Details of Disease

General Information of Disease (ID: DISAT6WU)

Disease Name	Fibrodysplasia ossificans progressiva
Synonyms	myositis ossificans progressiva; fop; fibrodysplasia ossificans progressiva; progressive ossifying myositis; Stone Man syndrome; progressive myositis ossificans; Stone man syndrome
Disease Class	FB31: Muscle calcification/ossification
Definition	Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites.
Disease Hierarchy	DISYKSRF: Genetic disease DIS5HJ01: Subcutaneous tissue disorder DIS5PU87: Skeletal system disorder DISAT6WU: Fibrodysplasia ossificans progressiva
ICD Code	ICD-11 ICD-11: FB31.1 ICD-10 ICD-10: M61.1 Expand ICD-11 'FB31.1 Expand ICD-10 'M61.1
Disease Identifiers	MONDO ID MONDO_0007606 MESH ID D009221 UMLS CUI C0016037 OMIM ID 135100 MedGen ID 4698 Orphanet ID 337 SNOMED CT ID 82725007

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Palovarotene	DMAD2OZ	Approved	Small molecular drug	[1]
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This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Garetosmab	DMFFIDA	Phase 3	Antibody	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SMAD1	TT9GR53	moderate	Biomarker	[3]
ASPA	TT6TLZP	Strong	Biomarker	[4]
FKBP1A	TTMW94E	Strong	Altered Expression	[5]
RARG	TT1Q3IE	Strong	Biomarker	[6]
ACVR1	TTJNBQA	Definitive	Autosomal dominant	[7]
ACVR1	TTJNBQA	Definitive	Biomarker	[8]
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⏷ Show the Full List of 6 DTT(s)

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NOG	OTGRHHPG	Limited	Genetic Variation	[9]
CHTOP	OTMMNZ65	moderate	Biomarker	[10]
A1CF	OTJBKFA1	Strong	Biomarker	[4]
ASPM	OTKXQMNA	Strong	Biomarker	[4]
BMP5	OTC0Y6E0	Strong	Altered Expression	[11]
CHRD	OTNM60Y1	Strong	Altered Expression	[12]
GPC1	OTQKRSSV	Strong	Altered Expression	[13]
INTS3	OT7NX4CD	Strong	Genetic Variation	[14]
ROPN1L	OTRWZJ68	Strong	Biomarker	[4]
ACVR1	OT4JATFE	Definitive	Autosomal dominant	[7]
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⏷ Show the Full List of 10 DOT(s)

References

1	FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 215559
2	ClinicalTrials.gov (NCT05394116) Phase 3 Randomized, Placebo-Controlled Study to Assess Safety, Tolerability, and Efficacy of Garetosmab in Patients With Fibrodysplasia Ossificans Progressiva. U.S.National Institutes of Health.
3	Activin A amplifies dysregulated BMP signaling and induces chondro-osseous differentiation of primary connective tissue progenitor cells in patients with fibrodysplasia ossificans progressiva (FOP).Bone. 2018 Apr;109:218-224. doi: 10.1016/j.bone.2017.11.014. Epub 2017 Nov 21.
4	Restoration of normal BMP signaling levels and osteogenic differentiation in FOP mesenchymal progenitor cells by mutant allele-specific targeting.Gene Ther. 2012 Jul;19(7):786-90. doi: 10.1038/gt.2011.152. Epub 2011 Oct 20.
5	The effect of Activin-A on periodontal ligament fibroblasts-mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva.J Cell Physiol. 2019 Jul;234(7):10238-10247. doi: 10.1002/jcp.27693. Epub 2018 Nov 11.
6	Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP).Bone. 2018 Apr;109:153-157. doi: 10.1016/j.bone.2017.09.016. Epub 2017 Sep 28.
7	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
8	Analysis of clinical manifestations and treatment in 26 children with fibrodysplasia ossificans progressiva in China.World J Pediatr. 2020 Feb;16(1):82-88. doi: 10.1007/s12519-019-00302-x. Epub 2019 Sep 16.
9	Functional analysis of alleged NOGGIN mutation G92E disproves its pathogenic relevance.PLoS One. 2012;7(4):e35062. doi: 10.1371/journal.pone.0035062. Epub 2012 Apr 18.
10	Animal models of fibrodysplasia ossificans progressiva.Dev Dyn. 2018 Feb;247(2):279-288. doi: 10.1002/dvdy.24606. Epub 2017 Dec 1.
11	Over-expression of BMP4 and BMP5 in a child with axial skeletal malformations and heterotopic ossification: a new syndrome.Am J Med Genet A. 2007 Apr 1;143A(7):699-706. doi: 10.1002/ajmg.a.31649.
12	Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesis.J Bone Joint Surg Am. 2003 Apr;85(4):667-74. doi: 10.2106/00004623-200304000-00013.
13	HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells.J Cell Biochem. 2007 Dec 15;102(6):1493-503. doi: 10.1002/jcb.21370.
14	Identification of submicroscopic genetic changes and precise breakpoint mapping in myelofibrosis using high resolution mate-pair sequencing.Am J Hematol. 2013 Sep;88(9):741-6. doi: 10.1002/ajh.23495. Epub 2013 Aug 1.