What Is Aicardi Syndrome?

Aicardi Syndrome is a rare genetic disorder that primarily affects people assigned female at birth (AFAB) and is characterized by the absence of a structure in the brain called the corpus callosum, as well as abnormalities in the retina (the light-sensitive part of the eye) and seizures.^1,2,3 The corpus callosum is part of the brain that connects the two hemispheres and helps them communicate with each other. The absence of corpus callosum or corpus callosum agenesis results in both developmental and intellectual delays.

The mortality rate of children with aicardi syndrome is high and the overall prognosis for those affected is poor. Children with aicardi syndrome often experience significant developmental delays, including delays in motor skills, speech, and cognition. As a result, they require extensive medical and therapeutic support throughout their lives in order to manage their symptoms and improve their overall quality of life.

Aicardi syndrome is a very rare condition and most people with this disorder have a unique combination of symptoms. Despite the severity of Aicardi syndrome, early diagnosis and prompt, effective medical and therapeutic intervention can help to improve outcomes for affected individuals. This may include medication, physical therapy, and other interventions aimed at managing symptoms and improving overall health and well-being.

Overview

Aicardi syndrome is a complex and heterogeneous condition with a so-called classic triad of features which include infantile spasm, corpus callosum agenesis and retinal lesions. Although, not every affected individual will present with all three features of the classic triad. 

The variability of symptoms and the complex causes of this rare disorder make it challenging to provide a clear and concise overview of the outcome of Aicardi syndrome. However, it is generally agreed that the prognosis is poor, with a high risk of severe neurological and developmental disabilities, as well as other health problems.

Despite these challenges, it is important to note that early diagnosis and prompt, effective medical and therapeutic intervention can help to improve outcomes for the affected individual.  

Causes of aicardi syndrome

Aicardi syndrome was first described by Jean Aicardi in 1965. The exact cause of Aicardi syndrome is not known, but it is believed to be a genetic condition.  

There is evidence to suggest that Aicardi syndrome may be caused by new pathogenic changes in a gene on the X chromosome that is subject to X-chromosome inactivation. However, no specific gene has been identified as the cause of the condition. 

X-chromosome inactivation is a process by which one of the two X chromosomes present in people AFAB is randomly inactivated early in embryonic development, with the same X-chromosome remaining inactivated in all subsequent cells. This process ensures that people, who have two X chromosomes have a similar amount of X-linked gene expression as people assigned male at birth (AMAB), who have only one X chromosome.

Aicardi syndrome may result from a change in a gene on the X chromosome that disrupts the normal process of X-chromosome activation. This may result in the abnormal expression of the gene in certain cells, leading to the development of the characteristic features of Aicardi syndrome.

Further research is needed to identify the specific gene or genes responsible for this syndrome and to better understand the mechanisms underlying the development of the condition. 

Signs and symptoms of aicardi syndrome

The clinical presentation of Aicardi syndrome is highly variable and can range from mild to severe. The symptoms of the condition can affect various parts of the body, including the central nervous system, skeletal system, and other organs.

Agenesis of the corpus callosum (the structure that connects the two hemispheres of the brain) is a hallmark of aicardi syndrome and can be partial or complete.

Other common findings in the central nervous system include such brain defects as microcephaly (small head size), microgyria (abnormal folds in the brain), cysts, cortical heterotopia (abnormal migration of brain cells), psychomotor or developmental delay, axial hypotonia (low muscle tone in the trunk), bilateral pyramidal signs (abnormal muscle control), and swallowing difficulties.

Severe complex seizures and anomalies on electroencephalography (EEG) are also commonly seen in affected individuals. In addition to neurological disorders, a variety of other anomalies have been observed in affected individuals, including skeletal anomalies, tumours, and other disturbances in cell/tissue differentiation. Choroid plexus papillomas, arachnoid cysts, and retrobulbar cysts in the central nervous system have also been reported. 

Outside the central nervous system,  teratomas and other non-aggressive tumourshave been observed.

Not all affected individuals will exhibit all of these symptoms, and the severity and specific symptoms can vary greatly from one individual to another. The complex and highly variable presentation of aicardi syndrome highlights the need for a comprehensive evaluation of affected individuals and the importance of ongoing monitoring and management to address the diverse needs of affected individuals and their families.

Management and treatment for aicardi syndrome

Anti-seizure medications are the mainstay of treatment for seizures in aicardi syndrome. The choice of medication depends on the type and severity of seizures and the individual patient's response to the medication. Corticosteroids have also been used to control infantile spasms, but their long-term use is limited due to their potential side effects.

In some cases, surgical intervention may be necessary to control seizures that are not responsive to medical treatment. The surgical options may include corpus callosotomy, hemispherotomy, and lobectomy, depending on the location and type of seizures.

Children with aicardi syndrome often have difficulty with feeding and swallowing, which can lead to malnutrition and a failure to thrive. A team approach including a speech therapist and a dietitian can help with the management of feeding and nutritional issues.

Children with aicardi syndrome are at risk for aspiration (inhalation of foreign materials) due to their difficulty with feeding and swallowing, as well as other factors such as weakened muscles and abnormal spinal curvatures. Close monitoring of respiratory function is necessary to prevent respiratory complications.

Children with aicardi syndrome require specialized educational support to meet their developmental and cognitive needs. An individualized education plan (IEP) is necessary to ensure that their educational needs are met.

Overall, the management of aicardi syndrome requires a comprehensive and multidisciplinary approach, involving a pediatric neurologist, physical therapist, occupational therapist, speech therapist, dietitian, and educational specialist.

FAQs

How is aicardi syndrome diagnosed?

Aicardi syndrome is a complex disorder that can be challenging to diagnose.^4,5 The following are some of the tests and procedures used in the diagnosis of aicardi syndrome:

• Neurological examination: A comprehensive neurological examination is performed to assess the child's motor and cognitive abilities, as well as their muscle tone, reflexes, and coordination
• Electroencephalogram (EEG): This is a test that records the electrical activity of the brain and is used to detect abnormal patterns of electrical activity associated with seizures
• Magnetic resonance imaging (MRI): An MRI can show structural abnormalities in the brain, such as the absence of the corpus callosum, which is a hallmark of aicardi syndrome
• Genetic testing: A genetic test can be performed to detect mutations in the X-linked genes that are associated with aicardi syndrome. This test can provide a definitive diagnosis, but it is not always necessary for a diagnosis of aicardi syndrome to be made
• Clinical criteria: A diagnosis of aicardi syndrome can also be made based on the clinical criteria, including the presence of infantile spasms, chorioretinal scarring, and the absence of the corpus callosum

Aicardi syndrome can be challenging, and some children may have a similar clinical presentation but have a different underlying condition. Therefore, it's important to have a team of healthcare professionals with expertise in the diagnosis and management of aicardi syndrome involved in the diagnostic process.

How can I prevent aicardi syndrome?

Aicardi syndrome is a genetic disorder that is caused by mutations in the X-linked genes. There is no known way to prevent aicardi syndrome. The condition is not caused by environmental factors or lifestyle choices. It occurs randomly and is not related to anything the parents did or did not do before, during or after pregnancy.

However, early diagnosis and treatment of aicardi syndrome can help improve outcomes and prevent or mitigate potential complications associated with the condition. It's important for parents to seek medical evaluation for their child if they have concerns about their development or if they have a family history of aicardi syndrome. 

Early intervention and support can help children with aicardi syndrome reach their full potential and lead fulfilling lives.

Who are at risk of aicardi syndrome?

Aicardi syndrome is a rare genetic disorder that affects only people with two X chromosomes. The condition is caused by a genetic mutation, and it is most commonly diagnosed in infants and young children. There is no cure for aicardi syndrome, and the prognosis for affected individuals is poor.

Aicardi syndrome is not known to have a specific genetic pattern of inheritance, meaning that it is not caused by a single gene and cannot be passed from one generation to the next. Instead, the condition appears to result from a new genetic mutation that occurs spontaneously in some individuals.

Since aicardi syndrome only affects only those with two X chromosomes, the main risk factor for the condition is simply being assigned female at birth. Beyond that, there are no specific risk factors for the development of aicardi syndrome.

How common is aicardi syndrome?

Aicardi syndrome is a rare condition, and the exact incidence and prevalence are difficult to determine due to the variability of symptoms and the rarity of the condition. 

Aicardi syndrome is estimated to affect between 1 in 105,000 and 1 in 167,000 individuals in the United States, and between 1 in 93,000 and 1 in 99,000 individuals in some European countries. The estimated global prevalence of aicardi syndrome is over 4,000 individuals. It is important to note that these estimates are based on limited data and may not accurately reflect the true incidence and prevalence of the condition. 

Further research is needed to better understand the epidemiology of aicardi syndrome and to improve our understanding of the condition and its impact on affected individuals and their families.

When should I see a doctor?

If you suspect that your child may have aicardi syndrome or if they are showing symptoms of the condition, it is important to see a doctor as soon as possible. The earlier aicardi syndrome is diagnosed, the earlier appropriate treatment and support can be provided.

Common symptoms of aicardi syndrome include:

• Seizures (often the first sign of the condition)
• Developmental delay or intellectual disability
• Absence of a corpus callosum (the structure that connects the two hemispheres of the brain)
• Abnormal eye movements
• Vision loss
• Abnormalities of the spine and other bones

The doctor will be able to conduct a thorough evaluation and may order tests such as an MRI or CT scan to confirm the diagnosis of aicardi syndrome.

Once a diagnosis has been made, the doctor will work with you to develop a treatment plan that addresses your child's specific needs and helps them manage their symptoms as effectively as possible.

Summary

Aicardi syndrome is a rare genetic disorder that primarily affects people assigned female at birth and is characterized by the absence or underdevelopment of a structure in the brain called the corpus callosum, as well as seizures and other neurological symptoms. It is also important to note that aicardi syndrome can sometimes be difficult to diagnose, as it is a rare condition and its symptoms can be similar to other neurological disorders. 

If your child has been previously diagnosed with a different neurological disorder but you suspect they may have aicardi syndrome, it may be worth seeking a second opinion from a doctor who is knowledgeable about the condition.

References

1. Aicardi J, Levebre J, Lerique-Koechlin A. A new syndrome: Spasms in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol. 1965;19:609–10
2. Sutton VR, Van den Veyver IB. Aicardi Syndrome. 2006 Jun 30 [Updated 2020 Nov 12]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.
3. Aicardi, Jean. ‘Aicardi Syndrome’. Brain and Development, vol. 27, no. 3, Apr. 2005, pp. 164–71. DOI.org (Crossref), https://doi.org/10.1016/j.braindev.2003.11.011.
4. Cuenca, Nury Tatiana Rincón, et al. ‘Diagnostic Approach to Aicardi Syndrome: A Case Report’. Radiology Case Reports, vol. 17, no. 9, Sept. 2022, pp. 3035–39. DOI.org (Crossref), https://doi.org/10.1016/j.radcr.2022.05.067.
5. Pomar, Léo, et al. ‘Prenatal Diagnosis of Aicardi Syndrome Based on a Suggestive Imaging Pattern: A Multicenter Case‐series’. Prenatal Diagnosis, vol. 42, no. 4, Apr. 2022, pp. 484–94. DOI.org (Crossref), https://doi.org/10.1002/pd.6085.

This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Maja Mandzikashvili

Master of Genetics, Public Health educator-Vilnius University.

Hi, I am public health specialist, working on educational projects for kids.
While self-love and healthy habits like exercise and a balanced diet can contribute to physical and psychological well-being, achieving a "perfect" body is subjective and can be unrealistic or harmful to pursue. All bodies are beautiful to me when they are healthy physically and mentally.
This is the approach to my daily practice in life and at work, I am trying to maintain and teach my pupils.
I am glad that through my articles I can share my knowledge and experience with others to promote healthy habits and prevent disease.

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