Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva.
BACKGROUND
Fibrodysplasia ossificans progressiva, a rare genetic disorder of progressive extraskeletal ossification, is the most disabling form of heterotopic ossification in humans. However, little is known about the lifespan or causes of mortality in these patients. We undertook this study to determine the lifespan and causes of mortality in individuals who had fibrodysplasia ossificans progressiva.


METHODS
We reviewed comprehensive mortality reports from two large registries of patients with fibrodysplasia ossificans progressiva. Together, these registries comprise >90% of all known patients with this condition in the world. We noted the sex, dates of birth and death, and the cause of death for each individual. We verified the cause of death with extensive medical records, when available. We also collected date of birth, current age, and sex information for each living patient member of the International Fibrodysplasia Ossificans Progressiva Association.


RESULTS
Sixty deaths (thirty male and thirty female patients) were reported in the fibrodysplasia ossificans progressiva community during a thirty-three-year-period. For all sixty patients, the median age at the time of death was forty years (range, three to seventy-seven years). Data were sufficient to establish the cause of death in forty-eight (80%) of the sixty individuals. The median age at the time of death for the forty-eight patients (twenty-four male and twenty-four female patients) with an established cause of death was also forty years. The median lifespan estimated from the 371 individuals in the international fibrodysplasia ossificans progressiva community who were alive and the sixty who had died was fifty-six years (95% confidence interval, fifty-one to sixty years). The most common causes of death in patients with fibrodysplasia ossificans progressiva were cardiorespiratory failure from thoracic insufficiency syndrome (54%; median age, forty-two years) and pneumonia (15%; median age, forty years).


CONCLUSIONS
Fibrodysplasia ossificans progressiva is not only an extremely disabling disease but also a condition of considerably shortened lifespan. The most common cause of death in patients with fibrodysplasia ossificans progressiva is cardiorespiratory failure from thoracic insufficiency syndrome.
Kaplan
Frederick S
FS
Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Silverstein-2, 3400 Spruce Street, Philadelphia, PA 19104, USA. Frederick.Kaplan@uphs.upenn.edu
Zasloff
Michael A
MA
Kitterman
Joseph A
JA
Shore
Eileen M
EM
Hong
Charles C
CC
Rocke
David M
DM
D000293:Adolescent; D000328:Adult; D000368:Aged; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D006333:Heart Failure / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009221:Myositis Ossificans / Q000401:mortality*; D011014:Pneumonia / Q000401:mortality; D012042:Registries; D015996:Survival Rate