Aicardi syndrome is a rare severe developmental disorder. It results from an X-linked genetic defect that is fatal in males and, therefore, only manifests in females (except for rare 47, XXY cases).

Terminology

Aicardi syndrome is distinct from Aicardi-Goutieres syndrome, although both are named after Jean Aicardi (see below). 

Epidemiology

Due to its rarity, epidemiological data is limited. However, its incidence has been postulated at ~1/100000, with a prevalence of over 850 cases in the US and 4,000 globally. No ethnicity bias has been found ⁵.

Diagnosis

Aicardi syndrome is diagnosed clinically, supported by neuroimaging and EEG findings and sometimes genetic studies. The classic triad must be present ⁶:

1. agenesis of the corpus callosum

2. chorioretinal lacunae

3. infantile spasms or early-onset epilepsy

Neuroimaging features (see below) and EEG findings are supportive. In some cases speficic mutation may be identified, however, there is no single confirmatory test, and most cases arise from de novo mutations.

Clinical presentation

The typical presentation in infancy is with a triad of:

• infantile spasms: salaam seizures with typical bowing of the head

• corpus callosal dysgenesis: most consistent feature

• distinctive chorioretinal lacunae: essentially pathognomonic

Pathology

Although in some instances mutations in specific genes on the X chromosome have been identified (e.g. TEAD1 and OCEL1) these are heterogeneous ⁷.

Radiographic features

Characteristic malformations affect the brain, spine and eyes and include:

• brain

  • agenesis of the corpus callosum

  • colpocephaly

  • grey matter heterotopia

  • asymmetry of cerebral hemispheres

  • posterior fossa abnormalities (95%), including Dandy-Walker continuum:

    • posterior fossa cyst

    • cerebellar hypoplasia

    • tectal enlargement

  • choroid plexus papilloma

  • choroid plexus carcinoma

  • polymicrogyria (predominantly frontal and perisylvian)

  • intracranial cysts (diameters range between 1.0-5.0 cm)

    • midline interhemispheric: 81%

    • intraventricular: 29%

    • parenchymal: 10%

    • extra-axial: 8%

• ocular

  • microphthalmia

  • coloboma

• spine and ribs

  • scoliosis: 1/3 cases ⁵

  • spina bifida

  • butterfly or block vertebrae

  • hemivertebrae

  • abnormal costovertebral articulations

  • missing ribs ⁵

History and etymology

First described in 1961 by Jean Francois Marie Aicardi (1926-2015), a French neuropaediatrician ².