Aicardi Syndrome

What Causes Aicardi Syndrome?

Scientists believe that an abnormal mutation in a specific gene (or multiple genes) causes Aicardi Syndrome. However, the precise gene that causes the condition is still unknown. Researchers are nearly certain that the responsible gene is on the X chromosome because the syndrome almost always affects girls.

A child’s cells contain genetic material called chromosomes, and the genes that control the body’s development and function reside on those chromosomes. Each child inherits either an X or Y chromosome from each parent. Males have one X chromosome and one Y chromosome. Females have two X chromosomes.

Scientists think that the Aicardi Syndrome gene mutation occurs in a gene on the X chromosome. Because males have only one X chromosome and thus only one copy of the involved gene, the abnormal mutation is usually fatal early in fetal development. Most males with the mutation do not survive to birth.

However, females with the mutation on one X chromosome likely have a normal gene on the other X chromosome. This second normal gene may allow the fetus to survive and develop Aicardi Syndrome in infancy.

Is Aicardi Syndrome Hereditary?

Although the cause of Aicardi Syndrome is genetic, scientists do not believe that the condition is passed from parent to child. Women with the syndrome have not transmitted the syndrome to their children, and no cases of the syndrome running in families have been reported. This suggests that the triggering gene mutation happens spontaneously sometime after conception.

How Is Aicardi Syndrome Detected?

The earliest sign of Aicardi Syndrome is typically seizures that begin in infancy. The most common type of seizure is a single, whole-body jerk called an infantile spasm. The spasms may occur several times a day, and the baby is usually awake when they happen.

Infantile spasms in Aicardi Syndrome differ from the more common tonic-clonic type of seizure. In tonic-clonic episodes, the baby’s arms and legs usually jerk rhythmically, and it is common for the baby to lose consciousness during the seizure.

Babies with Aicardi Syndrome often stop having infantile spasms as they get older. Sometimes the spasms are replaced with tonic-clonic or other types of seizures.

Other common signs of Aicardi Syndrome include:

• Intellectual and motor developmental delays
• Atypically small head and/or eyes
• Significant muscle weakness
• Abnormalities in the retina or optic nerve that can be detected during eye exams
• Abnormal spinal or rib development

How Is Aicardi Syndrome Diagnosed?

Doctors can diagnose Aicardi Syndrome when a baby presents the key features of the disorder, including:

• Female sex
• Seizures, especially infantile spasms
• Lesions or holes in the retina or optic nerve
• Underdevelopment or absence of the corpus callosum

The diagnostic process usually includes several different exams to look for these features, including:

• Eye exam
• Electroencephalogram (EEG) to measure brain activity
• Imaging scans such as computerized tomography (CT) or magnetic resonance imaging (MRI) to look for abnormalities in brain structure

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Aicardi Syndrome Treated?

No treatment will cure Aicardi Syndrome. Most of the disorder’s symptoms, such as developmental disabilities and vision problems, will not improve with treatment. However, sometimes medicines will help control seizures. Doctors can prescribe various anti-seizure drugs to get the symptoms under control. Because individual patients respond differently to particular medications, the doctor may need to try more than one drug to find the one that works best.

How Does Aicardi Syndrome Progress?

The effects of Aicardi Syndrome vary widely depending on the severity of the disorder. In severe cases, seizures and secondary complications such as respiratory infections may be fatal in childhood. In less severe cases, symptoms may be milder. In all cases, intellectual disabilities are significant. Motor and vision impairments will also likely create the need for life-long care.

How Is Aicardi Syndrome Prevented?

There is no known way to prevent Aicardi Syndrome. Scientists have not identified any risk factors that appear to trigger the disorder-causing gene mutation. The precise mutation remains unknown, so there is, as yet, no way to know which babies will develop the syndrome.

Aicardi Syndrome Caregiver Tips

Coping with Aicardi Syndrome is difficult, but you can help your child live a better life by seeking knowledge and support.

• Educate yourself about the disorder. Little is known about the causes of Aicardi Syndrome, but the more you know about how the condition affects your child, the better you can support them.
• Find support from the AS community. The rarity of the syndrome may make you feel like you’re on your own, but you’re not. Online resources can connect you with other families living with AS.

Many people with Aicardi syndrome and seizure disorders also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with seizure disorders:

• Many people with seizure disorders also suffer from attention-deficit/hyperactivity disorder (ADHD) or learning disabilities.
• About a third of people with seizure disorders suffer from depression, and about a quarter suffer from anxiety.
• Autism spectrum disorder, Alzheimer’s disease, and other forms of dementia are more common in people with seizure disorders.

Aicardi Syndrome Brain Science

Scientists know very little about the cause of Aicardi Syndrome. The fact that the disorder only affects female babies strongly suggests that the genetic trigger involves the X chromosome, but the chromosome carries hundreds of individual genes. Research is focused on identifying which gene or genes are involved in the syndrome’s origin to develop effective treatments.

Some studies have focused on the relationship between Aicardi Syndrome and other disorders with similar symptoms, such as Dandy-Walker Syndrome. The hope is the connection between the disorders may lead researchers to a shared genetic cause.

Aicardi Syndrome Research

Title: Study of Selected X-Linked Disorders: Aicardi Syndrome

Stage: Recruiting

Principal Investigator: Ignatia B. Van den Veyver, MD 

Baylor College of Medicine

Houston, TX

Based on our current understanding of Aicardi syndrome, the condition is hypothesized to occur due to a genetic change on the X-chromosome. Our team is investigating Aicardi syndrome to identify the specific gene location associated with the disorder. We are collecting blood and skin biopsy samples from patients and their parents. A permanent cell line is prepared, and DNA from the blood and skin samples and cell lines is isolated and then used for genetic testing. Our current research includes microarray analysis which we are using to look for duplications or deletions of genetic material, mutation analysis of candidate genes by sequencing, reviewing medical records to identify trends suggesting possible candidate genes of interest, and X chromosome inactivation studies.

Title: Brain Development Research Program

Stage: Recruiting

Sub-investigator: Anne Slavotinek, MD 

University of California, San Francisco

San Francisco, CA

Dr. Elliott Sherr and his collaborators at the University of California, San Francisco (UCSF) are studying the genetic causes of disorders of cognition and epilepsy, in particular disorders of brain development that affect the corpus callosum, such as Aicardi syndrome, as well as two additional brain malformations, polymicrogyria and Dandy-Walker malformation. The investigators’ research aims to use a better understanding of the underlying genetic causes as a foundation to develop better treatments for these groups of patients.