OBJECTIVE: 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.
FINDINGS: 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.
CONCLUSIONS: 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.