Aicardi syndrome in a prematurely born baby with retinopathy of prematurity: eye as a window to a systemic pathology

Abstract

Many of the ophthalmic pathologies can co-exist and when taken together can at times give a clue to a life-threatening systemic condition. Presented here is a case of Aicardi syndrome in a prematurely born baby with retinopathy of prematurity. Early diagnosis by the ophthalmologist helped the baby for a timely neurological attention.

Background

Aicardi syndrome has a classical triad of chorioretinal lacuna, infantile spasms and corpus callosum agenesis or dysgenesis. We report the first case of Aicardi syndrome in a premature baby with retinopathy of prematurity (ROP) (Medline search with keywords Aicardi syndrome and retinopathy of prematurity).

Case presentation

A 6-week-old baby girl was brought by the parents for a smaller left eye than the right eye. She was born at 35 weeks of gestational age with a weight of 2050 g at birth and was treated at a neonatal intensive care unit for 1 week. She was on oxygen (unblended and 100%) supplementation for 4 days for respiratory distress. There was no parental consanguinity. Previous paediatrician consultation report showed that she had seizure in the postnatal period.

On examination at 41 weeks of postmenstrual age, there was menace reflex in both eyes. She had right eye preference with 40 prism dioptre of sensory esotropia. Pupil was 2 mm, round, regular and reacting in right eye. Left eye pupil was irregular in shape and was sluggishly reacting to light. Examination under anaesthesia revealed a horizontal corneal diameter and axial length of 10.50–16.58 mm in the right and 8.50–14.26 mm in the left eye, respectively. The right eye anterior segment was unremarkable; the left eye showed iris hypochromia, tunica vasculosa lentis and posterior synechiae. The lens was clear in both the eyes.

The right eye fundus, showed variable-sized discrete loci of depigmentation areas with sharp borders (chorioretinal lacunae) inferonasal to the optic disc and along inferotemporal arcade (figure 1A). The optic disc was unremarkable and retina was attached. Left eye showed large chorioretinal lacunae inferior to optic disc. The retinal blood vessels crossing over the lacunae appeared normal. The optic disc was larger than the right eye, was pushed to the nasal edge of a peripapillary staphyloma and was associated with a temporal retinal fold (figure 1B). The right retina was healthy with vascularisation extending up to zone III. Left eye had a demarcation line in zone III with mild tortuosity of retinal vessels (figure 2) in superotemporal quadrant suggestive of stage 1, zone III, pre-plus ROP. The demarcation line was too peripheral to be imaged with RetCam Shuttle (Clarity Medical Systems, Pleasanton, California, USA).

Figure 1.

Fundus picture of both the eyes as imaged with a paediatric retinal camera. Right eye (A) shows a normal disc, multiple chorioretinal lacunae inferonasal and inferotemporal to the optic disc (white arrows) and attached retina. Left eye (B) shows chorioretinal lacunae (white arrows) inferior to vertically elongated optic disc with peripapillary staphyloma. There is a small retinal fold extending temporally from the temporal edge of optic disc (black arrows).

Figure 2.

Fundus picture of the left eye showing tortuous retinal vessels without dilatation in superotemporal quadrant (white arrows). The demarcation line was too peripheral to be imaged (RetCam Shuttle; Clarity Medical Systems, Pleasanton, California, USA).

Investigations

Ultrasound B-scan of the left eye showed a perioptic hypoechoic space posterior to sclera of dimension 10.8×11.05 mm with dot-like echoes within, suggestive of a retrobulbar cyst (figure 3). MRI of brain and orbit showed corpus callosum agenesis, interventricular cyst, subependymal nodular heterotopia and diffuse bilateral frontal polymicrogyria. On the MRI left orbit, the intraconal retrobulbar cyst was abutting the optic nerve (dimension: 10×10×13 mm) (figure 4).

Figure 3.

B-scan of the left eye showing a hypoechoic space of size 10.8×11.05 mm with low dot-like internal reflectivity suggestive of a retrobulbar cyst.

Figure 4.

MRI shows (A) nodular heterotropia in periventricular region (circled), (B) interventricular cyst (circled), (C–D) retrobulbar cyst (10×10×13 mm) (arrow) and (E) corpus callosum agenesis and bilateral frontal polymicrogyria.

Treatment

Based on the above findings, she was clinically diagnosed a case of Aicardi syndrome with microphthalmos and stage 1, zone III, pre-plus ROP in the left eye. The retinopathy in left eye was observed closely and it regressed spontaneously within a month. A detailed systemic paediatric workup ruled out costovertebral malformation and sleep induced-electroencephalogram (EEG) showed multifocal epileptiform activity predominantly over the right hemisphere. The paediatric neurologist treated her with anti-epileptics for infantile spasms and the baby continues to remain under paediatric neurologist’s care since then.

Discussion

Aicardi syndrome in a premature baby with ROP has been reported for the first time in the literature. Aicardi syndrome is an X-linked dominant disorder and is seen in women exclusively.¹ Diagnosis is made on a triad of lesion: chorioretinal lacunae, infantile spasms and corpus callosum agenesis or dysgenesis.²

Other major criteria (on MRI brain) include: cortical malformations (such as microgyria, periventricular and subcortical heterotopia), cysts around the third ventricle and/or choroid plexuses, papillomas of choroid plexuses and optic nerve colobomas. The supporting criteria include: vertebral abnormalities, microphthalmia, ‘split-brain’ EEG (associated suppression-burst tracing) and gross hemispheric asymmetry. The EEG findings can be characteristic and include dissociated burst suppression or asymmetrical burst suppression pattern in either cerebral hemisphere, as was in the present case. The diagnosis of Aicardi syndrome is made from the presence of all three classical criteria or from a combination of two classical and two other major/supporting criteria.³ The baby described in this report had many major and supporting criteria in addition to the classical triad.

Among the ophthalmic findings, chorioretinal lacunae are the most consistent findings. They appear as well defined, multifocal, pale areas with minimally pigmented borders and are usually clustered around the optic disc. Histologically, the lacunae are usually normal with variable loss of retinal pigment epithelium and choroid. Other reported ocular abnormalities include optic nerve/iris colobomas, microphthalmos, retrobulbar cysts, papillary membrane remnants, iris synechiae (seen in our case), optic disc hypoplasia, optic disc pigmentation, pseudoglioma, retinal detachment, macular scar and cataract.⁴ Many of these ocular changes are non-specific and are quite often seen in ophthalmic practice without any syndromic association.⁵

Chorioretinal lacunae can often be confused with coloboma forma frusta. One might miss this syndromatic association unless these findings are correlated together and a neuroimaging workup is done. While some of the systemic comorbidities like epilepsy and skeletal problems are amenable to treatment,² systemic infections and pulmonary complications can, at times, be life threatening. Estimated survival rates of subjects with Aicardi syndrome range from 76% by age 6 years and 40% by age 15 years.⁶ Hence, an early diagnosis and treatment with a neurologist helps.

Learning points.

• Aicardi syndrome is an X-linked dominant disorder and is seen in women exclusively.

• Diagnosis depends on the presence of a triad of chorioretinal lacunae, infantile spasms and corpus callosum agenesis or dysgenesis.

• Among the ophthalmic findings, chorioretinal lacunae are the most consistent findings.

• Early diagnosis by the ophthalmologists helps the babies for a timely neurological attention.