMed. Original research articles, genome-wide association studies, systematic reviews, clinical guidelines, and high-quality randomized controlled trials addressing epidemiology, biomechanics, genetic susceptibility, imaging, conservative management, and surgical treatment of SIS/SAPS were analyzed and synthesized. Results: Current evidence supports a paradigm shift from viewing SIS/SAPS as a purely mechanical disorder to understanding it as a multifactorial clinical syndrome involving anatomical, biomechanical, functional, and genetic factors. Recent genome-wide association studies have identified single nucleotide polymorphisms associated with shoulder impingement and related rotator cuff pathology, implicating pathways involved in tendon and enthesis biology, inflammatory regulation, and pain processing. Clinical examination remains central to diagnosis, while imaging modalities such as radiography, MRI, and functional ultrasound play an adjunctive role in excluding alternative pathologies and guiding management. Conservative treatment—particularly individualized, supervised exercise therapy combined with patient education and load modification—demonstrates superior long-term outcomes compared with isolated interventions such as corticosteroid injections. Recent high-quality trials question the routine use of surgical subacromial decompression in the absence of clear structural pathology. Conclusion: SIS/SAPS should be approached as a complex, heterogeneous condition influenced by both environmental and genetic factors, requiring patient-centered, evidence-based management. Incorporating genetic and biological insights alongside functional assessment and rehabilitation-focused treatment may enhance risk stratification and therapeutic decision-making. Judicious use of imaging and surgery remains essential to optimize clinical outcomes.