Aicardi Syndrome Causes, Symptoms, Diagnosis, Treatment, Prevention

Aicardi Syndrome Causes, Symptoms, Diagnosis, Treatment, Prevention


What is Aicardi Syndrome?


Aicardi syndrome is a rare genetic disorder that primarily affects newborn girls. The condition is sporadic, meaning it is not known to pass from parent to child. (An exception is a report of two sisters and a pair of identical twins, all of whom were affected.) The mutation that causes Aicardi syndrome has not been identified. Scientists believe that the gene associated with the condition is located on the X chromosome because nearly all affected individuals are female and the only reports of boys having Aicardi syndrome are in boys born with an extra "X" chromosome. (Females have two X chromosomes, while males normally have an X and a Y chromosome.) Girls with Aicardi syndrome often develop seizures prior to three months and most before one year of age.

Originally, Aicardi syndrome was characterized by three main features: 1) partial or complete absence of the structure (corpus callosum) that links the two halves of the brain (2) complex seizures, generally starting as infantile spasms, and 3) retinal lacunae, lesions on the retina that look like yellowish spots. However, Aicardi syndrome is now known to have a much broader spectrum of abnormalities than was initially described. Not all girls with the condition have the three features described above and many girls have additional features.

Typical findings in the brain of girls with Aicardi syndrome include heterotopias, which are groups of brain cells that, during development, migrated to the wrong area of brain; polymicrogyria or pachygyria, which are numerous small, or too few, brain folds; and cysts, (fluid filled cavities) in the brain. Girls with Aicardi syndrome have varying degrees of mental retardation and developmental delay. Many girls also have developmental abnormalities of their optic nerves and some have microphthalmia (small eyes). Skeletal problems such as absent or abnormal ribs and abnormalities of vertebrae in the spinal column (including hemivertebrae and butterfly vertebrae) have also been reported. Some girls also have skin problems, facial asymmetry, or other characteristic facial features.

(Aicardi syndrome is distinct from Aicardi-Goutieres syndrome, which is an inherited encephalopathy that affects newborn infants.)

The Causes and Risk Factors For Aicardi Syndrome


Scientists believe that Aicardi syndrome is caused by a defect in the X chromosome—and the condition appears most often in girls. It can also be present in boys with Klinefelter syndrome, a disorder where a male has an extra X chromosome.

During normal development of an embryo, there should only be one active X chromosome in each cell. This means that X chromosomes must randomly deactivate during cell formation. In the case of Aicardi syndrome, scientists theorize that these chromosomes do not alternate randomly as they should and one X chromosome takes part in more than half of the body’s cell formations. This is called skewed X-activation.

Scientists have yet to pinpoint the exact gene that causes skewed X-activation. Thus, the precise cause of the disorder is still not known. This lack of information makes it difficult to pinpoint the risk factors for Aicardi 
syndrome.

Symptoms of Aicardi Syndrome


The girls usually appear healthy at birth and develop normally during the first months, but later manifest different symptoms which can be traced to brain malformations. A characteristic malformation is when the corpus callosum, which normally connects the two hemispheres of the brain, is partially or entirely absent (corpus callosum agenesis). Usually there are other abnormalities including groups of brain cells presenting in an incorrect location (heterotopia), abnormal folding in the cerebral cortex (agyria) or differently-sized hemispheres of the brain. There are often fluid-filled pockets in the brain (plexus cysts) which, if large, may require an operation. Girls with the condition often have a small head (microcephaly).

Between the ages of three and six months they often experience infantile spasms, a type of epileptic seizure. These spasms are caused by anomolies in the grey matter of the brain, a component of the cerebral cortex. They may take the form of flexor spasms (when the child’s neck is suddenly bent forward at the same time that the arms are pulled upward in a clenched position) or one of various forms of infantile seizures. The attacks come in a series at short intervals and can vary in number from day to day. Initially they may be non-specific although severe enough to cause parents to contact medical services. In Aicardi syndrome, epilepsy is usually very difficult to treat and remains a life-long condition.

The eyes are always affected. In an eye examination, areas lacking pigment (retinal lacunae) can be identified as white patches on the fundus. Pigment cells and other structures are lacking in these areas of the retina. If lacunae are located on the macula (the yellow spot), this will affect vision. Other types of eye malformations are common: one eye may be smaller than the other (microphthalmia), the optic nerve may be defective and there may be a slit in one of the membranes of the eye (coloboma). As girls with Aicardi syndrome have an intellectual disability which makes it difficult for them to participate actively in a vision test, it is difficult to measure how much they can see. However, most are visually impaired without being blind. This visual impairment may be associated with the reduced ability of the brain to produce and interpret visual images. Vision does not deteriorate over time and the degree of impairment is thought to remain constant.

Most girls with the condition have a severe intellectual disability and do not learn to walk or talk. A few have a moderate intellectual disability and learn to speak a few words and take some steps. It is common that these girls drool, grind their teeth and have problems eating. There are also girls whose intellectual disability is less severe, but this is very rare.

Extra or absent ribs and abnormalities in the vertebrae are also common. As the girls are growing up, many develop curvature of the spine (scoliosis). Isolated cases of malignant brain and other tumours have been reported during the early years of life.

How is Aicardi Syndrome Diagnosed?


Examination of the eye to look for abnormalities.

Computed tomography (CT scan) or magnetic resonance imaging (MRI) of the head can confirm the absence of the connection between two sides of the brain and rule out other possible causes of fits and developmental delay.

Electroencephalogram (EEG) can be used to help determine the type and severity of seizures.
Gene studies should be done.

Treatment/interventions for Aicardi Syndrome


Girls with Aicardi syndrome and their parents are in early contact with many health care professionals. For this reason, it is important that measures are coordinated.

Medication usually prescribed in cases of infantile spasm and epilepsy is also prescribed for girls with Aicardi syndrome. As types of seizures vary greatly and change character, epilepsy is often difficult to treat. Medication is prescribed on the basis of type of seizure, EEG results and effectiveness.

As abnormalities causing seizures are found in many places in the brain, surgery to relieve epilepsy has only rarely produced positive results in treating Aicardi syndrome.

As an alternative treatment to control epilepsy, a ketogenic diet may be considered. This is a high-fat, low-carbohydrate diet which alters the metabolism. In certain children, this leads to a reduction in seizures. The treatment should bemonitored by a physician and dietician who have experience of this diet and work in collaboration.

If other forms of treatment do not work, vagus nerve stimulation can be used as an alternative method of reducing or preventing seizures. The vagus nerve is one of the twelve cranial nerves that emerge directly from the brain. A vagus nerve stimulator is a small electronic device connected to the nerve in the neck. A battery is implanted in the area below the left collarbone, and the device sends electrical impulses to the brain via the vagus nerve, which controls activity between the brain and many internal organs. Treatment is available after investigations have been carried out at one of Sweden’s university hospitals.

It is important that the girls’ residual vision is preserved as far as possible. The children should therefore be examined at an early stage by a paediatric opthalmologist in order to establish levels of vision, as far as possible, as well as the need for vision aids.

Greatly enhanced preventive dental care and contact with paediatric dental specialists (paedodontists) is necessary as the girls can have problems brushing and looking after their teeth.

Because of the risk of developing scoliosis, the girls’ backs should be examined regularly. 
Scoliosis can be treated with a back brace or corset, and sometimes requires surgical intervention.

Habilitation


To stimulate development and compensate for loss of function, children with the syndrome may need early habilitation treatment, including support to help deal with visual impairments. Early contact should be established with a habilitation team, which includes professionals with special expertise in how disability affects everyday life, health and development. Support and treatment take place within the medical, educational, psychological, social and technical fields. Help includes assessment, treatment, the provision of aids, information on the specific disability, and counselling. It also includes information on all available support offered in the community, as well as advice on adjustments to the home environment and other places where the child spends time. The family may also need help in coordinating different measures.

The measures focus on the needs of the child and family, may vary over time, and always take place in collaboration with individuals close to the child. To develop the child’s communicative abilities it is important to work with augmentative and alternative communication from an early stage (AAC).

There should be close contact with the local authority, which can offer different kinds of help including personal assistance, a contact family or short-term accommodation, to make daily life easier.

Adults


Aicardi syndrome is a non-progressive, non-degenerative condition. However, very little is known about the long-term prognosis. There are a few cases studies where epilepy has become milder with increasing age.

Adult women with the syndrome require continued habilitation and support, adapted to their individual, daily needs. This may take the form of support and care in accommodation offering specialist services and daily activities.

Prevention for Aicardi Syndrome


There are currently no known ways to prevent Aicardi syndrome. However, a number of treatment options exist that allow patients to manage some of the symptoms. Genetic testing is not currently available, because no specific genetic mutation has been implicated in Aicardi syndrome.

What Is The Long-Term Outlook For a Child With Aicardi Syndrome?


Those with Aicardi syndrome have a higher chance of dying during childhood and their prognosis greatly depends on the intensity of their symptoms. Nearly all children with the syndrome have some form of mild to severe mental retardation. Some children with Aicardi syndrome are able to speak and walk by themselves while others may need support to walk. They will likely be completely dependent and need a caretaker for the rest of their lives.

What research is being done?


The NINDS supports and conducts research on neurogenetic disorders such as Aicardi syndrome. The goals of this research are to locate and understand the genes involved and to develop techniques to diagnose, treat, prevent, and ultimately cure disorders such as Aicardi syndrome.