Fibrodysplasia ossificans progressiva (FOP): watch the great toes!

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder and the most disabling condition of heterotopic (extraskeletal) ossification in humans. Extraskeletal bone formation associated with inflammation preceding the osseous conversion usually begins in the first decade, predominantly in the head, neck and shoulders. All patients have malformed great toes. Most patients have a spontaneous mutation of the ACVR1 gene. We report a 17-year-old girl with malformed great toes who had her first episode of heterotopic ossification and impaired mobility of the left hip at the age of 13 years. No inflammatory fibroproliferative masses preceded the onset of heterotopic ossification. Radiographic studies demonstrated myositis ossificans, but failure to associate the great toe malformation with heterotopic ossification led to a failure to diagnose FOP. She underwent repeated and unnecessary operative procedures to remove a recurrent lesion. FOP was finally suspected when the great toe malformation was correlated with the trauma-induced heterotopic ossification. Genetic analysis confirmed the presence of the classic FOP mutation (ACVR1 c.617G>A; R206H). Conclusion This case highlights the importance of examining the great toes in anyone with heterotopic ossification. The association of malformations of the great toe with heterotopic ossification in all cases of classic FOP will lead to prompt clinical diagnosis and the prevention of iatrogenic harm.

Are great toes always abnormal in patients with fibrodysplasia ossificans progressiva?

“…We read with interest a recent paper by Kartal-Kaess and colleagues [3] reporting a child who had episodic and progressive heterotopic ossification along with congenitally malformed great toes. On the basis of these findings, a clinical diagnosis of fibrodysplasia ossificans progressiva (FOP) was made and was confirmed by DNA sequence analysis which revealed the classical FOP mutation in the ACVR1 gene (c.617G>A).…”

“…The report by Kartal-Kaess et al [3] should thus be interpreted with the important caveat that although almost all patients with FOP have great toe abnormalities, the diagnosis can by no means be ruled out in patients with normal great toes. These patients, particularly those presenting after the first decade, can have a FOP variant with milder clinical course.…”

Clinical Utility Gene Card for: Fibrodysplasia ossificans progressiva

“…[6][7][8] There are at least three other forms of MO of which the pathology is largely unknown, including MO Circumscripta, characterized by dystrophic calcification generally following severe trauma leading to heterotopic ossifications of a single intramuscular connective tissue, MO pseudo-malignant, which is limited to soft tissue and is not associated to any trauma, and a MO associated with paraplegia, closed head injury or severe trauma (non-hereditary heterotopic ossification). 7,9 POH is characterized by progressive ossification of cutaneous, subcutaneous, and deep connective tissues and caused by an inactivation of GNAS in most cases.…”

Genetic abnormalities in Fibrodysplasia Ossificans Progressiva

“…Extra-skeletal bone formation associated with inflammation preceding the osseous conversion usually begins in the first decade, predominantly in the head, neck, and shoulders (Kartal-Kaess et al, 2010). Although the general phenotype of FOP, including the presence of congenital malformations of the great toes, is constant among individuals, there is wide variation in the severity of the disorder .…”