From Bascom Palmer Eye Institute, Miami, Florida.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Hassan A. Aziz, MD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136.
Aicardi syndrome was historically characterized by the triad features of infantile spasms, agenesis of the corpus callosum, and the distinctive chorioretinal lacunae; however, with new research and case reports it is clear that the syndrome takes account of various additional symptoms. Neurological features may include mental retardation in most of the cases, cortical polymicrogyria, periventricular heterotopia, cysts of the choroid plexus, and a gross asymmetry of the hemispheres. Phenotypical features suggestive of Aicardi syndrome are prominent premaxilla, sparse lateral eyebrows, skin lesions including multiple nevi, skin tags, hemangiomas, one giant melanotic nevus and a history of a removed angiosarcoma, and hand malformations including camptodactyly, proximal placement of the thumb, and hypoplasia of the fifth finger.1 Musculoskeletal signs include missing or bifurcated vertebrae and ribs, which may result in severe scoliosis and thus interfere with the respiratory function. Less typical ophthalmologic features are unilateral microphthalmia or optic nerve colobomas, hypoplasia of the optic nerve, nystagmus, and retinal detachment. In the patient we describe, the right optic nerve is aplastic with severe hypoplasia of the left optic nerve and she had bilateral iris colobomas, both of which are atypical for Aicardi syndrome.
A 1-year-old girl was referred with the diagnosis of bilateral iris and chorioretinal colobomas. The patient was delivered full term by cesarean section after an uneventful pregnancy and weighed 7 pounds 8 ounces. On presentation, she had a whitened red reflex and no visual response to light in either eye. Pupils were 6 mm in both eyes and irregular due to the presence of inferonasal colobomas of the iris bilaterally (Fig. 1). On dilated fundus examination, there were bilateral chorioretinal colobomas. She had high myopia (−12.75 + 0.5 176 in the right eye and −13.23 + 1.75 173 in the left eye) and a wandering nystagmus with a tendency of downward gaze. Krimsky testing revealed a 20-diopter esotropia.
Figure 1. Bilateral Inferonasal Iris Colobomas in a 1-Year-Old Child.
During a follow-up examination 6 months later, the patient presented with rubeosis iridis and retinal detachment in the left eye. An examination under anesthesia was performed where funduscopic images documented large scattered lacunae (Fig. 2). The optic nerve head was aplastic in the right eye, and there was severe hypoplasia of the optic nerve head in the left eye. Ultrasonography was performed and absence of the optic nerve in the right eye and a retinal detachment in the left eye were noted (Fig. 3). Magnetic resonance imaging scans were ordered and showed a hypoplastic corpus callosum (Fig. 4).
Figure 2. Fundus Photographs Showing the Changes in a Patient with Aicardi Syndrome. (A) Lacunae in the Superotemporal and Inferior Aspect of the Left Eye with a Large Coloboma in the Temporal Side and Severe Hypoplasia of the Optic Nerve Head. (B) In the Right Eye, a Large Superior Retinal Detachment Was Noted.
Figure 3. Vertical Axial Length Ultrasound of Both Eyes Showing (A) Absence of the Optic Nerve in the Right Eye and (B) Retinal Detachment Extending from the Lens to the Area of the Optic Disc in the Left Eye.
Figure 4. Magnetic Resonance Imaging T1 Sagittal Cut of the Patient’s Head Showing Hypoplasia of the Corpus Callosum (arrow).
Thus, the diagnosis of atypical Aicardi syndrome was established in the operating room due to the presence of the pathognomonic chorioretinal lacunae. The retinal detachment in the left eye was repaired with scleral buckle, lensectomy, vitrectomy, membrane peel, fluid–air exchange, and silicone oil.
Aicardi syndrome is a clinically diagnosed, X-linked dominant disease. The only two males reported to have the disease were XXY.2 The disease is not mapped on the X chromosome, but is believed to be caused by a sporadic mutation. The prognosis is commonly dim for patients presenting with the typical disease and the mean age of survival is 8.3 years.1 The disease encompasses a broad spectrum of manifestations and the diagnostic criteria are represented in Table 1.3,4
Table 1: Diagnostic Criteria of Aicardi Syndrome
Aicardi syndrome has variable presentation: 5 of 156 patients did not have infantile spasms5 and 6 of 186 patients had normal-looking corpus callosum on imaging6; thus the chorioretinal lacunae are the pathognomic feature of Aicardi syndrome. Despite the punched out appearance, the lacunae are flat lesions of nonpigmented retinal pigment epithelial cells. Their sizes vary greatly from one-tenth of the disc area to several times its diameter. Their size remains unchanged over time, but some pigment deposits may occur in the periphery or even centrally.
Pathologic examination of the lesion shows no evidence of degenerative or inflammatory changes, but rather a thinning of the choroid and the sclera in that area. The overlying retinal pigment epithelium and photoreceptors may show degenerative changes.7–9 A study by Donnenfeld et al. in 1989 of 18 patients investigated the prevalence of ophthalmologic signs in Aicardi syndrome and the results are summarized in Table 2.5 Optic nerve colobomas were commonly unilateral, extended posteriorly with cystic dilation, and some had encircling pigment changes that resembled the “morning glory” phenomenon.
Table 2: Ophthalmic Signs of Aicardi Syndrome
With regard to non-ophthalmologic features, patients with Aicardi syndrome usually present with severe psychomotor retardation. However, recent literature and case reports showed phenotypical disparity in the expression of the disease.10 Grosso et al. described a 9-year-old child with normal cognitive, motor, and language skills who was diagnosed as having Aicardi syndrome.11 Numerous studies aimed to determine prognostic factors of Aicardi syndrome. Better outcome is anticipated in patients with fewer retinal lesions, especially if the lesions are unilateral.2 Cognitive prognosis is worse if the patient’s chorioretinal lacunae are larger than five times the optic nerve head diameter.12 Degree of the corpus callosum maldevelopment is another predictive factor—a greater degree of hypoplasia correlates with a worse outcome.
Based on the presence of the typical chorioretinal lacunae in the right eye and the hypoplasia of the corpus callosum in the current patient, a diagnosis of Aicardi syndrome was made. However, this atypical patient also had undescribed features, bilateral inferonasal iris colobomas, and total absence of the right optic nerve.
- Menezes AV, Enzenauer RW, Buncic JR. Aicardi syndrome: the elusive mild case. Br J Ophthalmol. 1994;78:494–496. doi:10.1136/bjo.78.6.494 [CrossRef]
- Hopkins IJ, Humphrey I, Keith CG, Susman M, Webb GC, Turner EK. The Aicardi syndrome in a 47 XXY male. Aust Paediatr J. 1979;15:278–280.
- Sutton V, Hopkins B, Eble T, Gambhir N, Lewis R. Facial and physical features of Aicardi syndrome: infants to teenagers. Am J Med Genet. 2005;138A:254–258. doi:10.1002/ajmg.a.30963 [CrossRef]
- Aicardi J. Aicardi syndrome: old and new findings. Int Pediatr. 1999;14:5–8.
- Donnenfeld AE, Packer RJ, Zackai EH, Chee CM, Sellinger B, Emmanuel BS. Clinical, cytogenetic, and pedigree findings in 18 cases of Aicardi syndrome. Am J Med Genet. 1989;32:461–467. doi:10.1002/ajmg.1320320405 [CrossRef]
- Aicardi J. Callosal agenesis chorioretinal lacunae, absence of infantile spasms, and normal development: Aicardi syndrome without epilepsy?Dev Med Child Neurol. 2005;47:364. doi:10.1017/S001216220521071X [CrossRef]
- Aicardi J. Aicardi syndrome. Brain Dev. 2005;27:164–171. doi:10.1016/j.braindev.2003.11.011 [CrossRef]
- Hamano S, Yagishita S, Kawakami M, Ito F, Maekawa K. Aicardi syndrome post-mortem findings. Pediatr Neurol. 1989;5:259–261. doi:10.1016/0887-8994(89)90088-X [CrossRef]
- Del Pero RA, Mets MB, Tripathi RC, Torczynski E. Anomalies of retinal architecture in Aicardi syndrome. Arch Ophthalmol. 1986;104:1659–1664.
- Rosser TL, Acosta MT, Packer RJ. Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females. Pediatr Neurol. 2002;27:343–349. doi:10.1016/S0887-8994(02)00450-2 [CrossRef]
- Grosso S, Lasorella G, Russo A, Galluzzi P, Morgese G, Balestri P. Aicardi syndrome with favourable outcome: case report and review. Brain Dev. 2007;29:443–446. doi:10.1016/j.braindev.2006.11.011 [CrossRef]
- Menezes AV, MacGregor DL, Buncic JR. Aicardi syndrome: natural history and possible predictors of severity. Pediatr Neurol. 1994;11:313–318. doi:10.1016/0887-8994(94)90008-6 [CrossRef]
Diagnostic Criteria of Aicardi Syndrome
|Classic triada||Infantile spasms|
|Agenesis of corpus callosum|
|Major characteristics||Cortical malformations|
|Periventricular and subcortical heterotopias|
|Cysts in the area of the third ventricle|
|Choroidal plexus papilloma|
|Optic nerve head hypoplasia and/or coloboma|
|Supporting features||Vertebral and rib abnormalities (severe scoliosis)|
|Gross cerebral asymmetry|
|Vascular malformation and/or malignancy|
Ophthalmic Signs of Aicardi Syndrome
|Optic nerve coloboma||17%|