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Aicardi Syndrome Clinical Presentation

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


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.



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.


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


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


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


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


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]




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]
Contributor Information and Disclosures

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.


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.

  1. Aicardi J, Lefebvre J, Lerique-Koechlin A. A new syndrome: spasm in flexion, callosal agenesis, ocular abnormalities. Electroencephalogr Clin Neurophysiol. 1965. 19:609-10.

  2. Dennis J, Bower BD. The Aicardi syndrome. Dev Med Child Neurol. 1972 Jun. 14(3):382-90. [Medline].

  3. Steffensen TS, Gilbert-Barness E, Lacson A, Margo CE. Cerebellar migration defects in aicardi syndrome: an extension of the neuropathological spectrum. Fetal Pediatr Pathol. 2009. 28(1):24-38. [Medline].

  4. Study of Selected X-Linked Disorders: Aicardi Syndrome. Available at

  5. Kroner BL, Preiss LR, Ardini MA, Gaillard WD. New incidence, prevalence, and survival of Aicardi syndrome from 408 cases. J Child Neurol. 2008 May. 23(5):531-5. [Medline].

  6. Lund C, Bjornvold M, Tuft M, Kostov H, Rosby O, Selmer KK. Aicardi syndrome: an epidemiologic and clinical study in Norway. Pediatr Neurol. 2015 Feb. 52 (2):182-6.e3. [Medline].

  7. Kroner BL, Preiss LR, Ardini MA, Gaillard WD. New incidence, prevalence, and survival of Aicardi syndrome from 408 cases. J Child Neurol. 2008 May. 23(5):531-5. [Medline].

  8. Glasmacher MA, Sutton VR, Hopkins B, Eble T, Lewis RA, Park Parsons D. Phenotype and management of Aicardi syndrome: new findings from a survey of 69 children. J Child Neurol. 2007 Feb. 22(2):176-84. [Medline].

  9. Zubairi MS, Carter RF, Ronen GM. A male phenotype with Aicardi syndrome. J Child Neurol. 2009 Feb. 24(2):204-7. [Medline].

  10. Prontera P, Bartocci A, Ottaviani V, Isidori I, Rogaia D, Ardisia C, et al. Aicardi syndrome associated with autosomal genomic imbalance: coincidence or evidence for autosomal inheritance with sex-limited expression?. Mol Syndromol. 2013 Apr. 4(4):197-202. [Medline]. [Full Text].

  11. Sandhu PS, Khong K, McGahan JP, Ro K, Lloyd WC 3rd, Towner D. Novel presentation of Aicardi syndrome with agenesis of the corpus callosum and an orbital cyst. J Ultrasound Med. 2010 May. 29(5):843-6. [Medline].

  12. Chevrie J, Aicardi J. The Aicardi syndrome. Pedley T, Meldrum B, eds. Recent Advances in Epilepsy. Edinburgh and London, England: Churchill Livingstone; 1986. 189-210.

  13. Sutton VR, Van den Veyver IB. Aicardi Syndrome. June 2006. [Full Text].

  14. Shah PK, Narendran V, Kalpana N. Aicardi syndrome: the importance of an ophthalmologist in its diagnosis. Indian J Ophthalmol. 2009 May-Jun. 57(3):234-6. [Medline]. [Full Text].

  15. Grigoriou E, DeSabato JJ, Colo D, Dormans JP. Scoliosis in Children With Aicardi Syndrome. J Pediatr Orthop. 2015 Jul-Aug. 35 (5):e38-42. [Medline].

  16. Eble TN, Sutton VR, Sangi-Haghpeykar H, Wang X, Jin W, Lewis RA, et al. Non-random X chromosome inactivation in Aicardi syndrome. Hum Genet. 2009 Mar. 125(2):211-6. [Medline]. [Full Text].

  17. Hopkins B, Sutton VR, Lewis RA, Van den Veyver I, Clark G. Neuroimaging aspects of Aicardi syndrome. Am J Med Genet A. 2008 Nov 15. 146A(22):2871-8. [Medline].

  18. Hergan B, Atar OD, Poretti A, Huisman TA. Serial fetal MRI for the diagnosis of Aicardi syndrome. Neuroradiol J. 2013 Aug. 26(4):380-4. [Medline].

  19. Kasasbeh AS, Gurnett CA, Smyth MD. Palliative epilepsy surgery in Aicardi syndrome: a case series and review of literature. Childs Nerv Syst. 2014 Mar. 30(3):497-503. [Medline].

  20. [Guideline] Laurino MY, Bennett RL, Saraiya DS, et al. Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2005 Jun. 14(3):165-81. [Medline]. [Full Text].

  21. Aicardi J. Aicardi syndrome. Brain Dev. 2005 Apr. 27(3):164-71. [Medline].

  22. Chau V, Karvelas G, Jacob P, Carmant L. Early treatment of Aicardi syndrome with vigabatrin can improve outcome. Neurology. 2004 Nov 9. 63(9):1756-7. [Medline].

  23. Darwish H. Aicardi syndrome. Gilman S, Goldstein G, eds. Neurobase. San Diego, CA: Arbor Publishing Corp; 1999. Vol 2:

  24. Hamano S, Yagishita S, Kawakami M, et al. Aicardi syndrome: postmortem findings. Pediatr Neurol. 1989 Jul-Aug. 5(4):259-61. [Medline].

  25. Hopkins B, Sutton VR, Lewis RA, Van den Veyver I, Clark G. Neuroimaging aspects of Aicardi syndrome. Am J Med Genet A. 2008 Nov 15. 146A(22):2871-8. [Medline]. [Full Text].

  26. Kobayashi K, Oka M, Akiyama T, et al. Very fast rhythmic activity on scalp EEG associated with epileptic spasms. Epilepsia. 2004 May. 45(5):488-96. [Medline].

  27. Kobayashi K, Oka M, Inoue T, et al. Characteristics of slow waves on EEG associated with epileptic spasms. Epilepsia. 2005 Jul. 46(7):1098-105. [Medline].

  28. [Guideline] Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004 May 25. 62(10):1668-81. [Medline]. [Full Text].

  29. Menezes A, MacGregor D, Buncic J. Aicardi syndrome: natural history and possible predictors of severity. Pediatr Neurol. 1994 Nov. 11(4):313-8. [Medline].

  30. Menezes AV, Enzenauer RW, Buncic JR. Aicardi syndrome--the elusive mild case. Br J Ophthalmol. 1994 Jun. 78(6):494-6. [Medline]. [Full Text].

  31. Neidich J, Nussbaum R, Packer R, et al. Heterogeneity of clinical severity and molecular lesions in Aicardi syndrome. J Pediatr. 1990 Jun. 116(6):911-7. [Medline].

  32. Ohtsuka Y, Oka E, Terasaki T, Ohtahara S. Aicardi syndrome: a longitudinal clinical and electroencephalographic study. Epilepsia. 1993 Jul-Aug. 34(4):627-34. [Medline].

  33. Prats Vinas JM, Martinez Gonzalez MJ, Garcia Ribes A, et al. Callosal agenesis, chorioretinal lacunae, absence of infantile spasms, and normal development: Aicardi syndrome without epilepsy?. Dev Med Child Neurol. 2005 Jun. 47(6):419-20; discussion 364. [Medline].

  34. Rosser T, Acosta M, Packer R. Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females. Pediatr Neurol. 2002 Nov. 27(5):343-6. [Medline].

  35. Sabin A, Feldman H. Chorioretinopathy associated with other evidence of cerebral damage in childhood. J Pediatr. 1949. 35:296-309.

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