Aicardi's Syndrome

This is a rare genetic condition characterised by:

• Complete or partial absence of the corpus callosum; this is the central part of the brain that connects the right and left sides.¹
• Chorioretinal lacunae
• Severe seizures

The outcome of Aicardi's syndrome is severe, with a high early mortality, considerable morbidity and a generally poor developmental outcome.²

Prevalence

There are probably between 300 and 500 cases worldwide. A recent survey of Swedish children found a prevalence rate in the range of 2-15 per 100,000 girls.³
It has been reported in just 1 of 2 homozygous twins;⁴ cases occur as spontaneous mutations - does not tend to run in families.

Pathogenesis

It affects girls almost exclusively. The few males that demonstrate the disease have Klinefelter's syndrome (47XXY).^5,6

The lesion has been gene mapped to the X chromosome with a suggested locus at Xp22.3⁷ (X linked dominant) and is lethal to the male fetus who has no second X chromosome, but females or those with Klinefelter's syndrome may survive on the basis of the normal other X chromosome.⁸

The disease is usually identified between 3 and 5 months old. Most will have had normal births and have seemed to be developing normally until having infantile spasms.
The known age range of affected children is from birth to the mid-20s. Median age of survival is 18.5 years.

• Epilepsy presents as flexion spasms.
• Chorioretinal lacunae (holes). The level of vision depends upon the extent of lacunae and the degree of mental impairment.
• Mental retardation.
• Microcephaly, enlarged ventricles; or porencephalic cysts (a gap in the brain where there should be healthy brain tissue)

There is agenesis of the corpus callosum in about 75% of cases and partial agenesis in the other 25%.⁹
Several other features have been described but they are not as constant as those mentioned above. Some are reported in isolated cases.

• Growth:
  Growth retardation. Growth rate slows at age 10 years to below the 5th percentile and weight gain slows at age 7 years to below the 25th percentile.¹⁰
• Face:
  Facial asymmetry, cleft lip and palate, prominent premaxilla, upturned nasal tip, decreased angle of the nasal bridge and sparse lateral eyebrows.
• Eyes:
  Microphthalmia (25%¹¹), optic nerve coloboma, bilateral chorioretinopathy, retinal detachment, cataract, nystagmus, optic atrophy.
• Skeletal:
  Absent, extra, fused or bifid ribs, malformed vertebrae, spina bifida, scoliosis, proximally placed thumbs, camptodactyly and hypoplasia of the fifth finger.
• Skin:
  Scalp lipoma, multiple naevi, skin tags, haemangiomas, giant melanotic naevus.
• Central nervous system:
  Hypotonia, Dandy-Walker malformation, enlarged lateral and third ventricles, Arnold-Chiari malformation, cavum septum pellucidum, choroid plexus cyst, delayed myelination, subependymal or cortical heterotopias, hypoplastic cerebellar vermis.
• Gastrointestinal dysfunction:
  Nausea, constipation.
• Endocrine:
  Precocious puberty.
• Associated malignancies:
  Hepatoblastoma, benign teratoma, embryonal carcinoma, metastatic angiosarcoma.

Psychological and behavioural problems

• Nearly all children with Aicardi syndrome have severe learning difficulties.
• Most have no expressive language and remain totally dependent. A few have some understanding of language, can walk with support or independently and are fairly responsive to the environment.
• Self-harm and aggression towards people and objects has been reported and may be involuntary.
• Disturbed sleep and waking in the night are common and possibly due to fitting.

• An EEG¹² may show the characteristic pattern of hypsarrhythmia - sometimes called West's syndrome.
• MRI scan or CT scan of head will help demonstrate the loss of neural tissue.

Antenatal diagnosis

Sometimes abnormalities of the brain are revealed at routine antenatal ultrasound scanning but this is a minority. There is no specific intrauterine test. As it does not run in families, there is usually no reason to suspect it until it appears.

There is no cure, patients are usually very dependent and may have behavioural problems.
Managing the epilepsy is important and can be very difficult.

Prognosis depends upon the severity of lesions, but life is usually very short with death in childhood.