Multicenter study of mortality in achondroplasia

Area of Science:

• Medical Genetics
• Skeletal Dysplasias
• Public Health

Background:

• Achondroplasia is associated with increased mortality, particularly from brainstem compression in children and cardiovascular issues in adults.
• While clinical management has improved survival rates, achondroplasia patients still face higher mortality compared to the general population.

Purpose of the Study:

• To evaluate the mortality rates and causes of death in patients with achondroplasia receiving clinical care since 1986.
• To identify trends in mortality causes over the past three decades.

Main Methods:

• A multicenter, clinic-based study involving 855 achondroplasia patients assessed in four skeletal dysplasia clinics.
• Mortality data was cross-referenced with the National Death Index to determine vital status and causes of death.
• Standardized mortality rates (SMR) were calculated using U.S. population data from 1975, 1995, and 2000.

Main Results:

• A total of 12 deaths were recorded across 12,117 person-years, with the highest age-adjusted SMR observed in the 1-4 year age group.
• Cerebrovascular/cardiovascular events accounted for three of five deaths in the 1-4 year group; accidental events, including motor vehicle accidents, comprised half of deaths in the 5-24 year age group.
• While childhood mortality has decreased, this improvement lags behind that of the general population.

Conclusions:

• Causes of death in achondroplasia have shifted, with a decline in sudden deaths, pneumonia, and hydrocephalus, offset by an increase in cardiovascular/cerebrovascular and accidental deaths.
• Clinicians must recognize the elevated risk of accidental deaths, particularly vehicular accidents, and provide appropriate counseling to patients.
• Despite survival improvements, achondroplasia patients continue to experience higher mortality, underscoring the need for ongoing monitoring and management strategies.