Table 3.

Genes of Interest in the Differential Diagnosis of Fibrodysplasia Ossificans Progressiva

Gene(s)DisorderMOIClinical Features of Differential Diagnosis Disorder
Overlapping w/FOPDistinguishing from FOP
EXT1
EXT2 		Hereditary multiple osteochondromas ADMultiple osteochondromas arising from growth plate in juxtaphyseal region of long bones or from surface of flat bones
  • No hallux malformations
  • No heterotopic ossification
GNAS Progressive osseous heteroplasia
(See Disorders of GNAS Inactivation.)		AD 1Extensive bone formation (episodic & cumulative) w/in soft connective tissues
  • No hallux malformations or inflammatory soft-tissue swellings
  • Individuals w/POH typically develop ossification w/in superficial dermal layer of the skin (which is unaffected in FOP.
  • Predominance of membranous rather than endochondral bone formation
PTPN11 Metachondromatosis
(OMIM 156250)		ADOsteochondromas & enchondromas
  • No hallux malformations
  • No heterotopic ossification
ROR2 Brachydactyly type B1
(OMIM 113000)		ADDistal limb (terminal) reduction-type defects w/brachydactylyNo heterotopic ossification

AD = autosomal dominant; FOP = fibrodysplasia ossificans progressiva; MOI = mode of inheritance; POH = progressive osseous heteroplasia

1.

Disorders of GNAS inactivation are inherited in an autosomal dominant manner, with the specific phenotype determined by the parental origin of the defective allele.

From: Fibrodysplasia Ossificans Progressiva

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2025.
Copyright © 1993-2025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2025 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.