A Comprehensive Review on Stone Man Syndrome

Review Article

Abstract

Stone Man Syndrome also called as Fibrodysplasia ossificans progressiva (FOP) represents one of the most severe disorders of heterotopic ossification in humans, characterized by progressive transformation of soft tissues into bone. This rare genetic condition, affecting approximately 1 in 2 million individuals globally, results from mutations in the ACVR1 gene, which encodes the bone morphogenetic protein (BMP) type I receptor. The hallmark features include malformation of the great toes present at birth and progressive heterotopic ossification that typically begins in childhood. The heterotopic ossification follows a characteristic anatomic pattern, starting in the dorsal, axial, cranial, and proximal regions of the body, subsequently proceeding in a peripheral, ventral, and distal direction. Flare-ups often occur spontaneously or following trauma, leading to inflammation and subsequent bone formation. Early diagnosis remains crucial yet challenging, with many patients initially misdiagnosed with other conditions. Recent advances in understanding the molecular pathways involved in FOP have led to promising therapeutic strategies, including the development of ACVR1 inhibitors and the recent FDA approval of Palovarotene (SOHONOS). Management primarily focuses on preventing complications and maintaining quality of life through multidisciplinary care. Despite these advances, significant challenges remain in developing effective treatments that can halt or reverse disease progression. This paper explores the current knowledge of FOP's pathogenesis, clinical manifestations, diagnostic approaches, and therapeutic strategies, emphasizing the importance of early recognition and appropriate management to optimize patient outcomes.