Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States.
Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States.
Bone. 2018 Apr;109:104-110. doi: 10.1016/j.bone.2017.10.009. Epub 2017 Oct 13.
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder in which heterotopic bone forms in the soft tissues. This often occurs in response to injury or inflammation, leading to joint immobilization and significant disability. There are currently no definitive treatment options for this devastating disease. Although the most dramatic phenotype in FOP is the episodic and progressive heterotopic ossification, patients report a number of symptoms that affect other organ systems. Post-mortem examination of FOP patients may contribute to our understanding of the underlying pathophysiology and complications of this disease. Here, we present the autopsy findings from three patients with FOP.
Autopsy findings in two of the three patients confirmed that the cause of death was cardiorespiratory failure in the setting of severe thoracic insufficiency from heterotopic ossification. Both of these patients also had evidence of right ventricular dilatation likely secondary to thoracic insufficiency. The third patient died from complications of a traumatic head injury after a fall but also had post-mortem evidence of thoracic insufficiency syndrome. All three patients had extensive, widespread heterotopic ossification and joint deformities consistent with FOP. There was extensive ossification of the spinal ligament in these patients, which may contribute to cervical spine rigidity. One patient was diagnosed post-mortem with a brainstem malformation. No additional significant abnormalities were noted in the other organ systems. Finally, we also demonstrate that cadaveric skin fibroblasts can be isolated for use as a potential source for future in vitro cell culture studies.
This autopsy case series provides valuable information about the underlying complications of FOP and contributes significantly to our knowledge of this rare yet debilitating disorder. Thoracic insufficiency syndrome, right heart dysfunction, widespread heterotopic ossification, spinal ligament ossification, and CNS malformations were clearly evident; however, most other non-bone tissues appeared to be spared from gross malformations. Finally, the ability to isolate live cells from cadaveric skin is an important technique that will facilitate future studies, particularly as induced pluripotent stem cells and other cell-based technologies evolve. This case series highlights the importance of post-mortem examinations and their contribution to our current knowledge of disease pathophysiology and comorbidities.
成骨不全性骨纤维发育异常（FOP）是一种超罕见的遗传性疾病，其软组织中会异位形成骨。这种情况通常是在受伤或炎症后发生，导致关节固定和严重残疾。目前，这种破坏性疾病还没有明确的治疗选择。尽管 FOP 最显著的表型是间歇性和进行性异位骨化，但患者还报告了许多影响其他器官系统的症状。对 FOP 患者进行尸检可能有助于我们了解这种疾病的潜在病理生理学和并发症。在这里，我们介绍了 3 例 FOP 患者的尸检结果。
在这 3 例患者中的 2 例，尸检结果证实死亡原因是心肺衰竭，同时伴有严重的胸壁发育不全导致的异位骨化。这两个患者均有右心室扩张的证据，可能是由胸壁发育不全引起的。第三个患者死于外伤导致的头部损伤并发症，但也有胸壁发育不全综合征的尸检证据。所有 3 例患者均有广泛的异位骨化和关节畸形，符合 FOP 的表现。这些患者的脊柱韧带广泛骨化，可能导致颈椎僵硬。一名患者死后被诊断为脑干畸形。其他器官系统未发现其他显著异常。最后，我们还证明可以从尸体皮肤中分离出成纤维细胞，作为未来体外细胞培养研究的潜在来源。
本尸检病例系列提供了有关 FOP 潜在并发症的宝贵信息，并极大地丰富了我们对这种罕见但使人衰弱的疾病的认识。明显存在胸壁发育不全综合征、右心功能障碍、广泛的异位骨化、脊柱韧带骨化和中枢神经系统畸形；然而，大多数其他非骨骼组织似乎没有明显的畸形。最后，从尸体皮肤中分离出活细胞的能力是一项重要的技术，它将促进未来的研究，特别是随着诱导多能干细胞和其他基于细胞的技术的发展。本病例系列强调了尸检的重要性，以及其对我们目前对疾病病理生理学和合并症的认识的贡献。
