Skeletal dysplasia

Gene: ACVR1

Green List (high evidence)

Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.

Clinical trial with palovarotene.

Note variants in this gene are also associated with congenital heart disease, PMID 29089047.

Created: 29 Nov 2021, 5:52 a.m. | Last Modified: 23 Sep 2022, 8:15 a.m.

Panel Version: 0.209

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Fibrodysplasia ossificans progressiva, MIM# 135100; Congenital heart disease

Publications

• 16642017
• 29089047

Green List (high evidence)

Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments.

PMID: 19085907; 112 FOP (classic and atypical) cases (104 sporadic and 8 families) with R206H has the recurrent variant and a greater clinical variability seen in non-R206H patients (PMID: 26776312)

PMID: 18684712, 23572558, 20463014; functional studies demonstrating GoF

Created: 1 Jul 2020, 6:18 a.m. | Last Modified: 1 Jul 2020, 6:18 a.m.

Panel Version: 0.34

Phenotypes
Fibrodysplasia ossificans progressiva (MIM# 135100)

Publications

• PMID: 30071989
• 19085907
• 26776312
• 18684712
• 23572558
• 20463014