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Aicardi Syndrome Clinical Presentation

  • Author: Ravi Sunderkrishnan, MD; Chief Editor: Maria Descartes, MD  more...
 
Updated: Mar 31, 2016
 

History

See the list below:

  • Aicardi syndrome is often diagnosed in female infants only after the onset of seizures or when the presence of dysmorphic facies prompts further evaluation.
  • If only visual abnormalities or developmental delays are present, the condition may not be recognized until the onset of seizures, or if ophthalmologic evaluations demonstrate characteristic chorioretinal lacunae, which are considered pathognomonic for Aicardi syndrome and are shown in the images below.
    Cross-section of an eye in a patient with Aicardi Cross-section of an eye in a patient with Aicardi syndrome. The arrow indicates chorioretinal lacunae.
    Chorioretinal lacunae. Chorioretinal lacunae.
  • Ocular abnormalities limit visual ability and are blinding in some children. A less common presentation is that of retro-orbital cysts and optic nerve hypoplasia. [11]
  • Presumably, asymptomatic children who have not undergone neuroimaging in utero are not recognized unless they are incidentally screened by an ophthalmologist or brain imaging specialist.
  • Some children are diagnosed in utero with brain-structure abnormalities. Most often, the absence of the corpus callosum on the fetal ultrasonogram prompts further imaging studies.
  • Anomalies of the sulci and gyri, periventricular heterotopia, associated cerebellar and brain stem anomalies with absent corpus callosum, can also be evaluated with magnetic resonance imaging (MRI) to aid in the diagnosis and to better determine the prognosis in Aicardi syndrome. [11]
  • Seizures are a common initial manifestation, most frequently infantile spasm. Chevrie et al reported 97% of patients had infantile spasm, and most of these had seizures when younger than 3 months. [12] Additional seizure types noted include hemiconvulsions, complex partial seizures, and focal motor seizures.
  • Electroencephalogram (EEG) findings are not consistent. In the relevant clinical scenario, a burst suppression pattern arising independently from each hemisphere suggests Aicardi syndrome. The most common EEG tracing is bursts of high-amplitude slow and sharp waves separated by intervals of low amplitude.
  • Global developmental delay is uniform, and most patients have moderate-to-severe mental retardation. This characteristic is probably due to the combination of brain dysgenesis and intractable epilepsy, although some children may walk and, in rare cases, develop expressive language.
  • Most of these children are unable to walk, due to spastic hemiplegia, and are bedridden. Children with Aicardi syndrome typically lack even rudimentary abilities to interact with their environments.
  • Certain malignancies develop more frequently, including embryonic soft-tissue carcinoma, hepatoblastoma, and angiosarcoma.
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Physical

Neurodevelopmental

The neurologic examination can reveal microcephaly, axial hypotonia, appendicular hypertonia with spasticity that often affects one side, and brisk deep tendon reflexes, as well as hemiparesis.[13]

Moderate-to-severe global developmental delay and intellectual disability is expected, but individuals with only mild or no learning disabilities or developmental delay have been reported.

Infantile spasms, seizures, or epilepsy develop before age 3 months. Electroencephalography (EEG) can reveal asynchronous multifocal epileptiform abnormalities with burst suppression and dissociation between the two hemispheres.

Ocular

Pathognomonic lesions, called chorioretinal lacunae, commonly cluster around the optic disc of the eye and are described as punched-out, white or yellow defects. These lesions characteristically lack pigment, a characteristic that helps to distinguish them from lesions seen in infectious chorioretinitis. Classic chorioretinal lacunae do not enlarge or progress. Although other ocular lesions are present in Aicardi syndrome, this manifestation is pathognomonic for diagnosis.[14]

Other common ocular lesions include the following:

  • Microphthalmos
  • Retrobulbar cyst
  • Cataract
  • Coloboma
  • Retinal detachment
  • Iris synechiae
  • Remnants of fetal pupillary membrane

Craniofacial

Microcephaly, hemifacial asymmetry, microphthalmia, or plagiocephaly may be present. Short philtrum and cleft lip and palate are also seen.

Gastrointestinal

Constipation, gastroesophageal reflux, diarrhea, and feeding difficulties are perceived by parents to be the second most difficult problem to manage after seizures.[8]

Extremities

Small hands, along with an increased incidence of hand malformations, have been reported.

Musculoskeletal

Costovertebral abnormalities, such as hemivertebrae, fused or butterfly vertebrae, and rib abnormalities, may be present.

Scoliosis resulting from these deformities can be disfiguring and disabling. A study by Grigoriou et al indicated that Aicardi syndrome–related scoliosis progresses rapidly and does not respond to bracing. Scoliosis was first noticed in the study’s patients at a mean age of 3.9 years, at which time the mean Cobb angle was 22.5%, while the patients’ first orthopedic visit took place at a mean age of 5.8 years, when the progressed mean Cobb angle was 39.5%.[15]

 

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Causes

See the list below:

  • The exact mutation and cause of the mutation in Aicardi syndrome are still unknown and disputed.
  • Events early in gestation, probably in weeks 4-8, are suspected causes. Because it has been shown to not affect the twin of the patient with Aicardi syndrome, the potential etiologies of prenatal hypoxia or toxin are no longer in favor. [13]
  • A genetic basis for the syndrome is favored, specifically an X-linked dominant mutation with lethality in male hemizygotes. The Xp22 gene was thought to be the culprit gene.
  • Spontaneous mutation is most likely, because siblings appear to be spared and have not been reported in parents of an affected female.
  • The only affected male patients have been described as having an XXY genotype. The presence of Aicardi syndrome in males with a 46,XY karyotype has been disputed, but new cases have been reported. It is possible that these cases are caused by mosaic mutations of the gene. [13]
  • Skewed X chromosome inactivation may account for some clinical heterogeneity. [16]
  • According to one report, another etiologic possibility remains in which Aicardi syndrome may be caused by a new mutation on an autosome (eg. 1p36 gene), with sex-limited expression in females. [13]
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Contributor Information and Disclosures
Author

Ravi Sunderkrishnan, MD Fellow in Nephrology, Thomas Jefferson University Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

James Bowman, MD Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago

James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical and Translational Research, College of American Pathologists

Disclosure: Nothing to disclose.

Acknowledgements

Ronald G Davis, MD, MPH, FAAP Assistant Clinical Professor, Child Neurology, Florida State University; Owner and Medical Director of Pediatric Neurology, PA and Pediatric Neurology Epilepsy Center of Central Florida; Medical Director of Epileptology, Arnold Palmer Hospital for Women and Children in Orlando, Florida; Medical Director, Central Florida Muscular Dystrophy Association Clinic

Ronald G Davis, MD, MPH, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose. Marc P DiFazio, MD Associate Professor, Department of Neurology, Uniformed Services University of the Health Sciences; Director, Pediatric Subspecialty Services, Shady Grove Adventist Hospital for Children

Marc P DiFazio, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Cerebral Palsy and Developmental Medicine, American Academy of Neurology, Child Neurology Society, and Movement Disorders Society

Disclosure: Nothing to disclose.

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Cross-section of an eye in a patient with Aicardi syndrome. The arrow indicates chorioretinal lacunae.
Chorioretinal lacunae.
 
 
 
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