Universität zu Köln

Seefried, L., Morhart, R. and Semler, O. (2018). Fibrodysplasia ossificans Progressive - FOP. Osteologie, 27 (4). S. 215 - 222. STUTTGART: GEORG THIEME VERLAG KG. ISSN 2567-5818

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Abstract

Fibrodysplasia ossificans progressiva (FOP) is caused by an activating mutation in the Activin-Rezeptor 1 (ACVR1 / ALK2) Gene on Chromosome 2q23-24. Associated increased activity of the receptor predisposes to the development of heterotopic ossifications in the connective tissue, particularly in the muscles. The prevalence of the disorder is estimated to range between 1 in 1-2 Mio persons. At the time of birth, the only hallmark of the disease is a characteristic malformation of the great toe. During childhood, affected patients episodically develop painful soft tissue reactions, so-called flare-ups, marked by inflammation and swelling upon minor trauma. Subsequently these lesions form bone structures within the soft tissues by means of endochondral ossification. Typically, first lesions occur in the proximal, cranial, dorsal regions of the body, i. e. around the shoulder and the neck. Ossifications are irreversible and accumulate over time in the soft tissues, thereby progressively limiting patients' mobility. Increasing limitations of chest expansion eventually compromise respiratory capacity, promote the risk for pneumonia and right-sided heart failure. Therapeutic approaches focus on preventing additional trauma and interventions that might trigger additional heterotopic ossification, including avoidance of iatrogenic interventions like operations, biopsies and intramuscular injections. Supportive care comprises psychologic counseling, provision with appropriate technical tools as well as analgesic treatment, preferentially using NSAIDs. In case of a trauma, short term treatment with high doses of glucocorticoids is recommended in order to reduce the risk and extension of flare-ups and subsequent ossifications. Currently various novel therapeutic approaches are being evaluated. Among these, the retinoic acid receptor gamma (RARg) agonist Palovarotene is most advance in development. By binding to RARg, Palovarotene directly targets and interferes with the ALK2 induced signaling cascade considered a central aspect of the pathomechanism of the disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seefried, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Morhart, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Semler, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-164682
Journal or Publication Title:	Osteologie
Volume:	27
Number:	4
Page Range:	S. 215 - 222
Date:	2018
Publisher:	GEORG THIEME VERLAG KG
Place of Publication:	STUTTGART
ISSN:	2567-5818
Language:	German
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Orthopedics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16468