Aicardi Syndrome

Updated: Mar 31, 2016
  • Author: Ravi Sunderkrishnan, MD; Chief Editor: Maria Descartes, MD  more...
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Overview

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.

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Pathophysiology

At present, no exact 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.

It has been hypothesized that spontaneous mutation occurs at the Xp22 chromosome. Attempts to pinpoint the exact chromosomal abnormality are ongoing in clinical trials. [4]

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Epidemiology

Frequency

United States

The estimated incidence in the United States in 1 in 105,000 live births. [5]

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. A study by Lund et al found the age-adjusted prevalence of Aicardi syndrome in Norway to be 0.63 cases per 100,000 females, as calculated for January 1, 2011. [6]

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, however, have normal neurodevelopment, which significantly increases the potential numbers of children with Aicardi syndrome. [7]

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.

The estimated average age of death is 8.8 years (range, 1 mo to 33 y). On the basis of the severity of the disease, the chances of surviving until age 27 years is estimated to be 62%. [5] The oldest individual reported in a paper was 32 years old. [8]

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. [9, 10]

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.

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