would perceive as congenital big toe malformations [5, 6]. Generally within the first year, FOP patients will experience their first HO flare up. An HO flare up is like an inflammation of an area that produce tumor like swellings [5]. However, unlike a normal nflammation that subsides, the swellings would eventually turn to bone after receding The HO flare ups are episodic in nature but follow an anatomical pattern generally similar with embryonic development [8]. In addition to episod ic flare ups, if the patient is injured the inflammatory response and subsequent heal ing mechanism could also cause HO of the affected area. FOP swellings are usually misdiagnosed to be cancer or juvenile fibromatosis [5] because just by examining with the naked eye, the diagnosis would need to be confirmed usually by biopsy. Such biopsies would cause more flare ups and ossification of the affected area. Thus to be able to d iagnose the d isease without invasive procedures is a milestone. Before the discovery of the FOP gene, the only ev idence for FOP is HO and the malformed big toe, but by then the patient would have already gone through diagnostic procedures or have lived in a way that unnecessarily caused HO Thus an early diagnosis is crucial for managing the disease BMP PATHWAY Accumulative research showed considerable evidence that the BMP pathway is a suspect for causing FOP symptoms [3]. BMP is a large family of proteins that functions as growth factors first described in relation to cartilage and bone growth [1. BMP signals are mediated by several types of transmembrane receptors, type 1 being acvrI Once bmp binds with aCvRl. signal transduction utilizing downstream molecules such as Smad occurs. Ultimately the goal is to transcribe genes, for example, in chondrocytes causes differentiation and maturation [1]. This process in FOP is disrupted by mutate ACVRI receptor that is constitutively signally downstream molecules, thus heterotopic ossification results ACVRI GENE The gene is located on chromosome 2, q23-q24 [7, 10]. The point mutation changes guanine to adenine, which causes a missense mutation R206H in the glycine- serine(GS) rich domain of the ACVRI protein. The mutation is heritable in an autosomal dominant pattern with complete penetrance. In many studies done around the world, the majority of the FOP pat ients have this type of mutation. However,newer stud ies have shown that other novel mutations such as r202i in gs domain and g 328I in kinase domain also occur [7]. Each of these mutations results in atypical features not observed in typical patients with R206H mutation. This could suggest that FOP has of the most specific disease causing mutations [5]. If that is the case treating FOP gene therapy in the future might be possible due to the specificity of the mutation TREATMENT As of now there are no drugs that target HO. Drugs used are mostly to control inflammations and to make the patient more comfortable during a flare up. The patient needs to take non-steroidal anti-inflammatory drugs throughout his or her life. In addition, if inflammations of major joints occur, a heavy course of cortical steroids are prescribed. The purpose is just to reduce the inflammation in hopes that Ho does notwould perceive as congenital big toe malformations [5,6]. Generally within the first year, FOP patients will experience their first HO flare up. An HO flare up is like an inflammation of an area that produce tumor like swellings [5]. However, unlike a normal inflammation that subsides, the swellings would eventually turn to bone after receding. The HO flare ups are episodic in nature but follow an anatomical pattern generally similar with embryonic development [8]. In addition to episodic flare ups, if the patient is injured the inflammatory response and subsequent healing mechanism could also cause HO of the affected area. FOP swellings are usually misdiagnosed to be cancer or juvenile fibromatosis [5] because just by examining with the naked eye, the diagnosis would need to be confirmed usually by biopsy. Such biopsies would cause more flare ups and ossification of the affected area. Thus to be able to diagnose the disease without invasive procedures is a milestone. Before the discovery of the FOP gene, the only evidence for FOP is HO and the malformed big toe, but by then the patient would have already gone through diagnostic procedures or have lived in a way that unnecessarily caused HO. Thus an early diagnosis is crucial for managing the disease. BMP PATHWAY Accumulative research showed considerable evidence that the BMP pathway is a suspect for causing FOP symptoms [3]. BMP is a large family of proteins that functions as growth factors first described in relation to cartilage and bone growth [1]. BMP signals are mediated by several types of transmembrane receptors, type 1 being ACVR1. Once BMP binds with ACVR1, signal transduction utilizing downstream molecules such as Smad occurs. Ultimately the goal is to transcribe genes, for example, in chondrocytes causes differentiation and maturation [1]. This process in FOP is disrupted by mutated ACVR1 receptor that is constitutively signally downstream molecules, thus heterotopic ossification results. ACVR1 GENE The gene is located on chromosome 2, q23-q24 [7,10]. The point mutation changes guanine to adenine, which causes a missense mutation R206H in the glycine￾serine (GS) rich domain of the ACVR1 protein. The mutation is heritable in an autosomal dominant pattern with complete penetrance. In many studies done around the world, the majority of the FOP patients have this type of mutation. However, newer studies have shown that other novel mutations such as R202I in GS domain and G328I in kinase domain also occur [7]. Each of these mutations results in atypical features not observed in typical patients with R206H mutation. This could suggest that FOP has one of the most specific disease causing mutations [5]. If that is the case treating FOP with gene therapy in the future might be possible due to the specificity of the mutation. TREATMENT As of now there are no drugs that target HO. Drugs used are mostly to control inflammations and to make the patient more comfortable during a flare up. The patient needs to take non-steroidal anti-inflammatory drugs throughout his or her life. In addition, if inflammations of major joints occur, a heavy course of cortical steroids are prescribed. The purpose is just to reduce the inflammation in hopes that HO does not