Aicardi syndrome

Aicardi syndrome usually occurs sporadically or randomly due to new mutations that occur naturally in a person. Because of this, it is unlikely that other members of the family would also have Aicardi syndrome. However, if other people in your family have symptoms that are consistent to those of Aicardi syndrome, they should be evaluated by a medical geneticist. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website.

Aicardi syndrome was first recognized as a distinct syndrome in 1965 by a French neurologist by the name of Jean Aicardi.

The common abbreviation for Aicardi syndrome is AIC

The average life expectancy for someone with Aicardi syndrome can vary based on severity with the mean age of death at 8.3 years and the median age of death at 18.5 years. Those who are more mildly affected have been recorded to live into their late 40s.

Aicardi syndrome is a genetic condition that occurs almost exclusively in females. Most commonly, those with Aicardi syndrome have a missing or an underdeveloped corpus callosum, the tissue that separates the left and right sides of the brain. An underdeveloped or missing corpus callosum can cause infantile spasms which are seizures that happen during the first few months of life and intellectual disabilities. Affected individuals also have chorioretinal lacunae, which are defects in the light-sensitive tissue at the back of the eye (retina).

Aicardi syndrome causes seizures in infancy called infantile spasms that may progress into recurrent seizures that are difficult to treat with medication. Children may also have yellow spots on their eyes because of lesions on their retina. Aicardi syndrome may also cause moderate to severe intellectual disabilities and developmental delays. Tumors and scoliosis may also be more common in those with Aicardi syndrome.

The gene responsible for causing Aicardi syndrome is currently unknown. However, because the condition primarily occurs in females, it is believed to be caused by a mutation of a gene on the X chromosome. More specficially, the short (p) arm of the X chromosome between bands 22.2 and 22.3 is being studied.

Humans have 23 pairs, or 46 chromosomes, in each cell. The last pair of chromosomes are called the sex chromosomes because they help to determine whether an individual will have male or female characteristics. Female individuals generally have two X chromosomes (46,XX) and males generally have one X and one Y chromosome (46,XY).

In order to equalize the amount of X chromosomes that have influence on the body, early in embryonic development, one copy of the X chromosome in cells other than egg cells will be permanently inactivated in female individuals. This process occurs randomly, meaning that the X chromosome that is inactivated in one cell might not be the same X chromosome that is inactivated in another cell. Each copy of the X chromosome in females is inactivated equally, or about 50% of the time. However, sometimes X-inactivation is not random, and one copy of the X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation.

When there is a severe gene mutation in one of the X chromosomes, skewed X-inactivation can occur. The cells in which the chromosome that has the mutation are active will not be able to survive as well making it appear as though X-inactivation is skewed. Skewed X-inactivation has been identified in girls with Aicardi syndrome, further supporting the idea that the disorder is caused by a mutation in a gene on the X chromosome.

Aicardi syndrome is classically defined in over 90% of cases by three cardinal features:

Major features of Aicardi syndrome include structural problems of the brain other than the missing or underdeveloped corpus callosum which is considered to be a classic feature of the condition; regions of neurons (nerves) in the brain did not move properly during development (heterotropia); cysts in the brain which can be found using a brain MRI; and problems with the optic disc or nerve.

Historically, the main symptoms of Aicardi syndrome included: 1) partial or complete absence of the structure (corpus callosum) that links the two halves of the brain 2) infantile spasms (a type of seizure disorder), and 3) chorioretinal lacunae, lesions on the retina (layer of nerves at the back of the eye) that look like yellowish spots.

Aicardi Syndrome Foundation
P.O. Box 3202
St. Charles, IL 60174
Phone: 800.374.8518
Email: web@aicardisyndrome.org
Website: www.aicardisyndrome.org

The Arc of the United States
1825 K Street, NW, Suite 1200
Washington, DC 20006
Phone: 202.534.3700
Toll-free: 800.433.5255
Fax: 202.534.3731
Email: Info@thearc.org
Website: www.thearc.org

March of Dimes
1275 Mamaroneck Avenue
White Plains, NY 10605
Phone: 914.997.4488
Toll-free: 888.MODIMES (663.4637)
Fax: 914.428.8203
Email: askus@marchofdimes.com
Website: www.marchofdimes.com

National Organization for Rare Disorders (NORD)
55 Kenosia Avenue
Danbury, CT 06810
Phone: 203.744.0100
Voice Mail: 800.999.NORD (6673)
Fax: 203.798.2291
Email: orphan@rarediseases.org
Website: www.rarediseases.org

National Eye Institute (NEI)
National Institutes of Health, DHHS
31 Center Drive, Rm. 6A32 MSC 2510
Bethesda, MD 20892-2510
Phone: 301.496.5248
Email: 2020@nei.nih.gov
Website: www.nei.nih.gov

National Institute of Mental Health (NIMH)
National Institutes of Health, DHHS
6001 Executive Blvd. Rm. 8184, MSC 9663
Bethesda, MD 20892-9663
Phone: 301.443.4513
Toll-free: 866.415.8051
TTY: 301.443.8431
Fax: 301.443.4279
Email: nimhinfo@nih.gov
Website: www.nimh.nih.gov

Other symptoms that can be associated with Aicardi syndrome include structural problems of the vertebrae, small or underdeveloped eyes (microphthalmia), the left and right sides of the brain being different sizes or shapes (cerebral asymmetry), and vascular malformations that can turn into tumors.

Newborn testing currently is not available for Aicardi syndrome as the specific gene responsible is unknown. However, a diagnosis can be made based on symptoms.

Aicardi syndrome is most commonly diagnosed by its symptoms, but because each child may present different symptoms, extra tests may be needed. A test that is often used to diagnose Aicardi syndrome is an MRI of the brain, which makes pictures of the brain to look for a small or missing corpus callosum and other problems with the formation of the brain. Those with Aicardi syndrome should also have an EEG to look at the brain waves to diagnose and treat seizures. An ophthalmologist (eye specialist) should look into the eyes at the retina to look for small cream-colored cavities (lacunae).

As of May 2019, there are clinical research trials underway for Aicardi syndrome. More information can be found by searching Aicardi syndrome at www.clinicaltrials.gov. The Aicardi Syndrome Foundation and the National Institute of Neurological Disorders and Stroke may also have information about current clinical research.

There is no cure for Aicardi syndrome nor is there a standard course of treatment. Most commonly, supportive treatment is used to manage the symptoms that are associated with Aicardi syndrome. The most common supportive treatment method for Aicardi syndrome involves managing the seizures and spasms that are brought on by the disease. A vagus nerve stimulator may be helpful in treating the seizures that accompany Aicardi syndrome. There are also programs to help both the children and their parents to cope with the intellectual disabilities that usually accompanies Aicardi syndrome.

Management of children with Aicardi syndrome is based on their clinical and developmental manifestations and may include a number of medical and therapeutic specialties such as pediatric neurology or epileptology, neurosurgery, ophthalmology, orthopedics, gastroenterology, physical therapy, speech therapy and occupational therapy.

Because Aicardi syndrome usually occurs randomly with no previous family history and is believed to be caused by new changes in the genetic code, the chance of having a second child with Aicardi syndrome is believed to be less than 1%.

Almost all of the reported cases of Aicardi syndrome have been sporadic or random meaning that they were not passed down from one generation to the next. New mutations are thought to be the cause of the condition. Parents of children with Aicardi syndrome are generally unaffected and other family members are not at increased risk.

Aicardi syndrome is classified as an X-linked dominant condition. While the gene associated with this disorder is not known, it is believed to be located on the X chromosome. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell is nearly always lethal very early in development, so almost all babies with Aicardi syndrome are female. However, a few affected males with an extra copy of the X chromosome in each cell (47,XXY) have been identified. Males with a 47,XXY chromosome pattern also have a condition called Klinefelter syndrome.

Donations can be made to the Aicardi Syndrome Foundation to better the quality of life of those children with Aicardi syndrome through research and awareness. Information about how to give money can be found on the Aicardi Syndrome Foundation website.

Aicardi syndrome is a very rare condition that occurs in approximately 1 of every 105,000 to 165,000 births in the United States but may be slightly more common in some other countries. It is estimated that there are currently several thousand individuals worldwide living with Aicardi syndrome. There does not appear to be any differences based on ethnicity.

Aicardi syndrome is most commonly diagnosed by its symptoms, but because each child may present different symptoms, extra tests may be needed. Some tests that are used to diagnose Aicardi syndrome include an MRI of the brain, which makes pictures of the brain to look for a small or missing corpus callosum and other problems with the formation of the brain. Those with Aicardi syndrome should also have an EEG to look at the brain waves to diagnose and treat seizures. An ophthalmologist (eye specialist) should look into the eyes at the retina to look for small cream-colored cavities called retinal lacunae.

Aicardi syndrome may also be known as the following names:

Families can register their child using sites such as [link url=”http://ouraicardilife.org/register/”]Our Aicardi Life or the [link url=”https://www.aicardisyndromefoundation.org”]Aicardi Syndrome’s Foundation website to receive newsletters and to read stories about other families with children with Aicardi syndrome. Additionally, popular social media sites such as Facebook can be great a great resource for connecting with other families who have had someone with Aicardi syndrome.

Over half of individuals with Aicardi syndrome have unusual facial features such as a short area between the upper lip and the nose (philtrum), a flat nose with an upturned tip, large ears, sparse eyebrows, and small or poorly developed eyes (microphthalmia). Other physical features of Aicardi syndrome may include small hands and/or hand malformations, and spinal and rib abnormalities leading to progressive abnormal curvature of the spine (scoliosis). Gastrointestinal problems such as constipation or diarrhea, gastroesophageal reflux, and difficulty feeding are also common.

Symptoms of the following disorders can be similar to those of Aicardi Syndrome.

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) can be confused with Aicardi syndrome. In MCLMR, the eye abnormalities are on the edges of the retinas, in contrast to Aicardi syndrome, where the lacunae are in the central part of the retina. Additionally in MCLMR, the head size is very small (severe microcephaly) whereas in Aicardi syndrome the head size is relatively normal. Additionally, individuals with MCLMR do not typically have agenesis of the corpus callosum or other developmental brain abnormalities typical of Aicardi syndrome.

Agenesis of the corpus callosum is a rare birth defect involving a partial or complete absence of the fibers that connect the right and left sides of the brain. Sometimes intellectual disability may result, but other cases may be without symptoms and the child may have normal intelligence. The early symptoms of this disorder may be grand mal or Jacksonian epileptic seizures. These may occur during the first weeks or within the first 2 years of life. Other early symptoms may include: abnormal accumulation of cerebrospinal fluid around the brain (hydrocephalus), impairment of mental development, and/or delays in physical development.

As of May 2019, there are no centers of excellence in Aicardi syndrome. One of the best ways to find a doctor familiar with caring for individuals with Aicardi syndrome is to talk with other parents at the Aicardi Syndrome Foundation.