Disease Site

Aicardi syndrome, a disease that occurs exclusively in girls, is a rare genetic disorder characterised by the partial or complete absence of the corpus callosum. The corpus callosum, which connects the left and right cerebral hemispheres, is the junction where most of the communication between regions in the different halves of the brain crossover. Onset generally begins between the ages of 3 and 5 months with infantile spasms. Common manifestations are seizures, mental retardation and lesions on the retina. It may also be associated with other brain defects (e.g. microcephaly).2

Incidence

Aicardi syndrome occurs worldwide; the exact incidence and prevalence are unknown. It is estimated that 2 per cent of children who have infantile spasm have Aicardi syndrome.5 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.
All reported cases of Aicardi syndrome have been in females. It is thought to be an X-linked disorder lethal to males. This congenital disorder is commonly diagnosed in the neonatal period and infancy, with 3 to 5 months being the common ages of onset.6

Predisposing Factors

The cause of Aicardi syndrome is still unknown, but is presumed to be a genetic disorder carried on the X-chromosome in some cases, whilst being a random, sporadic mutation in others. Events early in utero, such as exposure to toxins, hypoxia and infections, have been suggested as possible causes; however, there is no conclusive evidence to support this.

Natural History

Complications of Aicardi syndrome include intractable epilepsy, cardiopulmonary dysfunction with an increased risk of infections, and choroid plexus papillomas which may cause obstructive hydrocephalus. Certain malignancies, such as embryonic soft tissue carcinoma, hepatoblastoma, and angiosarcoma occur more frequently in patients with this condition.

Clinical History

  • Aicardi syndrome is often diagnosed in infants who have presented with seizures, abnormal facial features or abnormalities on eye examination;1,3
  • Infantile spasms or fits (fits in those less than one year old) are the most common initial complaint. Other seizure types associated with Aicardi syndrome are hemiconvulsions, complex partial seizures, and focal motor seizures;1,3
  • Most affected children have mental retardation that is moderate to severe. The pattern of growth delay is across all areas of development, including speech, walking, social interaction etc;1,3
  • Most of these children are unable to move and are bedbound;1,3
  • Children with Aicardi syndrome typically lack even basic abilities to interact with their environments;1,3
  • Abnormalities in the eyes limit visual ability, causing blindness in most children.1,3

Clinical Examination

Findings on examination:

  • Overall developmental delay;
  • Inability to walk and speak – only 21% of patients can walk and 29% can communicate;
  • Abnormal features of the skull and face including an abnormally small head, asymmetrical facial features, cleft lip and palate can occur frequently;
  • Abnormalities of the backbone and the ribs may be present and scoliosis (sideways curvature of the backbone) resulting from these deformities can be disfiguring and disabling;
  • Decreased tone, involuntary muscle tightness and stiffness, or paralysis of one side of the body may also be present;
  • Ocular (eye) abnormalities such as decreased visual acuity, cataracts and retinal problems can occur.

General Investigation

Extensive lab workups are not usually indicated if the clinical picture is convincing. Investigations which may be considered include:

  • Genetic studies: High resolution karyotyping for affected children;
  • Imaging:
    • MRI can be used to assess the extent of CNS dysgenesis and exclude other causes of infantile seizures.
    • CT scan may show calcifications which would be more suggestive of an infective cause.
  • EEG: Abnormalities are often seen. The presence of a burst suppression pattern arising independently from each hemisphere is highly suggestive of Aicardi syndrome.
  • Ophthalmologic examination is essential, and may reveal classical features of optical malformation, including: microphthalmia, retrobulbar cyst, cataract, coloboma, retinal detachment and iris synechiae.

Prognosis

Prognosis varies depending upon the affected child’s overall health and severity of symptoms. Nearly all have moderate to severe learning difficulties and most are unable to communicate or walk; however, there are some children who are less severely affected. Children with Aicardi syndrome will generally require continuous care and commonly die within the first decade of life, although some have lived into the third decade.

References

  1. Abe K, Mitsudome A, Ogata H, et al. A case of Aicardi syndrome with moderate psychomotor retardation [in Japanese]. No To Hattatsu. 1990;22(4):376-80. [Abstract]
  2. Aicardi J, Lefebvre J, Lerique-Koechlin A. A new syndrome: Spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol. 1965;19(6):609-10.
  3. Carney SH, Brodsky MC, Good WV, et al. Aicardi syndrome: More than meets the eye. Surv Ophthalmol. 1993;37(6):419-24. [Abstract]
  4. Chevrie J, Aicardi J. The Aicardi syndrome. In: Pedley T, Meldrum B (eds). Recent Advances in Epilepsy. Edinburgh: Churchill Livingstone; 1986: 189-210. [Book]
  5. DiFazio MP, Davis RG. Aicardi syndrome [online]. Omaha, NE: eMedicine; 2005 [cited 28 December 2005]. Available from: URL link
  6. NINDS Aicardi syndrome information page [online]. Bethesda, MD: National Institute of Neurological Disorders and Stroke; 2005 [cited 28 December 2005]. Available from: URL link