INTRODUCTION
Aicardi syndrome (AS) was first reported in 1965 by Jean Aicardi et al.[1] and occurs only in females or heterozygous males with XXY.
The disease is thought to be an X-linked dominant disorder seen sporadically. The exact mutation or candidate gene has not been identified so far. Mutation in TEAD 1 gene is thought to be responsible based on certain studies.[2] Diagnosis is based on Sutton’s modified diagnostic criteria. The diagnosis is confirmed if all the features of classic triad are present namely infantile spasms, chorioretinal lacunae, and partial or total corpus callosal agenesis (CCA). The diagnosis is suspicious if two classic features are present along with two major or supporting features.
The major features are hypoplastic or colobomatous optic disc, cysts around third ventricle or choroid plexus cyst, cortical malformations (most commonly polymicrogyria), and periventricular heterotropia. The supporting features include microphthalmia, vertebral or rib anomalies (most commonly scoliosis), split brain electroencephalogram (EEG), vascular malformation or malignancy, and gross cerebral hemispheric asymmetry. Chorioretinal lacunae was the most consistent feature of the disease.[3]
CASE REPORT
A three-year-old girl, first child of nonconsanguineous parents was referred for ocular examination. She was born preterm at 33 weeks with a birthweight of 2,500 grams. She had refractory seizures from third day of life, poorly controlled with antiepileptics. Predominant seizure type was infantile spasm. She had global developmental delay with right hemiparesis and a developmental quotient of 30%.
On ocular examination, she was having poor fixation and following of light with left esotropia. Anterior segment examination was normal in both eyes. Atropine refraction showed + 2.50 D in vertical and horizontal meridia in both eyes suggestive of absence of a significant refractive error.
Fundus examination was normal in the right eye [Figure 1a]. Left eye showed hypoplastic optic disc. There were multiple yellow white chorioretinal lesions with pigmented borders suggestive of chorioretinal lacunae involving the posterior pole and macula [Figure 1b].
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Figure 1: Shows original fundus images captured with Retcam 3nethra neo. (a) showing normal fundus of right eye with normal optic disc (white arrow) and (b) showing hypoplastic disc in left eye (white arrow) with multiple chorioretinal lacunae (black arrows)
Magnetic resonance imaging brain showed CCA, asymmetric enlargement of right cerebral hemisphere and lateral ventricle with colpocephaly (prominent occipital horns of lateral ventricle), interhemispheric cyst, choroid plexus cyst, and nodular heterotropia in right frontal horn margin [Figure 2].
Figure 2: Original axial T2 weighted MRI brain images with yellow arrow showing asymmetrically enlarged right lateral ventricle with colpocephaly, blue arrow showing interhemispheric cyst, and green arrow showing posterior horn of left lateral ventricle
Magnetic resonance imaging orbit was normal.
EEG showed a recurrent burst of right hemispheric spike and wave discharges with high amplitude. Slow waves with an infrequent burst suppression pattern also noted.
As all the criteria of classic triad were met, along with two major features, a clinical diagnosis of AS was made.
Genetic analysis (whole exome sequencing) was done at 3 months of age which was normal.
She was advised to continue antiepileptics along with physiotherapy and occupational therapy and kept under follow-up. Parents were counselled regarding the prognosis and genetic counselling was done.
DISCUSSION
AS occurs in roughly 1 in 1,00,000 live births. The exact prevalence is not known. Parent-to-child transmission is not reported in AS and the risk in sibling is thought to be less than 0.1%.[3]
The diagnosis is purely clinical and ocular features are a key to it. The pathognomonic feature in AS is the presence of chorioretinal lacunae. These are circumscribed yellow white pale areas with hyperpigmented borders involving the retinal pigment epithelium (RPE) and the choroid. Overlying sensory retina can be intact or absent. The lesions can be unilateral or bilateral and occur in the posterior pole, most notably in the peripapillary area.[4]
Other ocular features reported are optic nerve hypoplasia, optic disc coloboma, papilla nigra, glial proliferation, microphthalmia, and pseudoadenomatous proliferation of RPE.[4]
Late onset retinoblastoma was reported in a 16-year-old girl with AS.[5]
Once the diagnosis is made, the aim is to control the refractory infantile spasms, prevention of aspiration pneumonia, and scoliosis-related complications. The rehabilitation is done with physical, occupational, and speech therapy.[3]
The age of survival in individuals with AS depends on the severity of seizures, aspiration pneumonia, and malignancies. Malignant tumors reported in AS are retinoblastoma, hepatoblastoma, embryonal carcinoma, teratomas, angiosarcoma, and medulloblastoma.[6] The average age of survival ranges from 8 to 32 years as per various studies.[3,7]
This case was reported to increase the awareness about this rare disease, its ocular features, clinical profile, and management.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
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Aicardi syndrome. Brain Dev 2005;27:164–71.
2. Schrauwen I, Szelinger S, Siniard AL, Corneveaux JJ, Kurdoglu A, Richholt R, et al., Ade novo mutation in TEAD1 causes non-x-linked
Aicardi syndrome. Invest Ophthalmol Vis Sci 2015;56:3896–904.
3. Sutton VR, Van den Veyver IB,
Aicardi syndrome Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al. Gene Reviews® Seattle (WA) University of Washington, Seattle 2006 1993–2022.
4. Fruhman G, Eble TN, Gambhir N, Sutton VR, Van den Veyver IB, Lewis RA, Ophthalmologic findings in
Aicardi syndrome. J AAPOS 2012;16:238–41.
5. Akinfenwa PY, Chévez-Barrios P, Harper CA, Gombos DS, Late presentation of retinoblastoma in a teen with
Aicardi syndrome. Ocul Oncol Pathol 2016;2:181–4.
6. Tanaka T, Takakura H, Takashima S, Kodama T, Hasegawa H, A rare case of
Aicardi syndrome with severe brain malformation and hepatoblastoma. Brain Dev 1985;7:507–12.
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Aicardi syndrome from 408 cases. J Child Neurol 2008;23:531–5.
