Bone Biology Laboratory, School of Medicine, Rosario National University, Argentina; Reumatología y Enfermedades Óseas Rosario, Argentina; National Council of Scientific and Technical Research (CONICET), Argentina.
Department of Image, Sanatorio Británico, Rosario, Argentina.
Bone. 2022 Feb;155:116287. doi: 10.1016/j.bone.2021.116287. Epub 2021 Dec 8.
Heterotopic ossification (HO) is the formation of extraskeletal bone in muscle and soft tissues and could be genetic or non-genetic. The classic presentation of non-genetic HO is in young adults with a clear history of local trauma, surgery or prolonged immobilization after spinal cord and traumatic brain injuries. Genetic HO has a significant clinical severity compared to non-genetic causes and includes fibrodysplasia ossificans progressiva (FOP). FOP is an extremely rare genetic skeletal disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites affecting skeletal muscles, fascia, tendons, and ligaments. Previously, it has been reported an association between SARS-CoV-2 infection (COVID-19) and HO or FOP exacerbation with unclear etiopathogenesis. The possible mechanisms could be prolonged immobilization and systemic inflammation. Here, we describe the case of a 55-year-old apparently healthy man who suffered from a severe SARS-CoV-2 infection after that he experienced an extensive and progressive heterotopic ossification around the shoulders, the elbows, the hip, the knees, and the ankles. Because of the clinical severity, the painful soft-tissue swelling, the progressive HO, and the bilateral congenital hallux valgus deformity, a late-onset atypical FOP was suspected. Nevertheless, no variant of clinical significance has been identified in the coding regions and splicing sites in the ACVR1 gene and no deletions and/or duplications have been identified in exonic regions.
异位骨化(HO)是指在肌肉和软组织中形成的骨骼外骨骼,可分为遗传或非遗传。非遗传性 HO 的典型表现是在年轻成人中,有明确的局部创伤、脊髓和颅脑损伤后手术或长时间固定的病史。与非遗传性原因相比,遗传性 HO 的临床严重程度显著,包括纤维发育不良性骨化进展症(FOP)。FOP 是一种极其罕见的遗传性骨骼疾病,其特征为大脚趾先天性畸形和进行性异位骨化,在影响骨骼肌肉、筋膜、肌腱和韧带的特征性骨骼外部位形成质量正常的骨骼。先前有报道称 SARS-CoV-2 感染(COVID-19)与 HO 或 FOP 恶化之间存在关联,但发病机制尚不清楚。可能的机制可能是长时间的固定和全身炎症。在这里,我们描述了一例 55 岁的健康男性,他在感染严重的 SARS-CoV-2 后,出现了广泛而进行性的肩部、肘部、臀部、膝盖和脚踝周围异位骨化。由于临床严重程度、疼痛性软组织肿胀、进行性 HO 和双侧先天性大脚趾外翻畸形,怀疑为迟发性非典型 FOP。然而,在 ACVR1 基因的编码区域和剪接位点未发现具有临床意义的变异,也未在外显子区域发现缺失和/或重复。