Aicardi Syndrome
- Author: Ronald G Davis, MD, MPH, FAAP; Chief Editor: Bruce Buehler, MD
Background
In 1965, a French neurologist, Dr Jean Dennis Aicardi, described 8 children with infantile spasm-in-flexion, total or partial agenesis of the corpus callosum, and variable ocular abnormalities.[1] This clinical scenario, already reported in 1949, was recognized as an entity distinct from congenital infections. An additional 7 patients were described in 1969, and, in 1972, Dennis and Bower established the Aicardi syndrome designation.[2]
Further patient study demonstrated other less consistent characteristics outside the classic triad of findings. These additional characteristics include abnormal facies, cleft lip and palate, vertebral body abnormalities, and abnormalities of neuronal migration.[3] Most children have a moderate-to-severe degree of mental retardation, although less severely affected children occasionally are described. To date, only 2 affected children have been male, both with the XXY karyotype.
Pathophysiology
At present, no etiology explains all the manifestations of Aicardi syndrome. Findings are ascribed to neural tube overdistension during embryogenesis at 4-8 weeks' gestation, but experimental evidence is lacking, and the cause remains unknown.
Epidemiology
Frequency
International
Although cases occur throughout the world, exact incidence and prevalence is unknown. In a series of children with infantile spasm, 2% had Aicardi syndrome. Given the phenotypic heterogeneity and diagnostic difficulties associated with young children, Aicardi syndrome may be a more frequent cause of mental retardation and seizure in girls than previously thought. Some children may, in fact, have normal neurodevelopment, which significantly increases the potential numbers of children with Aicardi syndrome.[4]
Mortality/Morbidity
Aicardi syndrome is often complicated by severe mental retardation, intractable epilepsy, and a resultant propensity to pulmonary complications. The condition often leads to death in the first decade. Sudden, unexplained death is common.
Race
The syndrome occurs in people of diverse racial backgrounds throughout the world with no noted racial predominance.
Sex
Aicardi syndrome is thought to be an X-linked dominant disorder lethal to males. Except for 2 male children, all reported instances have been in females. Both males had XXY genotypes, which further supports an X-linked male lethal genetic substrate. This mutation appears to be de novo.[5, 6]
Age
Because Aicardi is a congenital syndrome, it is often first recognized during the neonatal period and infancy. Less severely affected individuals may live into childhood and adolescence, and diagnosis may be delayed. In one group of patients, diagnosis was delayed from 11-234 weeks after the onset of seizures.
