Fibrodysplasia Ossificans Progressiva: The present and future of understand ing and treatment Samantha He January 15, 2009 Med ical Genetics. Prof. liu MBBS, Fudan University ABSTRACT Fibrodysplasia ossificans progressiva(FOP)is a disabling d isease that is caused by episod ic heterotopic ossification(HO)and advances in a pattern similar to embryonic development. The molecular pathway that causes the disease has been identified to involve bone morphogenic proteins and the associated activin type I receptor. A heterozygous point mutation in the type 1 receptor of FoP patients has been identified Currently there are no specific treatments to prevent or reduce HO growth, although experimental drugs were tested with favorable results, such the signal transduction inhibitor LD-193189. However, the battle against FOP is far from over as there are still questions related to FoP disease progression that remains unanswered INTRODUCTION One of the most catastrophic cond itions known to man kind, fibrodysplasia ossificans progressiva(FOP)has been a puzzle to doctors and researchers since the first recorded description some 250 years ago by John Ferke [41 below. The disease is characterized by heterotopic ossification(HO) of muscles, connective tissue, joints, aponeuroses, ligaments and fascia[4]. Although the bone morphogenic protein(BMP) pathway was identified, the genetics of the disease remained a mystery. In 2006,a heterozygous point mutation in FOP patients was found in several stud ies done in different countries. This mutation causes the activin type I receptor(ACVRI) to be constitutively active [6, 7]. Knowing the genetic makeup of the disease is important for an early diagnosis, espec ially for FoP because the misd iagnosis rates can be as high as 90%[5]. Although the genetic advancements are to be applauded, there are still many mysteries that remain unsolved regarding FOP CLINICAL FEATURES FOP has one of the highest misd iagnosis rates. The reason is the rarity of the disease and how the disease progresses. A FOP patient will look normal upon birth, except for malformed big toes that most doctors without prior experience with FOPFibrodysplasia Ossificans Progressiva: The present and future of understanding and treatment Samantha He January 15, 2009 Medical Genetics, Prof. Liu MBBS, Fudan University ABSTRACT Fibrodysplasia ossificans progressiva (FOP) is a disabling disease that is caused by episodic heterotopic ossification (HO) and advances in a pattern similar to embryonic development. The molecular pathway that causes the disease has been identified to involve bone morphogenic proteins and the associated activin type I receptor. A heterozygous point mutation in the type 1 receptor of FOP patients has been identified. Currently there are no specific treatments to prevent or reduce HO growth, although experimental drugs were tested with favorable results, such the signal transduction inhibitor LD-193189. However, the battle against FOP is far from over as there are still questions related to FOP disease progression that remains unanswered. INTRODUCTION One of the most catastrophic conditions known to man kind, fibrodysplasia ossificans progressiva (FOP) has been a puzzle to doctors and researchers since the first recorded description some 250 years ago by John Ferke [4]1 below. The disease is characterized by heterotopic ossification (HO) of muscles, connective tissue, joints, aponeuroses, ligaments and fascia [4]. Although the bone morphogenic protein (BMP) pathway was identified, the genetics of the disease remained a mystery. In 2006, a heterozygous point mutation in FOP patients was found in several studies done in different countries. This mutation causes the activin type I receptor (ACVR1) to be constitutively active [6,7]. Knowing the genetic makeup of the disease is important for an early diagnosis, especially for FOP because the misdiagnosis rates can be as high as 90% [5]. Although the genetic advancements are to be applauded, there are still many mysteries that remain unsolved regarding FOP. CLINICAL FEATURES FOP has one of the highest misdiagnosis rates. The reason is the rarity of the disease and how the disease progresses. A FOP patient will look normal upon birth, except for malformed big toes that most doctors without prior experience with FOP