Mortality in achondroplasia study: A 42‐year follow‐up

Abstract

Achondroplasia (ACH) is the most common dwarfing condition having a prevalence of 1/25,000 live births. An increase in overall mortality, age specific mortality up to age 34 years and heart disease-related mortality was first reported in a 1987 study of a large population of ACH individuals. Since this study, concern about premature death, particularly in young adults, has persisted in the ACH population. The present study was undertaken to follow-up the patterns of mortality in a more contemporaneous ACH population. The vital status of 718 ACH individuals from the original study and 75 new ACH individuals was determined through the search of two computerized mortality database. The results showed that the overall mortality and age-specific mortality at all ages remained significantly increased. Rates of death were similar across all 42 years of follow-up suggesting that higher death rates were still occurring in the contemporary ACH population. Accidental, neurological, and heart disease-related deaths were increased in adults. Heart disease-related mortality, between ages 25 and 35, was more than 10 times higher than the general population. Overall survival and the average life expectancy for this ACH population were decreased by 10 years. These results demonstrate that despite advances in the knowledge of the natural history of ACH and health care needs of this population, mortality remains significantly increased. The high rate of heart disease related deaths illustrates the need to identify risk factors in the ACH population and develop treatment interventions accordingly.

Neutral Endopeptidase-Resistant C-Type Natriuretic Peptide Variant Represents a New Therapeutic Approach for Treatment of Fibroblast Growth Factor Receptor 3–Related Dwarfism

“…ACH is associated with significant morbidity and increased mortality, and current treatments are mostly surgical (Trotter and Hall, 2005;Wynn et al, 2007). BMN 111, a CNP variant, offers a potential treatment for ACH that addresses the underlying biochemical defect.…”

“…Neurologic complications in infants due to foramen magnum stenosis and cervicomedullary compression may lead to potentially lethal hydrocephalus, hypotonia, respiratory insufficiency, apnea, cyanotic episodes, feeding problems, and quadriparesis. Mortality is increased in the first 4 years of life and in the fourth to fifth decades (Trotter and Hall, 2005;Wynn et al, 2007). Current treatments include neurosurgery and orthopedic interventions; limb lengthening to increase stature requires multiple operations over 2-3 years and remains controversial (Horton et al, 2007;Shirley and Ain, 2009).…”

Neurosurgical implications of achondroplasia

“…Only 1 shunt has been inserted in a child with achondroplasia in the past 20 years at The HSC. The practice of decompressive surgery for cervicomedullary compression, however, appears to be increasing with the recognition of the incidence of sudden death in children with achondroplasia, 33,40 a greater ability to document central apnea on sleep studies, and good-quality MR imaging of this region on which stenosis and spinal cord signal change can be identified. There are many unique features to consider when contemplating surgery in the child with achondroplasia, and these need to be assessed to minimize unnecessary procedures and operative morbidity.…”

Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height

“…Data from a recent 40-y morbidity and mortality study show that cardiovascular disease-related deaths in achondroplasia are higher than expected compared with age-and sex-matched individuals of average stature, which suggests an influence of central adiposity (6).…”