A Three-Generation Pedigree of Multifocal Heterotopic Ossification With Bilateral Involvement.

Abstract

Heterotopic ossification (HO) can be classified as nonhereditary HO (NHHO) or hereditary HO (HHO). Hereditary HO includes 2 different forms: fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH). Each of these disorders is caused by mutations in a single (different) gene. Clinical diagnosis of FOP can be confirmed by sequence analysis of the ACVR1 gene. Fewer than 10 families with autosomal dominant inheritance of FOP have been reported. The authors report clinical manifestations, pedigree analysis, and mutational analysis of the ACVR1 in a 3-generation Chinese family with 4 individuals presenting multifocal and bilateral involvement of HO. Clinical features of affected individuals of the family were not consistent with the classic FOP or atypical FOP. Exon sequencing was performed on every family member and 3 sporadic NHHO patients who did not belong to this family. All family members and 3 sporadic NHHO patients carried 2 hereditary homozygous silent mutations- c.270C>T and c.690G>A-the new and unique mutations in ACVR1. These results may suggest that the affected individuals in this family present a novel FOP-variant syndrome or a new form of HHO. To the authors' knowledge, this is the first well-documented instance of a 3-generation Chinese family with multifocal and bilateral involvement of HO. [Orthopedics. 2021;44(1):e139-e145.].