Aicardi Syndrome

Updated: Apr 27, 2023
  • Author: Ravi Sunderkrishnan, MD; Chief Editor: Maria Descartes, MD  more...
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Practice Essentials

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.

Signs and symptoms of Aicardi syndrome


Neurodevelopmental characteristics can include the following:

  • Microcephaly
  • Axial hypotonia
  • Appendicular hypertonia with spasticity that often affects one side
  • Brisk deep tendon reflexes
  • Hemiparesis

Moderate to severe global developmental delay and intellectual disability are expected, but individuals with only mild or no learning disabilities or developmental delay have been reported.

Infantile spasms, seizures, or epilepsy develop before age 3 months.


Pathognomonic lesions called chorioretinal lacunae commonly cluster around the optic disc of the eye and are described as punched-out, white or yellow defects.


Craniofacial characteristics can include the following:

  • Microcephaly
  • Hemifacial asymmetry
  • Microphthalmia
  • Plagiocephaly
  • Short philtrum
  • Cleft lip and palate


Gastrointestinal characteristics can include the following [4] :

  • Constipation
  • Gastroesophageal reflux
  • Diarrhea
  • Feeding difficulties


Small hands, along with an increased incidence of hand malformations, have been reported.


Costovertebral abnormalities, such as hemivertebrae, fused or butterfly vertebrae, and rib abnormalities, may be present. Scoliosis resulting from these deformities can be disfiguring and disabling.

Workup in Aicardi syndrome

Imaging studies

Neuroimaging can delineate the degree of central nervous system (CNS) dysgenesis and help to evaluate other potential etiologies of intractable epilepsy and developmental delay. [5]

Magnetic resonance imaging (MRI) is preferred because its anatomic resolution is superior to computed tomography (CT) scanning.

Ophthalmologic assessment

Evaluation by an experienced ophthalmologist is crucial, especially if optic malformation (eg, anterior chamber abnormalities) makes the examination more difficult.

Electroencephalography (EEG)

A pattern highly suggestive of the diagnosis in the typical clinical context is the presence of a burst suppression pattern, with complete asynchrony between the two hemispheres.

Management of Aicardi syndrome

Management includes the following:

  • Seizures - Seizures are treated with multiple antiepileptic medications; their effectiveness varies with each patient
  • Spasticity - Patients may benefit from specialized care with physical medicine and rehabilitation specialists as well as physical, occupational, and speech therapists
  • Gastrointestinal issues and constipation - These can be managed under the care of a pediatrician or pediatric gastroenterologist

Palliative epilepsy surgery in the form of corpus callosectomy of a partial corpus callosum and the use of vagal nerve stimulation have been reported to be of variable benefit. [6]



At present, no exact etiology explains all the manifestations of Aicardi syndrome. It has been hypothesized that spontaneous mutation occurs at the Xp22 chromosome. Attempts to pinpoint the exact chromosomal abnormality are ongoing in clinical trials. [7]  

The identification of recurrent hypomethylation in the KCNAB3 gene's promoter and 5' areas in patients with Aicardi syndrome, as discussed in a study by Piras et al, may aid in the understanding of neuronal hyperactivity, as well as the neurodevelopmental and/or neuroinflammation pathways, in these individuals. [8]




United States

The estimated incidence in the United States in 1 in 105,000 live births. [9]


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. [10]

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. [9]


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%. [9] The oldest individual reported in a paper was 32 years old. [4]


The syndrome occurs in people of diverse racial backgrounds throughout the world with no noted racial predominance.


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. [11, 12]


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.