Abstracts

Rationale: Aicardi syndrome (AIC) is a rare neurological disorder defined by agenesis of the corpus callosum, chorioretinal lacunae and infantile spasms. Other characteristic features include brain, eye and skeletal abnormalities. The world prevalence is 300-500. The oldest median survival is 18 years. The incidence is unknown. We sought to revise the prevalence, determine the life expectancy, and estimate the incidence of AIC in the United States.Methods: 396 subjects with known or suspected AIC was compiled from multiple sources including family support groups. Presence of AIC was by parental report of a physician's diagnosis or documentation of diagnostic criteria from a survey. It is unlikely that all recently diagnosed cases from the US were identified. Incidence and prevalence were calculated for ascertainments rates of 50%, 65% and 80% for cases born in 2001-2005. Survival analysis was by Kaplan-Meir methods for all US cases. US cases were considered a representative sample of all AIC because of structured support systems and frequent follow-up among AIC families. The hazard rate was the rate of death among survivors at each age. US prevalence for cases age 0-25 years was calculated from the estimated annual incidence and corresponding annual survival rates.Results: Parental report of AIC was confirmed in 97% of a sample completing a survey. 91% met the criteria based on the classic triad for AIC. Six cases did not have chorioretinal lacunae but had other typical features. The total cohort of 396 represented 28 countries, 43 US States, and the District of Columbia. 81% were from English-speaking countries, including the US (n=268), Canada (n=20), the UK (n=25) and other (n=6). Mean last known age was 8.9 years (median 7.3, range <1 month to 42 years). 43 cases were deceased with mean age at death of 8.4 years (median 7.8, range 1 month to 25 years). 270 cases were alive on January 1, 2006, 27 at least 20 years of age. Of 268 US cases, including 33 deceased, the probability of survival at 25 years was 0.61 (95% CI 0.45-0.77) (Fig 1). The risk of death dropped after the first year of life until age 4 (Fig 2). After age 4, there was a continuous increase in risk until it peaked at age 16. Risk of death dropped significantly after age 16. Life expectancies by 5-year increments were 95% (age 5-10), 86% (age 10-15), 87% (age 15-20) and 91% (age 20-25). 94 US cases were born in 2001-2005 (mean 19 per year, range 16-22). Incidence per live births of AIC in the US based on ascertainment rates of 50%, 65% and 80% were 1:105,000, 1:138,000 and 1:167,000, respectively. Similarly, estimates for US prevalence were 806, 615 and 509.Conclusions: AIC is more common than previously reported. Over half of the cases survive to at least age 30. The risk of death by age follows other congenital disorders (e.g., cerebral palsy) with a wide range in severity of functional disability. The longer life expectancy in our study hint at a higher functioning capacity. Parents should be counseled that severe mental retardation and death in childhood are no longer prognostic indicators for AIC. (Source of funding was RTI International).