B i.e. Progressive form of normal myosites Fibrodysplasia (Myositis) Ossificans Progressiva Patho Histology - It is a rare autosomal dominant (AD) disorder of connective tissue differentiation. - Main pathogenic mechanism is defective regulation of the induction of endochondral ossification - Intense perivascular lymphocytic infiltration into normal skeletal muscles is the earliest featureQ - The proliferating loose myxoid fibrous tissue infiltrates and replaces normally formed fibrous connective tissue and striated muscle - Numerous small blood vessels, cells immunoreactive for S -100 protein and cailagenous foci are scattered among proliferating lesion. - Endochondral ossification is a feature of maturing lesion. Only the absence of normal anatomical orientation differentiates this hetrotropic bone from normal. Otherwise it demonstrates all features of normal bone modeling (i.e., coical & trabecular organization, medullary canal, metaphyseal funneling) and remodeling (i.e., respond to weight bearing stress, resistance to fatigue fracture) - Bone morphogenetic protein - 4 (BMP - 4) is over expressed and Basic fibroblast growth factor which is an extremely potent stimulator of angiogenesis (in vivo) is elevated in urine during acute flare up stage. Clinical features - In myositis ossificans progressiva, the life expectancy is decreased and the commonest causes of death is lung diseaseQ. This autosomal dominant disease is characterized by hetrotropic ossification most commonly involving spine and congenital defomities of hand &feetQ. The disease usually stas before 6 year of ageQ - Moality in fibrodysplasia ossificans progressive (myositis ossificans progressiva) is usually related to restrictive lung disease caused by an inability of chest to expandQ. - Begins in childhood usually before age of 6 yearsQ and becomes evident with in first 10 years of life. - Primary congenital skeletal abnormality is deformity of great toeQ. The toes may be sho, in valgus, monophalangic or have abnormal shaped proximal phalanx. - Begins as painful erythematous subfascial nodule mostly located on posterior aspect of neck & back which gradually calcify & eventually ossify (hetrotropic ossification) - The hetrotropic ossification progress in a axial to appendcular, cranial to caudal and proximal to distal direction. So the most commonly involved site is neck followed by spine & shoulder girdleQ. And same is the order for limitation of motion . - Trauma in form of tripping & falling, immunization, injection or biopsy stimulates new bouts of ossificationQ, and can be catastrophic. - The ossification is irreversible, unlike other forms of hetrotropic ossification. This condition is quite different from myositis ossificans traumaticaQ. - Diaphragm, extra ocular muscles & smooth muscles are characteristically sparedQ - Limitations of jaw mobility , extremely limited chest expnsionQ, reduced lung volumes 44% of normal) but relatively preserved flow rates and scoliosis / hypokyphosis are other feature Life expectancy is decreased and premature death usually result from respiratory failure Alt restrictive lung disease and their complicationsQ or from inanition caused by jaw ankylosis.