From the Sisli Etfal Education and Research Hospital, Eye Clinic, Istanbul, Turkey.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Gokhan Gulkilik, MD, Naima Sok. Canik Yali B-1 D:4, Yesilkoy-Istanbul, Turkey.
Joubert syndrome is a rare, autosomal recessive disorder that was first described by Joubert et al. in 1969 and is characterized by episodes of abnormal respiratory pattern, oculomotor findings, hypotonia, ataxia, and developmental retardation with evidence of neuropathologic abnormalities of the cerebellum and brainstem.1 Neuroradiologic findings that confirm the diagnosis include dysgenesis of the cerebellar vermis and hypoplasia of the brainstem.2 Thick and horizontally oriented superior cerebellar peduncles form the classic “molar tooth sign,” which is virtually diagnostic of Joubert syndrome and can be demonstrated in axial images at the level of the midbrain.3
Ophthalmic features described previously include nystagmus, ptosis, strabismus, findings of retinal dystrophy, optic nerve dysplasia, and subnormal electrophysiologic findings.3–7 To our knowledge, a case of Joubert syndrome with ocular neovascularization has not been described previously. In this study, we present a case of Joubert syndrome with features of ocular neovascularization.
A 12-year-old boy diagnosed as having Joubert syndrome was referred to our retina clinic for ophthalmic examination. He was the fourth child of a second-degree consanguineous marriage. The medical histories of his siblings were noncontributory. His parents stated that he had no respiratory problems, but had motor and mental retardation, abnormal eye movements, and ataxic movements since birth. He was taking anti-hypertensive drugs to control systemic hypertension. He was also receiving peritoneal dialysis treatment due to chronic renal failure. Magnetic resonance imaging revealed the diagnostic molar tooth sign in axial scans, and superior and inferior vermian structures were aplasic (Fig. 1). Both kidneys were found to be smaller than normal on abdominal ultrasonography.
Figure 1. T1-Weighted Axial Magnetic Resonance Imaging Image Showing the Classic Molar Tooth Sign.
Informed consent was obtained from the parents. The patient underwent full ophthalmologic examination including visual acuity testing, biomicroscopy, and intraocular pressure measurement after approval from the institutional ethics committee was obtained. The posterior segment was evaluated by indirect ophthalmoscopy with fundus photography and fundus fluorescein angiography. Electroretinography (ERG) and flash visual-evoked potentials (VEP) were performed for evaluation of optic nerve and retinal function. On examination, the patient had bilateral horizontal nystagmus and pupil reactions were normal with no afferent pupil defect. His visual acuities, as allowed by patient cooperation, were hand motions and counting fingers at 1 meter in the right and left eyes, respectively. Intraocular pressure was 50 mm Hg in the right eye and 15 mm Hg in the left eye. Biomicroscopic examination of the right eye revealed a normal cornea and lens, but there was neovascularization on the pupillary border and over the iris. Anterior segment structures were normal in the left eye. Dilated fundus examination revealed intravitreal hemorrhage in the right eye, and the optic nerve heads were atrophic and pale in both eyes. Both retinas were dystrophic with pigmentary changes and the retinal vasculatures were attenuated with decreased vessel caliber (Fig. 2). Iris fluorescein angiography showed pathologic vessels in the right eye. There were ischemic areas and significant fluorescein leakage due to retinal neovascularization. The left eye also showed ischemic areas but less fluorescein leakage with only a few focal neovascularizations in the left eye (Fig. 3). ERG revealed low amplitudes with normal latency, and b/a ratios were decreased. Flash VEP was normal in the left eye, but P2 latency in the right eye was delayed.
Figure 2. Color Fundus Image Showing Pigmentary Retinal Dystrophy with Attenuated Vessels.
Figure 3. Multiple Window Defects over the Entire Fundus and a Small Neovascularization with Leakage on Fundus Fluorescein Angiography in the Left Eye.
Joubert syndrome is an autosomal recessive disease that primarily affects the balance and coordination centers of the central nervous system. Diagnosis can be made by history of developmental delay, abnormal eye movements, and abnormal breathing together with neuroradiologic findings of dysplastic midbrain structures and complete or partial absence of the cerebellar vermis.8 Joubert syndrome can be classified into two groups according to the presence or absence of retinal dystrophy.9
Ophthalmic findings that have been reported to occur in Joubert syndrome are ptosis, nystagmus, strabismus, retinal dystrophy with pigmentary mottling, optic nerve dysplasia, chorioretinal coloboma, and impaired vestibulo-ocular reflex.3–7 Nystagmus is also a common feature usually present at birth. Khan et al.7 reported a series of eight cases of Joubert syndrome, five having nystagmus at the primary position. They stated that other than sensory causes, nystagmus can also be neurologic due to structural abnormalities in Joubert syndrome Retinal pigmentary dystrophy with subnormal or flat ERG was commonly reported in Joubert syndrome, and some patients may suffer from congenital blindness.2,4,7 In patients with retinal dystrophy, prognosis is worse because the patients are prone to multicystic renal disease.
In the current case, the patient had horizontal nystagmus in the primary position since birth. He had pigmentary retinal dystrophy with attenuated caliber of the retinal vasculature and low amplitudes on ERG and low b/a ratios. The flash VEP was asymmetric and abnormal in the right eye. Khan et al.7 stated that asymmetric flash VEP and see-saw nystagmus can be attributed to abnormal chiasmal decussation and impaired axonal guidance. The current findings are consistent with those of previous studies.
Narrowing of the retinal vessels in retinitis pigmentosa is suggested to be secondary to degeneration of photoreceptors leading to increased oxygen tension in the retina. This may cause retinal capillary degeneration and capillary nonperfusion. Such capillary nonperfusion with associated ischemia is proposed to be the stimulus for retinal neovascularization in retinitis pigmentosa.10 A similar mechanism may explain the etiology of the neovascularization in the current case. The decreased b/a ratio observed on ERG, which also occurs in ischemic retinal vein occlusions, is evidence of retinal ischemia. Neovascularization in the anterior segment is the most severe and may be related to the chronicity of the disease. Also, ischemia may be caused or worsened by complications of systemic hypertension or chronic renal failure. This is the first case in the literature that describes signs of ocular neovascularization in Joubert syndrome.
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- Shen WC, Shian WJ, Chen CC, Chi CS, Lee SK, Lee KR. MRI of Joubert’s syndrome. Eur J Radiol. 1994;18:30–33. doi:10.1016/0720-048X(94)90361-1 [CrossRef]
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- Uliss AE, Gregor ZJ, Bird AC. Retinitis pigmentosa and retinal neovascularization. Ophthalmology. 1986;93:1599–1603.