Fibrodysplasia Ossificans Progressiva

Abstract

Fibrodysplasia ossificans progressiva (FOP) is characterized by heterotopic ossification and abnormalities of the halluces. At birth, individuals with FOP are normal except for short great toes, which can be medially deviated and monophalangic. Other more variable but common congenital abnormalities include cervical spine malformations (80 %); a short, broad femoral neck (70 %); conductive hearing impairment; short thumb with short 1st metacarpal and/or monophalangism (50 %); and 5th-finger clinodactyly. However, the major problem for these individuals is progressive heterotopic ossifications that follow a characteristic anatomical pattern. They start with swellings, sometimes accompanied by pain and fever, located in muscles, tendons, aponeuroses, and fasciae. The most common sites of early heterotopic ossification are the neck, spine, and shoulder girdle extending over the entire thorax. The age of onset varies between the 1st year of life and the mid-20s, with an average age of 5 years. Ossification generally proceeds in an axial to appendicular direction and from cranial to caudal and proximal to distal. With increasing ossification, movement becomes restricted and eventually results in complete immobility, thoracic insufficiency, and death. Ossification events appear to be often triggered by trauma, including medical intervention such as intramuscular injections, tooth extractions, and diagnostic biopsies. Due to the initial lack of symptoms and the only moderate changes of the great toe, there is usually a major delay in correct diagnosis even after the onset of ectopic ossification.