Aicardi syndrome

Overview

Aicardi syndrome is a rare genetic neurological disorder that primarily affects females and is characterized by a classic triad of features: absence of the corpus callosum (the structure that connects the two hemispheres of the brain), distinctive chorioretinal lacunae (lesions in the retina), and infantile spasms (a form of epilepsy). It typically presents in early infancy and often leads to significant developmental delays and intellectual disability. First described by Dr. Jean Aicardi in 1965, this syndrome is considered a congenital disorder of brain development.

Causes

Aicardi syndrome is believed to be caused by a mutation on the X chromosome. The exact gene responsible has not yet been definitively identified, but the disorder follows an X-linked dominant inheritance pattern that is thought to be lethal in males. This explains why nearly all reported cases occur in females or, very rarely, in males with XXY (Klinefelter) syndrome. In most cases, the mutation is sporadic (not inherited) and arises de novo during embryonic development.

Symptoms

The symptoms of Aicardi syndrome typically appear within the first few months of life and include:

Neurological Symptoms:

• Infantile spasms: Sudden, jerking seizures typically beginning between 3 and 5 months of age

• Developmental delays: Delayed motor skills and cognitive milestones

• Intellectual disability: Ranges from moderate to severe

• Microcephaly: Small head size in some cases

Ophthalmologic Features:

• Chorioretinal lacunae: Circular or oval lesions in the retina detectable on eye exam

• Colobomas or optic nerve abnormalities

• Vision problems or blindness

Other Features:

• Corpus callosum agenesis: Complete or partial absence

• Scoliosis or other skeletal anomalies

• Cysts or abnormal tissue in the brain

• Gastrointestinal and feeding difficulties

Diagnosis

Diagnosis of Aicardi syndrome is based on clinical findings and confirmed through a combination of neurological and ophthalmological assessments. Key diagnostic steps include:

• Brain imaging (MRI or CT scan): To identify agenesis of the corpus callosum and brain cysts

• EEG: Often shows a pattern called "burst suppression" during infantile spasms

• Ophthalmologic exam: To detect chorioretinal lacunae and other eye abnormalities

• Genetic testing: May help rule out other syndromes, though no specific gene for Aicardi syndrome has been pinpointed

Treatment

There is currently no cure for Aicardi syndrome. Treatment focuses on managing symptoms and improving quality of life through a multidisciplinary approach:

Seizure Management:

• Antiepileptic drugs (e.g., vigabatrin, ACTH)

• Ketogenic diet or vagus nerve stimulation (in refractory cases)

Developmental Support:

• Physical, occupational, and speech therapy

• Special education and early intervention programs

Supportive Care:

• Management of feeding difficulties, often requiring gastrostomy tube (G-tube)

• Treatment of scoliosis and orthopedic issues

• Regular eye and neurological evaluations

Prognosis

The prognosis for Aicardi syndrome varies depending on the severity of neurological involvement and the effectiveness of seizure control. Many children with Aicardi syndrome experience significant developmental delays and require lifelong care. While life expectancy is reduced in severe cases, some individuals may live into adolescence or adulthood with supportive care. Early diagnosis, appropriate therapies, and proactive management of complications can help improve the quality of life for affected individuals and their families.