Aicardi syndrome is diagnosed in female infants with the clinical association of infantile seizures, mental retardation, agenesis of the corpus callosum, and chorioretinal lacunae.1,2 In addition to the typical chorioretinal lesions, m i crop h th aim i a and other ocular developmental anomalies are observed frequently in Aicardi syndrome.1,2,6,15 Although microphthalmia is a frequent feature in eyes with persistent hyperplastic primary vitreous (PHPV),3-5 the occurrence of PHPV in Aicardi syndrome has not been described to our knowledge. We present a case of PHPV in association with Aicardi syndrome.
A 26-day-old white girl was admitted for evaluation of tonic-clonic seizures beginning 4 days after birth. The girl was a 7 Ib 14 oz product of a normal 41-week gestation with uncomplicated labor and delivery. The patient had no siblings, and there was no family history of primary neurologic disease.
Medical evaluation at the time of admission revealed a well-appearing infant girl with normal clinical neurologic findings, including symmetric reflexes and motor strength of upper and lower extremities. Leukokoria was present in the left eye. No other malformations were noted on physical examination.
Laboratory results, including complete blood count with differential, serum electrolytes and creatinine, and serum liver function studies were all within normal limits except for a mildly elevated bilirubin level. TORCH titers were negative. Chromosome analysis revealed a normal 46,XX karyotype with no recognized microdeletions in the Xp22 region. Electroencephalography demonstrated typical bypsarrhythmia originating in the right occipital cortex and generalizing bilaterally A magnetic resonance imaging scan, with gadolinium, of the brain revealed the absence of the corpus callosum, tissue loss in the left frontal lobe, and hypoplasia of the right temporal and occipital white matter, as well as the presence of porencephalic cysts (Figs LA-BX Microphthalmia of the left eye was noted (Fig 1C). There were no calcifications detected within the eyes or brain.
Ophthalmologic consultation was requested to evaluate leukokoria and corroborate the diagnosis of Aicardi syndrome. On examination, visual acuity was centralsteady-maintained in the right eye and questionable light perception in the left eye. A reverse afferent pupillary defect was present in the left eye. Extraocular motiliiy was full. Intraocular pressure was normal in both eyes. Anterior segment examination was normal in both eyes. Dilated fundus examination in the right eye demonstrated a normal optic disc and vascular architecture. Typical punched-out chorioretinal lacunae without surrounding pigmentation were present inferior to the disc (Fig 2). The retinal periphery was unremarkable. In the left eye, a dense fibrotic retrolental membrane was present. The ciliary processes were adherent to this membrane and were pulled centripetally. B-scan ultrasound in the left eye confirmed the presence of the dense retrolental membrane that extended to, and involved, the posterior retina (Fig 3). There was no calcification or mass present in the choroid or retina. Axial lengths measured by ?-scan ultrasound were 17.9 mm in the right eye and 16.5 mm in the left eye. Electroretinography (ERG) revealed normal ecotopic and photopic responses in the right eye. The ERG in the left eye was extinguished. Visual evoked responses were normal in the right eye and markedly depressed in the left eye.
As first described in 1965, 1 the diagnosis of Aicardi syndrome is based on the clinical association of infantile seizures, mental retardation, absence of the corpus callosum, and the presence of chorioretinal lacunae. Other developmental anomalies are known to occur sporadically in Aicardi syndrome. Skeletal abnormalities, including malformations of the vertebral bodies, are most common. Among these are fused vertebrae, hemivertebrae, variable vertebral size, and spina bifida. Ocular abnormalities, in addition to the typical chorioretinal lacunae, have also been reported. These include colobomas of the optic nerve and choroid, sclera! ectasia, abnormalities of the microscopic retinal architecture, persistent pupillary membrane, and microphthalmia.1,3,6-14 In previous reports, microphthalmia has been observed commonly in association with Aicardi syndrome.6,8,14-25 Despite the recognized association between microphthalmia and PHPV,3'5 neither anterior nor posterior PHPV has been reported in Aicardi syndrome. The presence of optic disc glial tissue15 and retina drawn to the ciliary body14 have also been observed and may, in retrospect, be considered a manifestation of PHPV.
FIGURE 1: (A-C) T1-weighted magnetic resonance images. (A) Sagittal and (B) coronal views showing absence of the corpus callosum. (C) Axial view demonstrating a small left globe with a hyperintense signal in the posterior segment, consistent with PHPV.
FIGURE 2: Fundus photograph of the right eye showing a typical peripapillary "punched out" chorioretinal lacune.
FIGURE 3: B-scan ultrasound demonstrating the presence of a retrolental membrane extending posteriorly to involve the retina.
The systemic and ocular developmental anomalies which appear in Aicardi syndrome are thought to occur between the fourth and twelfth gestational weeks.18,26,27 PHPV is known to be caused by abnormal developmental events occurring between approximately the sixth and ninth weeks of gestation.28,29 It is not surprising that the developmental abnormalities of Aicardi syndrome and PHPV, occurring as they do during the same period of embryogenesis, may give rise to ocular abnormalities with similar features. It is possible that microphthalmia in Aicardi syndrome is a forme fruste of PHPV. Alternatively, the occurrence of PHPV in our patient may be an event that is unrelated to the Aicardi defect. Though figures are not available, PHPV occurs infrequently in the general population. Likewise, Aicardi syndrome is exceedingly rare, occurring in between 1 in 104 and 1 in 105 females.17 The chance occurrence of these two findings in one patient would, therefore, be exceedingly unlikely, but must be considered.
Based on several lines of evidence, Aicardi syndrome is believed to be an X-linked dominant, geneticallydetermined condition with early embryonic lethality in hemizygous males.16 All reported cases of Aicardi syndrome have occurred in females or individuals with additional sex chromosomes (47,XXY male30). One 46,XY male has been reported31; however, the diagnosis of Aicardi syndrome in this patient has been debated based on the appearance of the chorioretinal lesions.32'33 Karyotype analysis typically does not demonstrate chromosomal abnormalities in patients with Aicardi syndrome. However, cytogenetic testing has demonstrated the presence of microdeletions in some cases.19·20 In our patient, chromosomal analysis demonstrated a normal 46,XX female karyotype with no demonstrable Xp22 microdeletion.
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