Clinical-pathological correlations in three patients with fibrodysplasia ossificans progressiva.

Autor: Wentworth KL; Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States. Electronic address: Kelly.wentworth@ucsf.edu., Bigay K; Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States., Chan TV; Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States., Ho JP; Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States., Morales BM; Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States., Connor J; Division of Pathology, University of Wisconsin, Madison, WI, United States., Brooks E; Division of Pathology, University of Wisconsin, Madison, WI, United States., Shahriar Salamat M; Division of Pathology, University of Wisconsin, Madison, WI, United States., Sanchez HC; Division of Pathology, University of California, San Francisco, CA, United States., Wool G; Department of Pathology, University of Chicago, Chicago, IL, United States., Pignolo RJ; Department of Medicine, Mayo Clinic, Rochester, MN, United States., Kaplan FS; Departments of Orthopaedic Surgery and Medicine, Center for Research in FOP and Related Disorders at the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, United States., Hsiao EC; Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States. Electronic address: Edward.Hsiao@ucsf.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2018 Apr; Vol. 109, pp. 104-110. Date of Electronic Publication: 2017 Oct 13.
DOI: 10.1016/j.bone.2017.10.009
Abstrakt: 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.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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